{"id":1320,"date":"2018-11-28T17:16:42","date_gmt":"2018-11-28T17:16:42","guid":{"rendered":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/?post_type=chapter&#038;p=1320"},"modified":"2019-01-08T15:30:33","modified_gmt":"2019-01-08T15:30:33","slug":"20-3-addition-of-rmgx-rli-to-co","status":"publish","type":"chapter","link":"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry2\/chapter\/20-3-addition-of-rmgx-rli-to-co\/","title":{"raw":"20.3. Addition of RMgX\/RLi to polar pi bonds","rendered":"20.3. Addition of RMgX\/RLi to polar pi bonds"},"content":{"raw":"<article id=\"elm-main-content\" class=\"elm-content-container\">\r\n<h2 class=\"mt-content-container\">20.3.1. A digression: Formation and properties of organometallic reagents<\/h2>\r\nThe <a title=\"Group 1: The Alkali Metals\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Inorganic_Chemistry\/Supplemental_Modules_(Inorganic_Chemistry)\/Descriptive_Chemistry\/Elements_Organized_by_Block\/1_s-Block_Elements\/Group__1%3A_The_Alkali_Metals\" rel=\"internal\">alkali metals<\/a> (Li, Na, K etc.) and the <a title=\"Group 2 Elements: The Alkaline Earth Metals\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Inorganic_Chemistry\/Supplemental_Modules_(Inorganic_Chemistry)\/Descriptive_Chemistry\/Elements_Organized_by_Block\/1_s-Block_Elements\/Group__2_Elements%3A_The_Alkaline_Earth_Metals\" rel=\"internal\">alkaline earth metals<\/a> (Mg and Ca, together with Zn) are good reducing agents, the former being stronger than the latter. These same metals reduce the carbon-halogen bonds of alkyl halides. The halogen is converted to a halide anion, and the carbon bonds to the metal which has characteristics similar to a <a title=\"Carbanions\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Supplemental_Modules_(Organic_Chemistry)\/Fundamentals\/Reactive_Intermediates\/Carbanions\" rel=\"internal\">carbanion <\/a>(R:-).\r\n<div id=\"section_1\" class=\"mt-section\">\r\n<h3 class=\"editable\">Formation of organometallic reagents<\/h3>\r\nMany organometallic reagents are commercially available, however, it is often necessary to make then. The following equations illustrate these reactions for the commonly used metals lithium and magnesium (R may be hydrogen or alkyl groups in any combination).\r\n<ul>\r\n \t<li>\r\n<h3>An alkyllithium reagent<\/h3>\r\n<\/li>\r\n<\/ul>\r\n<p style=\"text-align: center\"><span id=\"MathJax-Span-9\" class=\"msubsup\"><span id=\"MathJax-Span-10\" class=\"mtext\">R<sub>3<\/sub><\/span><span id=\"MathJax-Span-11\" class=\"texatom\"><span id=\"MathJax-Span-12\" class=\"mrow\"><span id=\"MathJax-Span-13\" class=\"mspace\"><\/span><\/span><\/span><\/span><span id=\"MathJax-Span-17\" class=\"mtext\">C<\/span><span id=\"MathJax-Span-18\" class=\"texatom\"><span id=\"MathJax-Span-19\" class=\"mrow\"><span id=\"MathJax-Span-20\" class=\"mo\">\u2212<\/span><\/span><\/span><span id=\"MathJax-Span-21\" class=\"mtext\">X<\/span><span id=\"MathJax-Span-22\" class=\"mo\">+<\/span><span id=\"MathJax-Span-23\" class=\"mn\">2<\/span><span id=\"MathJax-Span-24\" class=\"mspace\"><\/span><span id=\"MathJax-Span-25\" class=\"mtext\">Li<\/span><span id=\"MathJax-Span-26\" class=\"mo\">\u2192<\/span><span id=\"MathJax-Span-27\" class=\"msubsup\"><span id=\"MathJax-Span-28\" class=\"mtext\">R<\/span><span id=\"MathJax-Span-29\" class=\"texatom\"><span id=\"MathJax-Span-30\" class=\"mrow\"><span id=\"MathJax-Span-31\" class=\"mspace\"><\/span><\/span><\/span><sub><span id=\"MathJax-Span-32\" class=\"texatom\"><span id=\"MathJax-Span-33\" class=\"mrow\"><span id=\"MathJax-Span-34\" class=\"mn\">3<\/span><\/span><\/span><\/sub><\/span><span id=\"MathJax-Span-35\" class=\"mtext\">C<\/span><span id=\"MathJax-Span-36\" class=\"texatom\"><span id=\"MathJax-Span-37\" class=\"mrow\"><span id=\"MathJax-Span-38\" class=\"mo\">\u2212<\/span><\/span><\/span><span id=\"MathJax-Span-39\" class=\"mtext\">Li<\/span><span id=\"MathJax-Span-40\" class=\"mo\">+<\/span><span id=\"MathJax-Span-41\" class=\"mtext\">LiX<\/span><\/p>\r\n\r\n<ul>\r\n \t<li>\r\n<h3>A Grignard reagent<\/h3>\r\n<\/li>\r\n<\/ul>\r\n<p style=\"text-align: center\"><span id=\"MathJax-Span-50\" class=\"msubsup\"><span id=\"MathJax-Span-51\" class=\"mtext\">R<\/span><span id=\"MathJax-Span-52\" class=\"texatom\"><span id=\"MathJax-Span-53\" class=\"mrow\"><span id=\"MathJax-Span-54\" class=\"mspace\"><\/span><\/span><\/span><sub><span id=\"MathJax-Span-55\" class=\"texatom\"><span id=\"MathJax-Span-56\" class=\"mrow\"><span id=\"MathJax-Span-57\" class=\"mn\">3<\/span><\/span><\/span><\/sub><\/span><span id=\"MathJax-Span-58\" class=\"mtext\">C<\/span><span id=\"MathJax-Span-59\" class=\"texatom\"><span id=\"MathJax-Span-60\" class=\"mrow\"><span id=\"MathJax-Span-61\" class=\"mo\">\u2212<\/span><\/span><\/span><span id=\"MathJax-Span-62\" class=\"mtext\">X<\/span><span id=\"MathJax-Span-63\" class=\"mo\">+<\/span><span id=\"MathJax-Span-64\" class=\"mtext\">Mg<\/span><span id=\"MathJax-Span-65\" class=\"mo\">\u2192<\/span><span id=\"MathJax-Span-66\" class=\"msubsup\"><span id=\"MathJax-Span-67\" class=\"mtext\">R<\/span><span id=\"MathJax-Span-68\" class=\"texatom\"><span id=\"MathJax-Span-69\" class=\"mrow\"><span id=\"MathJax-Span-70\" class=\"mspace\"><\/span><\/span><\/span><sub><span id=\"MathJax-Span-71\" class=\"texatom\"><span id=\"MathJax-Span-72\" class=\"mrow\"><span id=\"MathJax-Span-73\" class=\"mn\">3<\/span><\/span><\/span><\/sub><\/span><span id=\"MathJax-Span-74\" class=\"mtext\">C<\/span><span id=\"MathJax-Span-75\" class=\"texatom\"><span id=\"MathJax-Span-76\" class=\"mrow\"><span id=\"MathJax-Span-77\" class=\"mo\">\u2212<\/span><\/span><\/span><span id=\"MathJax-Span-78\" class=\"mtext\">MgX<\/span><\/p>\r\nHalide reactivity in these reactions increases in the order: Cl &lt; Br &lt; I and fluorides are usually not used. The alkyl magnesium halides described in the second reaction are called Grignard reagents after the French chemist, Victor Grignard, who discovered them and received the Nobel prize in 1912 for this work. The other metals mentioned above react in a similar manner, but Grignard and Alkyllithium reagents are the most widely used. Although the formulae drawn here for the alkyllithium and Grignard reagents reflect the stoichiometry of the reactions and are widely used in the chemical literature, they do not accurately depict the structural nature of these remarkable substances. Mixtures of polymeric and other associated and complexed species are in equilibrium under the conditions normally used for their preparation.\r\n\r\nA suitable solvent must be used. For alkyllithium formation pentane or hexane is usually used. Diethyl ether can also be used but the subsequent alkyllithium reagent must be used immediately after preparation due to an interaction with the solvent. Ethyl ether or THF are essential for Grignard reagent formation. Lone pair electrons from two ether molecules form a complex with the magnesium in the Grignard reagent (As pictured below). This complex helps stabilize the organometallic and increases its ability to react.\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170011\/3.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image006.png\" width=\"198\" height=\"189\" \/>\r\n\r\nThese reactions are obviously substitution reactions, but they cannot be classified as nucleophilic substitutions, as were the earlier reactions of alkyl halides. Because the functional carbon atom has been reduced, the polarity of the resulting functional group is inverted (an originally electrophilic carbon becomes nucleophilic). This change, shown below, makes alkyl lithium and Grignard reagents excellent nucleophiles and useful reactants in synthesis.\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170013\/4.jpg\" alt=\"http:\/\/www2.chemistry.msu.edu\/faculty\/reusch\/VirtTxtJml\/Images2\/fncpolar.gif\" width=\"321\" height=\"211\" \/>\r\n<div>\r\n<div id=\"example\">\r\n<div class=\"textbox examples\">\r\n<h3>Examples<\/h3>\r\n<div id=\"section_1\" class=\"mt-section\">\r\n<div id=\"example\">\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170016\/5.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image010.png\" width=\"418\" height=\"91\" \/>\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170018\/6.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image012.png\" width=\"360\" height=\"95\" \/>\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<div id=\"section_2\" class=\"mt-section\">\r\n<h3 class=\"editable\">Common organometallic reagents<\/h3>\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170020\/7.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image014.png\" width=\"489\" height=\"115\" \/>\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170023\/8.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image016.png\" width=\"380\" height=\"109\" \/>\r\n<div id=\"section_5\" class=\"mt-section\">\r\n<h3 class=\"editable\">Organometallic reagents as bases<\/h3>\r\nThese reagents are very strong bases (pKa's of saturated hydrocarbons range are around 50). Although not usually done with Grignard reagents, organolithium reagents can be used as strong bases. Both Grignard reagents and organolithium reagents react with water to form the corresponding hydrocarbon. This is why so much care is needed to insure dry glassware and solvents when working with organometallic reagents.