Introduction

Carbenes were once only thought of as short lived intermediates. The reactions of this section only deal with these short lived carbenes which are mostly prepared in situ, at the time of the main reaction. However, there do exist so called persistent carbenes, which are stabilized by a variety of methods often including aromatic rings or transition metals. In general a carbene is neutral and has six valence electrons, two of which are non bonding. These electrons can either occupy the same sp² hybridized orbital to form a singlet carbene (with paired electrons), or two different sp² orbitals to form a triplet carbene (with unpaired electrons), but we will focus exclusively on the more common singlet carbenes.

The reactivity of a singlet carbene is concerted and similar to that of electrophilic or nucleophilic addition. The highly reactive nature of carbenes leads to very fast reactions in which the rate determining step is generally carbene formation.

Preparation of methylene (:CH₂)

The preparation of methylene starts with the yellow gas diazomethane, CH₂N₂. Diazomethane can be exposed to light, heat or copper to facilitate the loss of nitrogen gas and the formation of the simplest carbene methylene. The process is driven by the formation of the nitrogen gas which is a very stable molecule.

Carbene reaction with alkenes

A carbene such as methylene will react with an alkene which will break the double bond and result with a cyclopropane. The reaction will usually leave stereochemistry of the double bond unchanged. As stated before, carbenes are generally formed during the reaction; hence the starting material is diazomethane not methylene.

In the above case cis-2-butene is converted to cis-1,2-dimethylcyclopropane. Likewise, below the trans configuration is maintained.

Other carbenes

In addition to the general carbene with formula R₂C: there exist a number of other compounds that behave in much the same way as carbenes in the synthesis of cyclopropane derivatives. Halogenated carbenes such as dichlorocarbene, Cl₂C:, are more stable than simple alkyl carbenes. Dichlorocarbene can be conveniently prepared from chloroform (CHCl₃) with base in the presence of a phase transfer catalyst:

These halogenated carbenes form cyclopropanes in the same manner as methylene:

Outside links

• http://en.wikipedia.org/wiki/Carbene

Problems

1. Knowing that cycloalkenes react much the same as regular alkenes what would be the expected structure of the product of cyclohexene and diazomethane facilitated by copper metal?

2. What would be the result of a reaction of diazomethane with trans-3-pentene in the presence of light?

3. What starting material could be used to form cis-1,2-diethylcyclopropane?

4. What would the following reaction yield?

Answers

1. The product will be a bicyclic ring, Bicyclo[4.1.0]heptane.

2. The stereochemistry will be retained making a cyclopropane with trans methyl and ethyl groups. Trans-1-ethyl-2-methylcyclopropane

3. The cis configuration will be maintained from reagent to product so we would want to start with cis-3-hexene. DIazomethane would be the carbene source, with methylene as the carbene.

4. The halogenated carbene will react the same as methylene yielding, cis-1,1-dichloro-2,3-dimethylcyclopropane.

References

1. Vollhardt, K. Peter C. and Schore, Neil E. Organic Chemistry: Structure and Function. New York: Bleyer, Brennan, 2007.
2. Abdel-Wahab, Aboel-Magd A. Ahmed, Saleh A. and Dürr, Heinz. “Carbene Formation by Extrusion of Nitrogen” in CRC Handbook of Organic Photochemistry and Photobiology. CRC Press, 2004.
3. Karty, J. Organic Chemistry: Principles and Mechanisms, First Edition.  W. W. Norton, 2014.

Halogen molecules such as Cl₂ and Br₂ also add to alkene double bonds. Here we need not be concerned with orientation since the two ends of the adding molecule are identical, but the electrophilic addition mechanism helps us understand another characteristic of this reaction, its stereochemistry.

If bromine is added to cyclopentene, we might anticipate two products which differ in how the bromine atoms are geometrically related to each other. If the two bromines are on the same face of the ring, the compound is called cis. If they are on opposite faces, the compound is called trans. The experimental result is that only the trans product is formed.

One of the bromine atoms is acting as an electrophile. If we apply the usual mechanism, its first step it would go like this:

As we learned in our study of S_N1 reactions, carbocations are attacked by nucleophiles on both faces. If a carbocation is present in this system, we’d expect to find both the cis and trans products.

This is not what happens when the experiment is done, so we conclude that the carbocation is not present, or it reacts immediately to form a new cation. Something is happening which prevents the nucleophilic bromide ion from attacking the face of the carbocation which already is attached to the first bromine. We understand that by envisioning that the electrophilic bromine atom attaches itself to both alkene carbon atoms. One bond is made using the electrons from the pi bond, and the other is made using an unshared electron pair from the bromine. This results in a new ring formed from the bromine and the two alkene carbon atoms. It is called a “bromonium” ion.  Note that the mechanism for forming the three-membered ring has some parallels with cyclopropanation, described above.

Attack by the nucleophilic bromide ion on the bromine in this ring would only result in cyclopentene and bromine, so no reaction would occur. Attack by the bromide ion on the either of the alkene carbons would be like an S_N2 reaction. The attacked carbon would invert, and the product would have the trans configuration. (Notice that there are two such products, which are enantiomers, so we get a racemic mixture.)

Khan Academy on alkene halogenation:

10.7.3. Oxymercuration-demercuration

Epoxide, also called oxiranes, are useful reagents that may be opened by further reaction to form anti vicinal diols. One way to synthesize epoxides is through the reaction of an alkene with a peroxycarboxylic acid such as MCPBA.

Mechanism

Peroxycarboxylic acids are generally unstable. One stable example is meta-chloroperoxybenzoic acid, shown in the mechanism below. Often abbreviated MCPBA, it is a stable crystalline solid that is popular for laboratory use. However, MCPBA can be explosive under some conditions.

Peroxycarboxylic acids are sometimes replaced in industrial applications by monoperphthalic acid, or the monoperoxyphthalate ion bound to magnesium, which gives magnesium monoperoxyphthalate (MMPP). In either case, a nonaqueous solvent such as dichloromethane, ether, acetone, or dioxane is used. This is because in an aqueous medium with any strong acid or base catalyst present, the epoxide ring is hydrolyzed to form a vicinal diol, a molecule with two OH groups on neighboring carbons. (For more explanation of how this reaction leads to vicinal diols, see below.)  However, in a nonaqueous solvent, the hydrolysis is prevented and the epoxide ring can be isolated as the product. Reaction yields from this reaction are usually good. The reaction rate is affected by the nature of the alkene, with more nucleophilic double bonds resulting in faster reactions.

Example

Since the transfer of oxygen is to the same side of the double bond, the resulting oxacyclopropane ring will have the same stereochemistry as the starting alkene. A good way to think of this is that the alkene is rotated so that some constituents are coming forward and some are behind. Then, the oxygen is inserted on top. (See the product of the above reaction.) One way the epoxide ring can be opened is by an acid catalyzed oxidation-hydrolysis. Oxidation-hydrolysis gives a vicinal diol, a molecule with OH groups on neighboring carbons. For this reaction, the dihydroxylation is anti since, due to steric hindrance, the ring is attacked from the side opposite the existing oxygen atom. Thus, if the starting alkene is trans, the resulting vicinal diol will have one S and one R stereocenter. But, if the starting alkene is cis, the resulting vicinal diol will have a racemic mixture of S, S and R, R enantiomers.