\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170048\/18.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image036.png\" width=\"551\" height=\"89\" \/>\r\n\r\nIn fact, the reaction of Grignard reagents and organolithium reagents with water can be exploited to convert alkyl halides into the corresponding hydrocarbon (illustrated below). The halogen is converted to an organometallic reagent and then subsequently reacted with water to form an alkane.\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170050\/19.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image038.png\" width=\"319\" height=\"94\" \/>\r\n\r\n<\/div>\r\n<div id=\"section_6\" class=\"mt-section\">\r\n<h3 class=\"editable\">Limitation of organometallic reagents<\/h3>\r\nAs discussed above, Grignard and organolithium reagents are powerful bases. Because of this they cannot be used as nucleophiles on compounds which contain acidic hydrogens.\u00a0 If they are used they will act as a base and deprotonate the acidic hydrogen rather than act as a nucleophile and attack the carbonyl.\u00a0 A partial list of functional groups which cannot be used are: alcohols, amides, 1<sup>o<\/sup> amines (RNH<sub>2<\/sub>), 2<sup>o<\/sup> amines (R<sub>2<\/sub>NH), carboxylic acids, and terminal alkynes.\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170052\/20.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image040.png\" \/>\r\n<h3>Video<\/h3>\r\nhttps:\/\/youtu.be\/3FRV31YYtL8\r\n\r\n<img class=\"alignnone size-thumbnail wp-image-3006\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/08152802\/frame-37-150x150.png\" alt=\"\" width=\"150\" height=\"150\" \/>\r\n\r\n<\/div>\r\n<\/div>\r\n<div id=\"section_3\" class=\"mt-section\">\r\n<h2 class=\"editable\">20.3.2. Reaction of organometallic reagents with polar bonds<\/h2>\r\nBoth 'Grignard reagents' and organolithiums are particularly useful in nucleophilic addition reactions with carbonyl electrophiles, such as ketones:\r\n\r\n<img class=\"\u201cinternal internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28171232\/image139.png\" alt=\"image140.png\" width=\"755px\" height=\"95px\" \/>\r\n\r\nThe nucleophilic carbon need not be primary as in the picture above.\u00a0 The synthesis of 2-phenyl-2-propanol,\u00a0 for example, can be carried by reacting phenylmagnesium bromide with acetone.\r\n\r\n<img class=\"\u201cinternal internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28171236\/image141.png\" alt=\"image142.png\" width=\"676px\" height=\"111px\" \/>\r\n\r\nAddition to formaldehyde gives 1<sup>o<\/sup> alcohols\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170027\/10.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image020.png\" width=\"343\" height=\"117\" \/>\r\n\r\nAddition to aldehydes gives 2<sup>o<\/sup> alcohols\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170030\/11.jpg\" alt=\"11.jpg\" width=\"340\" height=\"117\" \/>\r\n\r\nAddition to ketones gives 3<sup>o<\/sup> alcohols\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170032\/12.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image024.png\" width=\"327\" height=\"114\" \/>\r\n<h3>Reaction of organometallic reagents with carbon dioxide: Synthesis of carboxylic acids<\/h3>\r\nGrignard reagents can be also be carboxylated simply by pouring the organic solution over dry ice (solid CO<sub>2<\/sub>), then adding aqueous HCl:\r\n\r\n<img class=\"\u201cinternal internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28171239\/image143.png\" alt=\"image144.png\" width=\"379px\" height=\"105px\" \/>\r\n\r\nOr in general:\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170034\/13.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image026.png\" width=\"355\" height=\"125\" \/>\r\n<div>\r\n<div class=\"textbox examples\">\r\n<h3>Examples<\/h3>\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170037\/14.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image028.png\" width=\"519\" height=\"677\" \/>\r\n\r\n<\/div>\r\n<\/div>\r\nGoing from reactants to products simplified\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170039\/15.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image030.png\" \/>\r\n\r\n<\/div>\r\n<div id=\"section_4\" class=\"mt-section\">\r\n<h3 class=\"editable\">Mechanism for the addition to carbonyls<\/h3>\r\nThe mechanism for a Grignard agent is shown.\u00a0 The mechanism for an organolithium reagent is essentially the same.\r\n\r\n1)\u00a0 Nucleophilic attack\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170043\/16.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image032.png\" width=\"291\" height=\"126\" \/>\r\n\r\n2) Protonation\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170045\/17.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image034.png\" width=\"489\" height=\"130\" \/>\r\n\r\n<\/div>\r\n<div id=\"section_7\" class=\"mt-section\">\r\n<div class=\"textbox examples\">\r\n<div id=\"section_7\" class=\"mt-section\">\r\n<h3 class=\"editable\">Problems<\/h3>\r\n1) Please write the product of the following reactions.\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170055\/21.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image042.png\" width=\"484\" height=\"525\" \/>\r\n\r\n2) Please indicate the starting material required to produce the product.\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170057\/22.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image044.png\" width=\"472\" height=\"462\" \/>\r\n\r\n3) Please give a detailed mechanism and the final product of this reaction\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170100\/23.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image046.png\" \/>\r\n\r\n4)\u00a0 Please show two sets of reactants which could be used to synthesize the following molecule using a Grignard reaction.\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170102\/24.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image048.png\" width=\"163\" height=\"102\" \/>\r\n\r\n&nbsp;\r\n\r\n<\/div>\r\n<div id=\"section_8\" class=\"mt-section\">\r\n<h3 class=\"editable\">Answers<\/h3>\r\n[reveal-answer q=\"336398\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"336398\"\r\n\r\n1)\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170104\/25.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image050.png\" width=\"441\" height=\"343\" \/>\r\n\r\n2)\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170106\/26.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image052.png\" width=\"536\" height=\"148\" \/>\r\n\r\n3)\r\n\r\nNucleophilic attack\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170109\/27.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image054.png\" width=\"438\" height=\"129\" \/>\r\n\r\nProtonation\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170112\/28.jpg\" alt=\"28.jpg\" width=\"476\" height=\"105\" \/>\r\n\r\n4)\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170114\/29.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image058.png\" width=\"552\" height=\"212\" \/>[\/hidden-answer]\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<div id=\"section_9\" class=\"mt-section\">\r\n<h4 class=\"editable\">Contributors<\/h4>\r\n<ul>\r\n \t<li><a class=\"external\" title=\"http:\/\/science.athabascau.ca\/staff-pages\/dietmark\" href=\"http:\/\/science.athabascau.ca\/staff-pages\/dietmark\" target=\"_blank\" rel=\"external nofollow noopener\">Dr. Dietmar Kennepohl<\/a> FCIC (Professor of Chemistry, <a class=\"external\" title=\"http:\/\/www.athabascau.ca\/\" href=\"http:\/\/www.athabascau.ca\/\" target=\"_blank\" rel=\"external nofollow noopener\">Athabasca University<\/a>)<\/li>\r\n \t<li>Prof. Steven Farmer (<a class=\"external\" title=\"http:\/\/www.sonoma.edu\" href=\"http:\/\/www.sonoma.edu\" target=\"_blank\" rel=\"external nofollow noopener\">Sonoma State University<\/a>)<\/li>\r\n<\/ul>\r\n<header><\/header><\/div>\r\n<\/article>\r\n<div id=\"section_9\" class=\"mt-section\"><header><\/header><section class=\"mt-content-container\">\r\n<div id=\"section_6\" class=\"mt-section\"><section class=\"mt-content-container\">\r\n<h3 id=\"note\">Reaction with esters<\/h3>\r\n<div id=\"section_1\" class=\"mt-section\">\r\n\r\nEsters and acid chlorides will react with <em>two<\/em> molar equivalents of Grignard reagent:\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28171244\/image148.png\" alt=\"image148.png\" width=\"578px\" height=\"350px\" \/>\r\n\r\nThe first reaction is an acyl substitution reaction, and the second is a nucleophilic carbonyl addition. Because ketones and aldehydes are better electrophiles than carboxylic acid derivatives, it is not possible to stop these reactions at the ketone\/aldehyde stage.\r\n\r\nIn general, we see the attachment of <strong>two identical R' groups<\/strong> from the organometallic in the alcohol product:\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170719\/1.jpg\" alt=\"File:\/C:\\Users\\Gantor\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image002.png\" \/>\r\n\r\nCarboxylic acids and amides will simply protonate the Grignard reagent, not a terribly productive reaction.\r\n\r\n<\/div>\r\n<div id=\"section_2\" class=\"mt-section\">\r\n<div>\r\n<div class=\"textbox examples\">\r\n<h3>Examples<\/h3>\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170721\/2.jpg\" alt=\"2.jpg\" \/>\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<div id=\"section_4\" class=\"mt-section\">\r\n<div class=\"textbox exercises\">\r\n<h3>Exercises<\/h3>\r\n<div id=\"section_4\" class=\"mt-section\">\r\n<div id=\"s61700\" class=\"mt-include\">\r\n<div id=\"section_15\" class=\"mt-section\">\r\n\r\n<strong>1.<\/strong>\r\n\r\nIf allylmagnesium\u00a0chloride (CH<sub>2<\/sub>=CH=CH<sub>2<\/sub>MgCl) were added to a solution of the following compound and then worked-up with acid, the product would contain a chiral center.\u00a0Would the product be a racemic mixture (optically inactive) or an enantiomerically pure product (optically active)? Draw both enantiomers.\r\n\r\n<img class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170725\/17.24q.png\" alt=\"\" width=\"144px\" height=\"138px\" \/>\r\n\r\n<strong>2.<\/strong>\r\n\r\nWhat combination of carbonyl compound and Grignard\u00a0(use MgBr)\u00a0reagent would yield the following alcohols (after workup)?\r\n\r\n(a)\u00a0<img class=\"internal\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170726\/17.30aq.png\" alt=\"\" width=\"100\" height=\"116\" \/>\u00a0\u00a0 \u00a0 (b)\u00a0<img class=\"internal\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170727\/17.30bq.png\" alt=\"\" width=\"141\" height=\"63\" \/>\u00a0\u00a0 \u00a0 (c)\u00a0<img class=\"internal\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170729\/17.30cq.png\" alt=\"\" width=\"114\" height=\"94\" \/>\u00a0\u00a0 \u00a0 (d)\u00a0<img class=\"internal\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170730\/17.30dq.png\" alt=\"\" width=\"139\" height=\"98\" \/>\r\n\r\n&nbsp;\r\n\r\n<\/div>\r\n<div id=\"section_16\" class=\"mt-section\">\r\n<h3 id=\"Solutions-61700\">Solutions<\/h3>\r\n[reveal-answer q=\"317037\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"317037\"]\r\n\r\n<strong>1.<\/strong>\r\n\r\nThe result would be a racemic mixture of the following.\r\n\r\n<img class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170736\/17.24a.png\" alt=\"\" width=\"343px\" height=\"150px\" \/>\r\n\r\n<strong>2.<\/strong>\r\n\r\n(a)\u00a0<img class=\"internal\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170738\/17.30aa.png\" alt=\"\" width=\"314\" height=\"71\" \/>\u00a0\u00a0 \u00a0 (b)\u00a0\u00a0<img class=\"internal\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170740\/17.30ba..png\" alt=\"\" width=\"252\" height=\"72\" \/>\u00a0 \u00a0 (c)\u00a0<img class=\"internal\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170743\/17.30ca.png\" alt=\"\" width=\"225\" height=\"70\" \/>\r\n\r\n(d)\u00a0<img class=\"internal\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170745\/17.30da.png\" alt=\"\" width=\"248\" height=\"77\" \/>\r\n\r\n[\/hidden-answer]\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<h4 class=\"editable\">Contributors<\/h4>\r\n<\/div>\r\n<div id=\"section_5\" class=\"mt-section\">\r\n<ul>\r\n \t<li><a class=\"external\" title=\"http:\/\/science.athabascau.ca\/staff-pages\/dietmark\" href=\"http:\/\/science.athabascau.ca\/staff-pages\/dietmark\" target=\"_blank\" rel=\"external nofollow noopener\">Dr. Dietmar Kennepohl<\/a> FCIC (Professor of Chemistry, <a class=\"external\" title=\"http:\/\/www.athabascau.ca\/\" href=\"http:\/\/www.athabascau.ca\/\" target=\"_blank\" rel=\"external nofollow noopener\">Athabasca University<\/a>)<\/li>\r\n \t<li>Prof. Steven Farmer (<a class=\"external\" title=\"http:\/\/www.sonoma.edu\" href=\"http:\/\/www.sonoma.edu\" target=\"_blank\" rel=\"external nofollow noopener\">Sonoma State University<\/a>)<\/li>\r\n<\/ul>\r\n<header>\r\n<h3>Reaction of organometallics with epoxides<\/h3>\r\nGrignard and organolithium reagents will also react with epoxides, attacking the less hindered carbon (as expected for basic\/nucleophilic ring-opening conditions \u2013 see <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-6-epoxide-reactions\/\">section 9.6<\/a>).\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28171241\/image145.png\" alt=\"image145.png\" width=\"463px\" height=\"122px\" \/>\r\n\r\nBeing a strong nucleophile, the organometallic attacks the epoxide from the less hindered end of the epoxide ring.\u00a0 Note that in the product, the new C-C bond is made to the carbon <em><strong>neighboring<\/strong><\/em> the alcohol carbon.\u00a0 (In contrast, when organometallics add to carbonyls, the new C-C bond ends up directly bonded to the alcohol carbon.)\r\n<h3 id=\"title\">Reaction of nitriles (RCN) with Grignard reagents: Synthesis of ketones<\/h3>\r\n<dl class=\"mt-last-updated-container\"><\/dl>\r\n<\/header><section class=\"mt-content-container\"><a title=\"Grignard Reagents\" href=\"https:\/\/chem.libretexts.org\/?title=Textbook_Maps\/Organic_Chemistry\/Supplemental_Modules_(Organic_Chemistry)\/Aldehydes_and_Ketones\/Synthesis_of_Aldehydes_%26_Ketones\/Grignard_Reagents\" rel=\"internal\">Grignard reagents<\/a> can attack the electophilic carbon in a nitrile to form an imine salt.\u00a0This salt can then be hydrolyzed to become a ketone.\r\n<div id=\"section_1\" class=\"mt-section\">\r\n<h4 class=\"editable\">General reaction<\/h4>\r\n<img class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170933\/1.jpg\" alt=\"1.jpg\" \/>\r\n\r\n<\/div>\r\n<div id=\"section_2\" class=\"mt-section\">\r\n<div class=\"textbox examples\">\r\n<h3>Example<\/h3>\r\n<div id=\"section_2\" class=\"mt-section\">\r\n\r\n<img class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170935\/2.jpg\" alt=\"2.jpg\" \/>\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<div id=\"section_3\" class=\"mt-section\">\r\n<h3 class=\"editable\">Mechanism<\/h3>\r\n1) Nucleophilic attack by the Grignard reagent\r\n\r\n<img class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170939\/3.jpg\" alt=\"3.jpg\" \/>\r\n\r\n2) Protonation\r\n\r\n<img class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170941\/4.jpg\" alt=\"4.jpg\" \/>\r\n\r\n3) Protonation\r\n\r\n<img class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170943\/5.jpg\" alt=\"5.jpg\" \/>\r\n\r\n4) Nucleophilic attack by water\r\n\r\n<img class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170945\/6.jpg\" alt=\"6.jpg\" \/>\r\n\r\n5) Proton Transfer\r\n\r\n<img class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170947\/7.jpg\" alt=\"7.jpg\" \/>\r\n\r\n6)\u00a0 Leaving group removal\r\n\r\n<img class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170949\/8.jpg\" alt=\"8.jpg\" \/>\r\n\r\n7) Deprotonation\r\n\r\n<img class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170952\/9.jpg\" alt=\"9.jpg\" \/>\r\n\r\n<\/div>\r\n<h4 class=\"editable\">Contributors<\/h4>\r\nProf. Steven Farmer (<a class=\"external\" title=\"http:\/\/www.sonoma.edu\" href=\"http:\/\/www.sonoma.edu\" target=\"_blank\" rel=\"external nofollow noopener\">Sonoma State University<\/a>)\r\n<h2 id=\"section_4\" class=\"mt-section\">20.3.3. Terminal alkynes as carbon nucleophiles<\/h2>\r\n<div class=\"mt-section\"><section class=\"mt-content-container\">\r\n<div id=\"section_18\">\r\n<div id=\"section_3\" class=\"mt-section\">\r\n\r\nRecall from <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-8-substitution-with-acetylides\/\">section 9.8<\/a> that the hydrogen on a terminal alkyne is somewhat acidic, with a pK<sub>a<\/sub> of approximately 25.\u00a0 This means that, given a strong enough base, terminal alkyne can be deprotonated, yielding a powerful carbanion nucleophile, which we used in S<sub>N<\/sub>2 reactions.\u00a0 Sodium hydride, or sodium amide in liquid ammonia is often used for this purpose.\r\n\r\n<img class=\"\u201cinternal internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28171222\/image133.png\" alt=\"image134.png\" width=\"652px\" height=\"173px\" \/>\r\n\r\nThe alkynyl carbanion can then be combined with a suitable electrophile, such as a primary alkyl bromide, in a carbon-carbon bond-forming\u00a0 S<sub>N<\/sub>2 displacement reaction.\u00a0 However it can also add to polar bonds in the same way as a Grignard reagent, for example giving an alcohol when added to a ketone.\r\n\r\n<\/div>\r\n<\/div>\r\n<div id=\"section_19\">\r\n<div id=\"section_4\" class=\"mt-section\">\r\n\r\nGrignard reagents will not react efficiently in S<sub>N<\/sub>2 reactions with alkyl halides (the Gilman reagent, described below, can be used for this purpose).\r\n<div>\r\n<div class=\"mt-section\">\r\n<h3 class=\"editable\">Contributors<\/h3>\r\n<ul>\r\n \t<li><a title=\"http:\/\/chemwiki.ucdavis.edu\/Organic_Chemistry\/Organic_Chemistry_With_a_Biological_Emphasis\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Book%3A_Organic_Chemistry_with_a_Biological_Emphasis_(Soderberg)\" rel=\"internal\"><strong>Organic Chemistry With a Biological Emphasis <\/strong><\/a>by\u00a0<a class=\"external\" title=\"http:\/\/facultypages.morris.umn.edu\/~soderbt\/\" href=\"http:\/\/facultypages.morris.umn.edu\/%7Esoderbt\/\" target=\"_blank\" rel=\"external nofollow noopener\">Tim Soderberg<\/a>\u00a0(University of Minnesota, Morris)<\/li>\r\n<\/ul>\r\n<header><header><header><header>\r\n<h2 class=\"editable\">20.3.4. Reactions of organocuprates (Gilman Reagents)<\/h2>\r\n<\/header><section class=\"mt-content-container\">\r\n<div id=\"skills\">\r\n<div class=\"textbox learning-objectives\">\r\n<h3>Learning Objectives<\/h3>\r\n<div id=\"skills\">\r\n\r\nAfter completing this section, you should be able to\r\n<ol>\r\n \t<li>write an equation for the formation of an alkyllithium from an alkyl halide.<\/li>\r\n \t<li>write an equation for the formation of a lithium dialkylcopper (Gilman) reagent from an alkyllithium and copper(I) iodide.<\/li>\r\n \t<li>write an equation for the coupling of a lithium dialkylcopper reagent with an alkyl halide (i.e., a Corey-House synthesis).<\/li>\r\n \t<li>draw the structure of the product formed from a given Corey-House synthesis.<\/li>\r\n \t<li>identify the reagents needed to convert two given organohalides to a specified hydrocarbon through a Corey-House synthesis.<\/li>\r\n<\/ol>\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<div id=\"section_2\" class=\"mt-section\">\r\n<h3 class=\"editable\">Preparation of Gilman reagents<\/h3>\r\nThe Gilman reagent is a lithium diorganocopper species that can be prepared from organolithium compounds:\r\n\r\n<img class=\"\u201cinternal internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28171249\/image151.png\" alt=\"image152.png\" width=\"464px\" height=\"37px\" \/>\r\n<h3>Coupling reactions of Gilman reagents with alkyl and acyl halides<\/h3>\r\nGilman reagents are useful in that, unlike Grignard reagents, they will efficiently react in S<sub>N<\/sub>2 reactions with alkyl halides, even when the halogen is bonded to an sp<sup>2<\/sup>-hybridized, alkene carbon (remember from <a title=\"Organic Chemistry\/Organic Chemistry With a Biological Emphasis\/Chapter 8: Nucleophilic substitution reactions I\/Section 2: Two mechanistic models for a nucleophilic substitution reaction\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Book%3A_Organic_Chemistry_with_a_Biological_Emphasis_(Soderberg)\/Chapter_08%3A_Nucleophilic_substitution_reactions_I\/8.2%3A_Two_mechanistic_models_for_a_nucleophilic_substitution_reaction\" rel=\"internal\">section 8.2C <\/a>that S<sub>N<\/sub>2 reactions typically do not occur at sp<sup>2<\/sup>-hybridized carbons!)\r\n\r\n<img class=\"\u201cinternal internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28171252\/image153.png\" alt=\"image154.png\" width=\"746px\" height=\"166px\" \/>\r\n\r\nIn general, we see:\r\n\r\n<\/div>\r\n<div><img class=\"size-full wp-image-2559 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/12203111\/download-22.png\" alt=\"\" width=\"624\" height=\"96\" \/><\/div>\r\n<div id=\"section_3\" class=\"mt-section\">\r\n<div class=\"textbox examples\">\r\n<h3>Examples<\/h3>\r\n<img class=\"size-full wp-image-2560 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/12203139\/download-3.png\" alt=\"\" width=\"568\" height=\"101\" \/>\r\n\r\n<img class=\"size-full wp-image-2562 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/12203214\/download-4.png\" alt=\"\" width=\"624\" height=\"138\" \/>\r\n\r\n<img class=\"size-full wp-image-2561 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/12203211\/download-5.png\" alt=\"\" width=\"624\" height=\"152\" \/>\r\n\r\n&nbsp;\r\n\r\n<\/div>\r\n<\/div>\r\n<div id=\"section_4\" class=\"mt-section\">\r\n<div class=\"textbox exercises\">\r\n<h3>Exercises<\/h3>\r\n<ol>\r\n \t<li>Starting with alkyl halides containing no more than four carbon atoms, how would you synthesize each of the following alkanes?\r\n<ol>\r\n \t<li>2,5-dimethylhexane<\/li>\r\n \t<li>2-methylhexane<\/li>\r\n<\/ol>\r\n<\/li>\r\n<\/ol>\r\n<div id=\"section_5\" class=\"mt-section\">\r\n<h3 class=\"editable\">Answers<\/h3>\r\n<ol>\r\n \t<li><img class=\"size-full wp-image-2564 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/12203454\/10-7a-answer.png\" alt=\"\" width=\"521\" height=\"267\" \/><\/li>\r\n \t<li><img class=\" wp-image-2563 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/12203451\/10-7b-answer.png\" alt=\"\" width=\"470\" height=\"211\" \/><\/li>\r\n<\/ol>\r\n&nbsp;\r\n\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<\/section><\/header><\/header><section class=\"mt-content-container\">\r\n<div id=\"section_1\" class=\"mt-section\">\r\n<h3>Conjugate addition of Gilman reagents<\/h3>\r\nAnother useful reaction of organocuprates is the so-called \"conjugate addition\" to C=C-C=O compounds, often called .\u00a0 Whereas RMgX and RLi will simply add normally to the C=O of such compounds, the R<sub>2<\/sub>CuLi will add to the alkene portion rather than directly to the carbonyl:\r\n\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170544\/15.jpg\" alt=\"15.jpg\" width=\"320px\" height=\"128px\" \/>\r\n<div class=\"textbox examples\">\r\n<h3>Examples<\/h3>\r\n<img class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170546\/16.jpg\" alt=\"16.jpg\" width=\"403px\" height=\"111px\" \/>\r\n\r\n<\/div>\r\n<\/div>\r\n<\/section><\/header><section class=\"mt-content-container\"><header><section class=\"mt-content-container\">\r\n<div id=\"section_6\" class=\"mt-section\">\r\n<h3 class=\"editable\">Contributors<\/h3>\r\n<ul>\r\n \t<li><a class=\"external\" title=\"http:\/\/science.athabascau.ca\/staff-pages\/dietmark\" href=\"http:\/\/science.athabascau.ca\/staff-pages\/dietmark\" target=\"_blank\" rel=\"external nofollow noopener\">Dr. Dietmar Kennepohl<\/a> FCIC (Professor of Chemistry, <a class=\"external\" title=\"http:\/\/www.athabascau.ca\/\" href=\"http:\/\/www.athabascau.ca\/\" target=\"_blank\" rel=\"external nofollow noopener\">Athabasca University<\/a>)<\/li>\r\n \t<li>Prof. Steven Farmer (<a class=\"external\" title=\"http:\/\/www.sonoma.edu\" href=\"http:\/\/www.sonoma.edu\" target=\"_blank\" rel=\"external nofollow noopener\">Sonoma State University<\/a>)<\/li>\r\n<\/ul>\r\n<h3>Video<\/h3>\r\nhttps:\/\/youtu.be\/a-ksnhFbTRs\r\n\r\n<img class=\"alignnone size-thumbnail wp-image-3007\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/08152957\/frame-38-150x150.png\" alt=\"\" width=\"150\" height=\"150\" \/>\r\n\r\n<header><\/header><\/div>\r\n<\/section><\/header><\/section><\/div>\r\n<\/div>\r\n<\/div>\r\n<\/div>\r\n<\/section><\/div>\r\n<\/section><\/div>\r\n<\/section><\/div>\r\n<\/section><\/div>","rendered":"<article id=\"elm-main-content\" class=\"elm-content-container\">\n<h2 class=\"mt-content-container\">20.3.1. A digression: Formation and properties of organometallic reagents<\/h2>\n<p>The <a title=\"Group 1: The Alkali Metals\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Inorganic_Chemistry\/Supplemental_Modules_(Inorganic_Chemistry)\/Descriptive_Chemistry\/Elements_Organized_by_Block\/1_s-Block_Elements\/Group__1%3A_The_Alkali_Metals\" rel=\"internal\">alkali metals<\/a> (Li, Na, K etc.) and the <a title=\"Group 2 Elements: The Alkaline Earth Metals\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Inorganic_Chemistry\/Supplemental_Modules_(Inorganic_Chemistry)\/Descriptive_Chemistry\/Elements_Organized_by_Block\/1_s-Block_Elements\/Group__2_Elements%3A_The_Alkaline_Earth_Metals\" rel=\"internal\">alkaline earth metals<\/a> (Mg and Ca, together with Zn) are good reducing agents, the former being stronger than the latter. These same metals reduce the carbon-halogen bonds of alkyl halides. The halogen is converted to a halide anion, and the carbon bonds to the metal which has characteristics similar to a <a title=\"Carbanions\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Supplemental_Modules_(Organic_Chemistry)\/Fundamentals\/Reactive_Intermediates\/Carbanions\" rel=\"internal\">carbanion <\/a>(R:-).<\/p>\n<div id=\"section_1\" class=\"mt-section\">\n<h3 class=\"editable\">Formation of organometallic reagents<\/h3>\n<p>Many organometallic reagents are commercially available, however, it is often necessary to make then. The following equations illustrate these reactions for the commonly used metals lithium and magnesium (R may be hydrogen or alkyl groups in any combination).<\/p>\n<ul>\n<li>\n<h3>An alkyllithium reagent<\/h3>\n<\/li>\n<\/ul>\n<p style=\"text-align: center\"><span id=\"MathJax-Span-9\" class=\"msubsup\"><span id=\"MathJax-Span-10\" class=\"mtext\">R<sub>3<\/sub><\/span><span id=\"MathJax-Span-11\" class=\"texatom\"><span id=\"MathJax-Span-12\" class=\"mrow\"><span id=\"MathJax-Span-13\" class=\"mspace\"><\/span><\/span><\/span><\/span><span id=\"MathJax-Span-17\" class=\"mtext\">C<\/span><span id=\"MathJax-Span-18\" class=\"texatom\"><span id=\"MathJax-Span-19\" class=\"mrow\"><span id=\"MathJax-Span-20\" class=\"mo\">\u2212<\/span><\/span><\/span><span id=\"MathJax-Span-21\" class=\"mtext\">X<\/span><span id=\"MathJax-Span-22\" class=\"mo\">+<\/span><span id=\"MathJax-Span-23\" class=\"mn\">2<\/span><span id=\"MathJax-Span-24\" class=\"mspace\"><\/span><span id=\"MathJax-Span-25\" class=\"mtext\">Li<\/span><span id=\"MathJax-Span-26\" class=\"mo\">\u2192<\/span><span id=\"MathJax-Span-27\" class=\"msubsup\"><span id=\"MathJax-Span-28\" class=\"mtext\">R<\/span><span id=\"MathJax-Span-29\" class=\"texatom\"><span id=\"MathJax-Span-30\" class=\"mrow\"><span id=\"MathJax-Span-31\" class=\"mspace\"><\/span><\/span><\/span><sub><span id=\"MathJax-Span-32\" class=\"texatom\"><span id=\"MathJax-Span-33\" class=\"mrow\"><span id=\"MathJax-Span-34\" class=\"mn\">3<\/span><\/span><\/span><\/sub><\/span><span id=\"MathJax-Span-35\" class=\"mtext\">C<\/span><span id=\"MathJax-Span-36\" class=\"texatom\"><span id=\"MathJax-Span-37\" class=\"mrow\"><span id=\"MathJax-Span-38\" class=\"mo\">\u2212<\/span><\/span><\/span><span id=\"MathJax-Span-39\" class=\"mtext\">Li<\/span><span id=\"MathJax-Span-40\" class=\"mo\">+<\/span><span id=\"MathJax-Span-41\" class=\"mtext\">LiX<\/span><\/p>\n<ul>\n<li>\n<h3>A Grignard reagent<\/h3>\n<\/li>\n<\/ul>\n<p style=\"text-align: center\"><span id=\"MathJax-Span-50\" class=\"msubsup\"><span id=\"MathJax-Span-51\" class=\"mtext\">R<\/span><span id=\"MathJax-Span-52\" class=\"texatom\"><span id=\"MathJax-Span-53\" class=\"mrow\"><span id=\"MathJax-Span-54\" class=\"mspace\"><\/span><\/span><\/span><sub><span id=\"MathJax-Span-55\" class=\"texatom\"><span id=\"MathJax-Span-56\" class=\"mrow\"><span id=\"MathJax-Span-57\" class=\"mn\">3<\/span><\/span><\/span><\/sub><\/span><span id=\"MathJax-Span-58\" class=\"mtext\">C<\/span><span id=\"MathJax-Span-59\" class=\"texatom\"><span id=\"MathJax-Span-60\" class=\"mrow\"><span id=\"MathJax-Span-61\" class=\"mo\">\u2212<\/span><\/span><\/span><span id=\"MathJax-Span-62\" class=\"mtext\">X<\/span><span id=\"MathJax-Span-63\" class=\"mo\">+<\/span><span id=\"MathJax-Span-64\" class=\"mtext\">Mg<\/span><span id=\"MathJax-Span-65\" class=\"mo\">\u2192<\/span><span id=\"MathJax-Span-66\" class=\"msubsup\"><span id=\"MathJax-Span-67\" class=\"mtext\">R<\/span><span id=\"MathJax-Span-68\" class=\"texatom\"><span id=\"MathJax-Span-69\" class=\"mrow\"><span id=\"MathJax-Span-70\" class=\"mspace\"><\/span><\/span><\/span><sub><span id=\"MathJax-Span-71\" class=\"texatom\"><span id=\"MathJax-Span-72\" class=\"mrow\"><span id=\"MathJax-Span-73\" class=\"mn\">3<\/span><\/span><\/span><\/sub><\/span><span id=\"MathJax-Span-74\" class=\"mtext\">C<\/span><span id=\"MathJax-Span-75\" class=\"texatom\"><span id=\"MathJax-Span-76\" class=\"mrow\"><span id=\"MathJax-Span-77\" class=\"mo\">\u2212<\/span><\/span><\/span><span id=\"MathJax-Span-78\" class=\"mtext\">MgX<\/span><\/p>\n<p>Halide reactivity in these reactions increases in the order: Cl &lt; Br &lt; I and fluorides are usually not used. The alkyl magnesium halides described in the second reaction are called Grignard reagents after the French chemist, Victor Grignard, who discovered them and received the Nobel prize in 1912 for this work. The other metals mentioned above react in a similar manner, but Grignard and Alkyllithium reagents are the most widely used. Although the formulae drawn here for the alkyllithium and Grignard reagents reflect the stoichiometry of the reactions and are widely used in the chemical literature, they do not accurately depict the structural nature of these remarkable substances. Mixtures of polymeric and other associated and complexed species are in equilibrium under the conditions normally used for their preparation.<\/p>\n<p>A suitable solvent must be used. For alkyllithium formation pentane or hexane is usually used. Diethyl ether can also be used but the subsequent alkyllithium reagent must be used immediately after preparation due to an interaction with the solvent. Ethyl ether or THF are essential for Grignard reagent formation. Lone pair electrons from two ether molecules form a complex with the magnesium in the Grignard reagent (As pictured below). This complex helps stabilize the organometallic and increases its ability to react.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170011\/3.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image006.png\" width=\"198\" height=\"189\" \/><\/p>\n<p>These reactions are obviously substitution reactions, but they cannot be classified as nucleophilic substitutions, as were the earlier reactions of alkyl halides. Because the functional carbon atom has been reduced, the polarity of the resulting functional group is inverted (an originally electrophilic carbon becomes nucleophilic). This change, shown below, makes alkyl lithium and Grignard reagents excellent nucleophiles and useful reactants in synthesis.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170013\/4.jpg\" alt=\"http:\/\/www2.chemistry.msu.edu\/faculty\/reusch\/VirtTxtJml\/Images2\/fncpolar.gif\" width=\"321\" height=\"211\" \/><\/p>\n<div>\n<div id=\"example\">\n<div class=\"textbox examples\">\n<h3>Examples<\/h3>\n<div id=\"section_1\" class=\"mt-section\">\n<div id=\"example\">\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170016\/5.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image010.png\" width=\"418\" height=\"91\" \/><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170018\/6.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image012.png\" width=\"360\" height=\"95\" \/><\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"section_2\" class=\"mt-section\">\n<h3 class=\"editable\">Common organometallic reagents<\/h3>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170020\/7.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image014.png\" width=\"489\" height=\"115\" \/><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170023\/8.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image016.png\" width=\"380\" height=\"109\" \/><\/p>\n<div id=\"section_5\" class=\"mt-section\">\n<h3 class=\"editable\">Organometallic reagents as bases<\/h3>\n<p>These reagents are very strong bases (pKa&#8217;s of saturated hydrocarbons range are around 50). Although not usually done with Grignard reagents, organolithium reagents can be used as strong bases. Both Grignard reagents and organolithium reagents react with water to form the corresponding hydrocarbon. This is why so much care is needed to insure dry glassware and solvents when working with organometallic reagents.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170048\/18.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image036.png\" width=\"551\" height=\"89\" \/><\/p>\n<p>In fact, the reaction of Grignard reagents and organolithium reagents with water can be exploited to convert alkyl halides into the corresponding hydrocarbon (illustrated below). The halogen is converted to an organometallic reagent and then subsequently reacted with water to form an alkane.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170050\/19.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image038.png\" width=\"319\" height=\"94\" \/><\/p>\n<\/div>\n<div id=\"section_6\" class=\"mt-section\">\n<h3 class=\"editable\">Limitation of organometallic reagents<\/h3>\n<p>As discussed above, Grignard and organolithium reagents are powerful bases. Because of this they cannot be used as nucleophiles on compounds which contain acidic hydrogens.\u00a0 If they are used they will act as a base and deprotonate the acidic hydrogen rather than act as a nucleophile and attack the carbonyl.\u00a0 A partial list of functional groups which cannot be used are: alcohols, amides, 1<sup>o<\/sup> amines (RNH<sub>2<\/sub>), 2<sup>o<\/sup> amines (R<sub>2<\/sub>NH), carboxylic acids, and terminal alkynes.<\/p>\n<p><img decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170052\/20.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image040.png\" \/><\/p>\n<h3>Video<\/h3>\n<p><iframe loading=\"lazy\" id=\"oembed-1\" title=\"Introduction to Organometallic Compounds\" width=\"500\" height=\"281\" src=\"https:\/\/www.youtube.com\/embed\/3FRV31YYtL8?feature=oembed&#38;rel=0\" frameborder=\"0\" allowfullscreen=\"allowfullscreen\"><\/iframe><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-thumbnail wp-image-3006\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/08152802\/frame-37-150x150.png\" alt=\"\" width=\"150\" height=\"150\" \/><\/p>\n<\/div>\n<\/div>\n<div id=\"section_3\" class=\"mt-section\">\n<h2 class=\"editable\">20.3.2. Reaction of organometallic reagents with polar bonds<\/h2>\n<p>Both &#8216;Grignard reagents&#8217; and organolithiums are particularly useful in nucleophilic addition reactions with carbonyl electrophiles, such as ketones:<\/p>\n<p><img decoding=\"async\" class=\"\u201cinternal internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28171232\/image139.png\" alt=\"image140.png\" width=\"755px\" height=\"95px\" \/><\/p>\n<p>The nucleophilic carbon need not be primary as in the picture above.\u00a0 The synthesis of 2-phenyl-2-propanol,\u00a0 for example, can be carried by reacting phenylmagnesium bromide with acetone.<\/p>\n<p><img decoding=\"async\" class=\"\u201cinternal internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28171236\/image141.png\" alt=\"image142.png\" width=\"676px\" height=\"111px\" \/><\/p>\n<p>Addition to formaldehyde gives 1<sup>o<\/sup> alcohols<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170027\/10.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image020.png\" width=\"343\" height=\"117\" \/><\/p>\n<p>Addition to aldehydes gives 2<sup>o<\/sup> alcohols<br \/>\n<img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170030\/11.jpg\" alt=\"11.jpg\" width=\"340\" height=\"117\" \/><\/p>\n<p>Addition to ketones gives 3<sup>o<\/sup> alcohols<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170032\/12.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image024.png\" width=\"327\" height=\"114\" \/><\/p>\n<h3>Reaction of organometallic reagents with carbon dioxide: Synthesis of carboxylic acids<\/h3>\n<p>Grignard reagents can be also be carboxylated simply by pouring the organic solution over dry ice (solid CO<sub>2<\/sub>), then adding aqueous HCl:<\/p>\n<p><img decoding=\"async\" class=\"\u201cinternal internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28171239\/image143.png\" alt=\"image144.png\" width=\"379px\" height=\"105px\" \/><\/p>\n<p>Or in general:<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170034\/13.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image026.png\" width=\"355\" height=\"125\" \/><\/p>\n<div>\n<div class=\"textbox examples\">\n<h3>Examples<\/h3>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170037\/14.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image028.png\" width=\"519\" height=\"677\" \/><\/p>\n<\/div>\n<\/div>\n<p>Going from reactants to products simplified<\/p>\n<p><img decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170039\/15.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image030.png\" \/><\/p>\n<\/div>\n<div id=\"section_4\" class=\"mt-section\">\n<h3 class=\"editable\">Mechanism for the addition to carbonyls<\/h3>\n<p>The mechanism for a Grignard agent is shown.\u00a0 The mechanism for an organolithium reagent is essentially the same.<\/p>\n<p>1)\u00a0 Nucleophilic attack<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170043\/16.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image032.png\" width=\"291\" height=\"126\" \/><\/p>\n<p>2) Protonation<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170045\/17.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image034.png\" width=\"489\" height=\"130\" \/><\/p>\n<\/div>\n<div id=\"section_7\" class=\"mt-section\">\n<div class=\"textbox examples\">\n<div id=\"section_7\" class=\"mt-section\">\n<h3 class=\"editable\">Problems<\/h3>\n<p>1) Please write the product of the following reactions.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170055\/21.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image042.png\" width=\"484\" height=\"525\" \/><\/p>\n<p>2) Please indicate the starting material required to produce the product.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170057\/22.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image044.png\" width=\"472\" height=\"462\" \/><\/p>\n<p>3) Please give a detailed mechanism and the final product of this reaction<\/p>\n<p><img decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170100\/23.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image046.png\" \/><\/p>\n<p>4)\u00a0 Please show two sets of reactants which could be used to synthesize the following molecule using a Grignard reaction.<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170102\/24.jpg\" alt=\"File:\/C:\\Users\\Joy\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image048.png\" width=\"163\" height=\"102\" \/><\/p>\n<p>&nbsp;<\/p>\n<\/div>\n<div id=\"section_8\" class=\"mt-section\">\n<h3 class=\"editable\">Answers<\/h3>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q336398\">Show Answer<\/span><\/p>\n<div id=\"q&#8221;336398&#8243;\" class=\"hidden-answer\" style=\"display: none\">\n<\/div>\n<\/div>\n<\/div>\n<div id=\"section_9\" class=\"mt-section\">\n<h4 class=\"editable\">Contributors<\/h4>\n<ul>\n<li><a class=\"external\" title=\"http:\/\/science.athabascau.ca\/staff-pages\/dietmark\" href=\"http:\/\/science.athabascau.ca\/staff-pages\/dietmark\" target=\"_blank\" rel=\"external nofollow noopener\">Dr. Dietmar Kennepohl<\/a> FCIC (Professor of Chemistry, <a class=\"external\" title=\"http:\/\/www.athabascau.ca\/\" href=\"http:\/\/www.athabascau.ca\/\" target=\"_blank\" rel=\"external nofollow noopener\">Athabasca University<\/a>)<\/li>\n<li>Prof. Steven Farmer (<a class=\"external\" title=\"http:\/\/www.sonoma.edu\" href=\"http:\/\/www.sonoma.edu\" target=\"_blank\" rel=\"external nofollow noopener\">Sonoma State University<\/a>)<\/li>\n<\/ul>\n<header><\/header>\n<\/div>\n<\/article>\n<div id=\"section_9\" class=\"mt-section\">\n<header><\/header>\n<section class=\"mt-content-container\">\n<div id=\"section_6\" class=\"mt-section\">\n<section class=\"mt-content-container\">\n<h3 id=\"note\">Reaction with esters<\/h3>\n<div id=\"section_1\" class=\"mt-section\">\n<p>Esters and acid chlorides will react with <em>two<\/em> molar equivalents of Grignard reagent:<\/p>\n<p><img decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28171244\/image148.png\" alt=\"image148.png\" width=\"578px\" height=\"350px\" \/><\/p>\n<p>The first reaction is an acyl substitution reaction, and the second is a nucleophilic carbonyl addition. Because ketones and aldehydes are better electrophiles than carboxylic acid derivatives, it is not possible to stop these reactions at the ketone\/aldehyde stage.<\/p>\n<p>In general, we see the attachment of <strong>two identical R&#8217; groups<\/strong> from the organometallic in the alcohol product:<\/p>\n<p><img decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170719\/1.jpg\" alt=\"File:\/C:\\Users\\Gantor\\AppData\\Local\\Temp\\msohtmlclip1\\01\\clip_image002.png\" \/><\/p>\n<p>Carboxylic acids and amides will simply protonate the Grignard reagent, not a terribly productive reaction.<\/p>\n<\/div>\n<div id=\"section_2\" class=\"mt-section\">\n<div>\n<div class=\"textbox examples\">\n<h3>Examples<\/h3>\n<p><img decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170721\/2.jpg\" alt=\"2.jpg\" \/><\/p>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"section_4\" class=\"mt-section\">\n<div class=\"textbox exercises\">\n<h3>Exercises<\/h3>\n<div id=\"section_4\" class=\"mt-section\">\n<div id=\"s61700\" class=\"mt-include\">\n<div id=\"section_15\" class=\"mt-section\">\n<p><strong>1.<\/strong><\/p>\n<p>If allylmagnesium\u00a0chloride (CH<sub>2<\/sub>=CH=CH<sub>2<\/sub>MgCl) were added to a solution of the following compound and then worked-up with acid, the product would contain a chiral center.\u00a0Would the product be a racemic mixture (optically inactive) or an enantiomerically pure product (optically active)? Draw both enantiomers.<\/p>\n<p><img decoding=\"async\" class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170725\/17.24q.png\" alt=\"\" width=\"144px\" height=\"138px\" \/><\/p>\n<p><strong>2.<\/strong><\/p>\n<p>What combination of carbonyl compound and Grignard\u00a0(use MgBr)\u00a0reagent would yield the following alcohols (after workup)?<\/p>\n<p>(a)\u00a0<img loading=\"lazy\" decoding=\"async\" class=\"internal\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170726\/17.30aq.png\" alt=\"\" width=\"100\" height=\"116\" \/>\u00a0\u00a0 \u00a0 (b)\u00a0<img loading=\"lazy\" decoding=\"async\" class=\"internal\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170727\/17.30bq.png\" alt=\"\" width=\"141\" height=\"63\" \/>\u00a0\u00a0 \u00a0 (c)\u00a0<img loading=\"lazy\" decoding=\"async\" class=\"internal\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170729\/17.30cq.png\" alt=\"\" width=\"114\" height=\"94\" \/>\u00a0\u00a0 \u00a0 (d)\u00a0<img loading=\"lazy\" decoding=\"async\" class=\"internal\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170730\/17.30dq.png\" alt=\"\" width=\"139\" height=\"98\" \/><\/p>\n<p>&nbsp;<\/p>\n<\/div>\n<div id=\"section_16\" class=\"mt-section\">\n<h3 id=\"Solutions-61700\">Solutions<\/h3>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q317037\">Show Answer<\/span><\/p>\n<div id=\"q317037\" class=\"hidden-answer\" style=\"display: none\"><\/div>\n<\/div>\n<p><strong>1.<\/strong><\/p>\n<p>The result would be a racemic mixture of the following.<\/p>\n<p><img decoding=\"async\" class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170736\/17.24a.png\" alt=\"\" width=\"343px\" height=\"150px\" \/><\/p>\n<p><strong>2.<\/strong><\/p>\n<p>(a)\u00a0<img loading=\"lazy\" decoding=\"async\" class=\"internal\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170738\/17.30aa.png\" alt=\"\" width=\"314\" height=\"71\" \/>\u00a0\u00a0 \u00a0 (b)\u00a0\u00a0<img loading=\"lazy\" decoding=\"async\" class=\"internal\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170740\/17.30ba..png\" alt=\"\" width=\"252\" height=\"72\" \/>\u00a0 \u00a0 (c)\u00a0<img loading=\"lazy\" decoding=\"async\" class=\"internal\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170743\/17.30ca.png\" alt=\"\" width=\"225\" height=\"70\" \/><\/p>\n<p>(d)\u00a0<img loading=\"lazy\" decoding=\"async\" class=\"internal\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170745\/17.30da.png\" alt=\"\" width=\"248\" height=\"77\" \/><\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<h4 class=\"editable\">Contributors<\/h4>\n<\/div>\n<div id=\"section_5\" class=\"mt-section\">\n<ul>\n<li><a class=\"external\" title=\"http:\/\/science.athabascau.ca\/staff-pages\/dietmark\" href=\"http:\/\/science.athabascau.ca\/staff-pages\/dietmark\" target=\"_blank\" rel=\"external nofollow noopener\">Dr. Dietmar Kennepohl<\/a> FCIC (Professor of Chemistry, <a class=\"external\" title=\"http:\/\/www.athabascau.ca\/\" href=\"http:\/\/www.athabascau.ca\/\" target=\"_blank\" rel=\"external nofollow noopener\">Athabasca University<\/a>)<\/li>\n<li>Prof. Steven Farmer (<a class=\"external\" title=\"http:\/\/www.sonoma.edu\" href=\"http:\/\/www.sonoma.edu\" target=\"_blank\" rel=\"external nofollow noopener\">Sonoma State University<\/a>)<\/li>\n<\/ul>\n<header>\n<h3>Reaction of organometallics with epoxides<\/h3>\n<p>Grignard and organolithium reagents will also react with epoxides, attacking the less hindered carbon (as expected for basic\/nucleophilic ring-opening conditions \u2013 see <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-6-epoxide-reactions\/\">section 9.6<\/a>).<\/p>\n<p><img decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28171241\/image145.png\" alt=\"image145.png\" width=\"463px\" height=\"122px\" \/><\/p>\n<p>Being a strong nucleophile, the organometallic attacks the epoxide from the less hindered end of the epoxide ring.\u00a0 Note that in the product, the new C-C bond is made to the carbon <em><strong>neighboring<\/strong><\/em> the alcohol carbon.\u00a0 (In contrast, when organometallics add to carbonyls, the new C-C bond ends up directly bonded to the alcohol carbon.)<\/p>\n<h3 id=\"title\">Reaction of nitriles (RCN) with Grignard reagents: Synthesis of ketones<\/h3>\n<dl class=\"mt-last-updated-container\"><\/dl>\n<\/header>\n<section class=\"mt-content-container\"><a title=\"Grignard Reagents\" href=\"https:\/\/chem.libretexts.org\/?title=Textbook_Maps\/Organic_Chemistry\/Supplemental_Modules_(Organic_Chemistry)\/Aldehydes_and_Ketones\/Synthesis_of_Aldehydes_%26_Ketones\/Grignard_Reagents\" rel=\"internal\">Grignard reagents<\/a> can attack the electophilic carbon in a nitrile to form an imine salt.\u00a0This salt can then be hydrolyzed to become a ketone.<\/p>\n<div id=\"section_1\" class=\"mt-section\">\n<h4 class=\"editable\">General reaction<\/h4>\n<p><img decoding=\"async\" class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170933\/1.jpg\" alt=\"1.jpg\" \/><\/p>\n<\/div>\n<div id=\"section_2\" class=\"mt-section\">\n<div class=\"textbox examples\">\n<h3>Example<\/h3>\n<div id=\"section_2\" class=\"mt-section\">\n<p><img decoding=\"async\" class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170935\/2.jpg\" alt=\"2.jpg\" \/><\/p>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"section_3\" class=\"mt-section\">\n<h3 class=\"editable\">Mechanism<\/h3>\n<p>1) Nucleophilic attack by the Grignard reagent<\/p>\n<p><img decoding=\"async\" class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170939\/3.jpg\" alt=\"3.jpg\" \/><\/p>\n<p>2) Protonation<\/p>\n<p><img decoding=\"async\" class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170941\/4.jpg\" alt=\"4.jpg\" \/><\/p>\n<p>3) Protonation<\/p>\n<p><img decoding=\"async\" class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170943\/5.jpg\" alt=\"5.jpg\" \/><\/p>\n<p>4) Nucleophilic attack by water<\/p>\n<p><img decoding=\"async\" class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170945\/6.jpg\" alt=\"6.jpg\" \/><\/p>\n<p>5) Proton Transfer<\/p>\n<p><img decoding=\"async\" class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170947\/7.jpg\" alt=\"7.jpg\" \/><\/p>\n<p>6)\u00a0 Leaving group removal<\/p>\n<p><img decoding=\"async\" class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170949\/8.jpg\" alt=\"8.jpg\" \/><\/p>\n<p>7) Deprotonation<\/p>\n<p><img decoding=\"async\" class=\"internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170952\/9.jpg\" alt=\"9.jpg\" \/><\/p>\n<\/div>\n<h4 class=\"editable\">Contributors<\/h4>\n<p>Prof. Steven Farmer (<a class=\"external\" title=\"http:\/\/www.sonoma.edu\" href=\"http:\/\/www.sonoma.edu\" target=\"_blank\" rel=\"external nofollow noopener\">Sonoma State University<\/a>)<\/p>\n<h2 id=\"section_4\" class=\"mt-section\">20.3.3. Terminal alkynes as carbon nucleophiles<\/h2>\n<div class=\"mt-section\">\n<section class=\"mt-content-container\">\n<div id=\"section_18\">\n<div id=\"section_3\" class=\"mt-section\">\n<p>Recall from <a href=\"https:\/\/courses.lumenlearning.com\/suny-potsdam-organicchemistry\/chapter\/9-8-substitution-with-acetylides\/\">section 9.8<\/a> that the hydrogen on a terminal alkyne is somewhat acidic, with a pK<sub>a<\/sub> of approximately 25.\u00a0 This means that, given a strong enough base, terminal alkyne can be deprotonated, yielding a powerful carbanion nucleophile, which we used in S<sub>N<\/sub>2 reactions.\u00a0 Sodium hydride, or sodium amide in liquid ammonia is often used for this purpose.<\/p>\n<p><img decoding=\"async\" class=\"\u201cinternal internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28171222\/image133.png\" alt=\"image134.png\" width=\"652px\" height=\"173px\" \/><\/p>\n<p>The alkynyl carbanion can then be combined with a suitable electrophile, such as a primary alkyl bromide, in a carbon-carbon bond-forming\u00a0 S<sub>N<\/sub>2 displacement reaction.\u00a0 However it can also add to polar bonds in the same way as a Grignard reagent, for example giving an alcohol when added to a ketone.<\/p>\n<\/div>\n<\/div>\n<div id=\"section_19\">\n<div id=\"section_4\" class=\"mt-section\">\n<p>Grignard reagents will not react efficiently in S<sub>N<\/sub>2 reactions with alkyl halides (the Gilman reagent, described below, can be used for this purpose).<\/p>\n<div>\n<div class=\"mt-section\">\n<h3 class=\"editable\">Contributors<\/h3>\n<ul>\n<li><a title=\"http:\/\/chemwiki.ucdavis.edu\/Organic_Chemistry\/Organic_Chemistry_With_a_Biological_Emphasis\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Book%3A_Organic_Chemistry_with_a_Biological_Emphasis_(Soderberg)\" rel=\"internal\"><strong>Organic Chemistry With a Biological Emphasis <\/strong><\/a>by\u00a0<a class=\"external\" title=\"http:\/\/facultypages.morris.umn.edu\/~soderbt\/\" href=\"http:\/\/facultypages.morris.umn.edu\/%7Esoderbt\/\" target=\"_blank\" rel=\"external nofollow noopener\">Tim Soderberg<\/a>\u00a0(University of Minnesota, Morris)<\/li>\n<\/ul>\n<header><\/header>\n<header><\/header>\n<header><\/header>\n<header>\n<h2 class=\"editable\">20.3.4. Reactions of organocuprates (Gilman Reagents)<\/h2>\n<\/header>\n<section class=\"mt-content-container\">\n<div id=\"skills\">\n<div class=\"textbox learning-objectives\">\n<h3>Learning Objectives<\/h3>\n<div id=\"skills\">\n<p>After completing this section, you should be able to<\/p>\n<ol>\n<li>write an equation for the formation of an alkyllithium from an alkyl halide.<\/li>\n<li>write an equation for the formation of a lithium dialkylcopper (Gilman) reagent from an alkyllithium and copper(I) iodide.<\/li>\n<li>write an equation for the coupling of a lithium dialkylcopper reagent with an alkyl halide (i.e., a Corey-House synthesis).<\/li>\n<li>draw the structure of the product formed from a given Corey-House synthesis.<\/li>\n<li>identify the reagents needed to convert two given organohalides to a specified hydrocarbon through a Corey-House synthesis.<\/li>\n<\/ol>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"section_2\" class=\"mt-section\">\n<h3 class=\"editable\">Preparation of Gilman reagents<\/h3>\n<p>The Gilman reagent is a lithium diorganocopper species that can be prepared from organolithium compounds:<\/p>\n<p><img decoding=\"async\" class=\"\u201cinternal internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28171249\/image151.png\" alt=\"image152.png\" width=\"464px\" height=\"37px\" \/><\/p>\n<h3>Coupling reactions of Gilman reagents with alkyl and acyl halides<\/h3>\n<p>Gilman reagents are useful in that, unlike Grignard reagents, they will efficiently react in S<sub>N<\/sub>2 reactions with alkyl halides, even when the halogen is bonded to an sp<sup>2<\/sup>-hybridized, alkene carbon (remember from <a title=\"Organic Chemistry\/Organic Chemistry With a Biological Emphasis\/Chapter 8: Nucleophilic substitution reactions I\/Section 2: Two mechanistic models for a nucleophilic substitution reaction\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Book%3A_Organic_Chemistry_with_a_Biological_Emphasis_(Soderberg)\/Chapter_08%3A_Nucleophilic_substitution_reactions_I\/8.2%3A_Two_mechanistic_models_for_a_nucleophilic_substitution_reaction\" rel=\"internal\">section 8.2C <\/a>that S<sub>N<\/sub>2 reactions typically do not occur at sp<sup>2<\/sup>-hybridized carbons!)<\/p>\n<p><img decoding=\"async\" class=\"\u201cinternal internal aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28171252\/image153.png\" alt=\"image154.png\" width=\"746px\" height=\"166px\" \/><\/p>\n<p>In general, we see:<\/p>\n<\/div>\n<div><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-2559 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/12203111\/download-22.png\" alt=\"\" width=\"624\" height=\"96\" \/><\/div>\n<div id=\"section_3\" class=\"mt-section\">\n<div class=\"textbox examples\">\n<h3>Examples<\/h3>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-2560 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/12203139\/download-3.png\" alt=\"\" width=\"568\" height=\"101\" \/><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-2562 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/12203214\/download-4.png\" alt=\"\" width=\"624\" height=\"138\" \/><\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-2561 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/12203211\/download-5.png\" alt=\"\" width=\"624\" height=\"152\" \/><\/p>\n<p>&nbsp;<\/p>\n<\/div>\n<\/div>\n<div id=\"section_4\" class=\"mt-section\">\n<div class=\"textbox exercises\">\n<h3>Exercises<\/h3>\n<ol>\n<li>Starting with alkyl halides containing no more than four carbon atoms, how would you synthesize each of the following alkanes?\n<ol>\n<li>2,5-dimethylhexane<\/li>\n<li>2-methylhexane<\/li>\n<\/ol>\n<\/li>\n<\/ol>\n<div id=\"section_5\" class=\"mt-section\">\n<h3 class=\"editable\">Answers<\/h3>\n<ol>\n<li><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-2564 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/12203454\/10-7a-answer.png\" alt=\"\" width=\"521\" height=\"267\" \/><\/li>\n<li><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-2563 aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/12203451\/10-7b-answer.png\" alt=\"\" width=\"470\" height=\"211\" \/><\/li>\n<\/ol>\n<p>&nbsp;<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/section>\n<section class=\"mt-content-container\">\n<div id=\"section_1\" class=\"mt-section\">\n<h3>Conjugate addition of Gilman reagents<\/h3>\n<p>Another useful reaction of organocuprates is the so-called &#8220;conjugate addition&#8221; to C=C-C=O compounds, often called .\u00a0 Whereas RMgX and RLi will simply add normally to the C=O of such compounds, the R<sub>2<\/sub>CuLi will add to the alkene portion rather than directly to the carbonyl:<\/p>\n<p><img decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170544\/15.jpg\" alt=\"15.jpg\" width=\"320px\" height=\"128px\" \/><\/p>\n<div class=\"textbox examples\">\n<h3>Examples<\/h3>\n<p><img decoding=\"async\" class=\"internal default aligncenter\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/28170546\/16.jpg\" alt=\"16.jpg\" width=\"403px\" height=\"111px\" \/><\/p>\n<\/div>\n<\/div>\n<\/section>\n<section class=\"mt-content-container\">\n<header>\n<section class=\"mt-content-container\">\n<div id=\"section_6\" class=\"mt-section\">\n<h3 class=\"editable\">Contributors<\/h3>\n<ul>\n<li><a class=\"external\" title=\"http:\/\/science.athabascau.ca\/staff-pages\/dietmark\" href=\"http:\/\/science.athabascau.ca\/staff-pages\/dietmark\" target=\"_blank\" rel=\"external nofollow noopener\">Dr. Dietmar Kennepohl<\/a> FCIC (Professor of Chemistry, <a class=\"external\" title=\"http:\/\/www.athabascau.ca\/\" href=\"http:\/\/www.athabascau.ca\/\" target=\"_blank\" rel=\"external nofollow noopener\">Athabasca University<\/a>)<\/li>\n<li>Prof. Steven Farmer (<a class=\"external\" title=\"http:\/\/www.sonoma.edu\" href=\"http:\/\/www.sonoma.edu\" target=\"_blank\" rel=\"external nofollow noopener\">Sonoma State University<\/a>)<\/li>\n<\/ul>\n<h3>Video<\/h3>\n<p>https:\/\/youtu.be\/a-ksnhFbTRs<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone size-thumbnail wp-image-3007\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/3773\/2018\/11\/08152957\/frame-38-150x150.png\" alt=\"\" width=\"150\" height=\"150\" \/><\/p>\n<\/div>\n<\/section>\n<\/header>\n<header><\/header>\n<\/section>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/section>\n<\/div>\n<\/section>\n<\/div>\n<\/section>\n<\/div>\n<\/section>\n<\/div>\n\n\t\t\t <section class=\"citations-section\" role=\"contentinfo\">\n\t\t\t <h3>Candela Citations<\/h3>\n\t\t\t\t\t <div>\n\t\t\t\t\t\t <div id=\"citation-list-1320\">\n\t\t\t\t\t\t\t <div class=\"licensing\"><div class=\"license-attribution-dropdown-subheading\">CC licensed content, Shared previously<\/div><ul class=\"citation-list\"><li>19.7 Nucleophilic Addition of Grignard Reagents and Hydride Reagents: Alcohol Formation. <strong>Authored by<\/strong>: Dr. Dietmar Kennepohl and Prof. Steven Farmer. <strong>Located at<\/strong>: <a target=\"_blank\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Map%3A_Organic_Chemistry_(McMurry)\/Chapter_19%3A_Aldehydes_and_Ketones%3A_Nucleophilic_Addition_Reactions\/19.07_Nucleophilic_Addition_of_Grignard_Reagents_and_Hydride_Reagents%3A_Alcohol_Formation\">https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Map%3A_Organic_Chemistry_(McMurry)\/Chapter_19%3A_Aldehydes_and_Ketones%3A_Nucleophilic_Addition_Reactions\/19.07_Nucleophilic_Addition_of_Grignard_Reagents_and_Hydride_Reagents%3A_Alcohol_Formation<\/a>. <strong>Project<\/strong>: Chemistry LibreTexts. <strong>License<\/strong>: <em><a target=\"_blank\" rel=\"license\" href=\"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/\">CC BY-NC-SA: Attribution-NonCommercial-ShareAlike<\/a><\/em><\/li><li>Grignard and Organolithium Reagents. <strong>Authored by<\/strong>: Prof. Steven Farmer and William Reusch. <strong>Located at<\/strong>: <a target=\"_blank\" href=\"https:\/\/chem.libretexts.org\/?title=Textbook_Maps\/Organic_Chemistry\/Supplemental_Modules_(Organic_Chemistry)\/Aldehydes_and_Ketones\/Synthesis_of_Aldehydes_%26_Ketones\/Grignard_and_Organolithium_Reagents\">https:\/\/chem.libretexts.org\/?title=Textbook_Maps\/Organic_Chemistry\/Supplemental_Modules_(Organic_Chemistry)\/Aldehydes_and_Ketones\/Synthesis_of_Aldehydes_%26_Ketones\/Grignard_and_Organolithium_Reagents<\/a>. <strong>Project<\/strong>: Chemistry LibreTexts. <strong>License<\/strong>: <em><a target=\"_blank\" rel=\"license\" href=\"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/\">CC BY-NC-SA: Attribution-NonCommercial-ShareAlike<\/a><\/em><\/li><li>10.7: Organometallic Coupling Reactions. <strong>Authored by<\/strong>: Dr. Dietmar Kennepohl and Prof. Steven Farmer. <strong>Located at<\/strong>: <a target=\"_blank\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Map%3A_Organic_Chemistry_(McMurry)\/Chapter_10%3A_Organohalides\/10.07_Organometallic_Coupling_Reactions\">https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Map%3A_Organic_Chemistry_(McMurry)\/Chapter_10%3A_Organohalides\/10.07_Organometallic_Coupling_Reactions<\/a>. <strong>Project<\/strong>: Chemistry LibreText. <strong>License<\/strong>: <em><a target=\"_blank\" rel=\"license\" href=\"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/\">CC BY-NC-SA: Attribution-NonCommercial-ShareAlike<\/a><\/em><\/li><li>17.5 Alcohols from Reaction of Carbonyl Compounds: Grignard Reagents. <strong>Authored by<\/strong>: Dr. Dietmar Kennepohl and Prof. Steven Farmer. <strong>Located at<\/strong>: <a target=\"_blank\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Map%3A_Organic_Chemistry_(McMurry)\/Chapter_17%3A_Alcohols_and_Phenols\/17.05_Alcohols_from_Reaction_of_Carbonyl_Compounds%3A_Grignard_Reagents\">https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Map%3A_Organic_Chemistry_(McMurry)\/Chapter_17%3A_Alcohols_and_Phenols\/17.05_Alcohols_from_Reaction_of_Carbonyl_Compounds%3A_Grignard_Reagents<\/a>. <strong>Project<\/strong>: Chemistry Libretexts. <strong>License<\/strong>: <em><a target=\"_blank\" rel=\"license\" href=\"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/\">CC BY-NC-SA: Attribution-NonCommercial-ShareAlike<\/a><\/em><\/li><li>Conversion to ketones using Grignard reagents. <strong>Authored by<\/strong>: Prof. Steven Farmer. <strong>Located at<\/strong>: <a target=\"_blank\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Supplemental_Modules_(Organic_Chemistry)\/Nitriles\/Reactivity_of_Nitriles\/Conversion_to_ketones_using_Grignard_reagents\">https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Supplemental_Modules_(Organic_Chemistry)\/Nitriles\/Reactivity_of_Nitriles\/Conversion_to_ketones_using_Grignard_reagents<\/a>. <strong>Project<\/strong>: Chemistry Libretexts. <strong>License<\/strong>: <em><a target=\"_blank\" rel=\"license\" href=\"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/\">CC BY-NC-SA: Attribution-NonCommercial-ShareAlike<\/a><\/em><\/li><li>Organic Chemistry With a Biological Emphasis . <strong>Authored by<\/strong>: Tim Soderberg. <strong>Located at<\/strong>: <a target=\"_blank\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Book%3A_Organic_Chemistry_with_a_Biological_Emphasis_(Soderberg)\/13%3A_Reactions_with_stabilized_carbanion_intermediates_I\/13.6%3A_Synthetic_parallel_-_carbon_nucleophiles_in_the_lab#13.6C:_Terminal_alkynes_as_carbon_nucleophiles\">https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Book%3A_Organic_Chemistry_with_a_Biological_Emphasis_(Soderberg)\/13%3A_Reactions_with_stabilized_carbanion_intermediates_I\/13.6%3A_Synthetic_parallel_-_carbon_nucleophiles_in_the_lab#13.6C:_Terminal_alkynes_as_carbon_nucleophiles<\/a>. <strong>Project<\/strong>: Chemistry Libretexts. <strong>License<\/strong>: <em><a target=\"_blank\" rel=\"license\" href=\"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/\">CC BY-NC-SA: Attribution-NonCommercial-ShareAlike<\/a><\/em><\/li><li>10.7: Organometallic Coupling Reactions. <strong>Authored by<\/strong>: Dr. Dietmar Kennepohl and Prof. Steven Farmer. <strong>Located at<\/strong>: <a target=\"_blank\" href=\"https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Map%3A_Organic_Chemistry_(McMurry)\/Chapter_10%3A_Organohalides\/10.07_Organometallic_Coupling_Reactions\">https:\/\/chem.libretexts.org\/Textbook_Maps\/Organic_Chemistry\/Map%3A_Organic_Chemistry_(McMurry)\/Chapter_10%3A_Organohalides\/10.07_Organometallic_Coupling_Reactions<\/a>. <strong>Project<\/strong>: Chemistry Libretexts. <strong>License<\/strong>: <em><a target=\"_blank\" rel=\"license\" href=\"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/\">CC BY-NC-SA: Attribution-NonCommercial-ShareAlike<\/a><\/em><\/li><li>Organocuprate reagents convert acid chlorides to ketones. <strong>Authored by<\/strong>: Prof. Steven Farmer. <strong>Located at<\/strong>: <a target=\"_blank\" 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