Methylenations

Methylenations are chemical transformations that introduce a methylene group (−CH2−) into a molecule, typically by converting a carbonyl group into an alkene bearing a terminal −CH2 unit. The process is widely used to convert aldehydes and ketones into vinyl derivatives, and in many cases to replace a carbonyl oxygen with a methylene linkage to form exocyclic methylenes.

The most traditional method is the Wittig methylenation, which uses a methylenetriphenylphosphorane ylide to react with aldehydes or ketones and yield alkenes such as RCH=CH2 after workup. This approach provides a direct route to terminal methylene-containing products or, with substituted substrates, to disubstituted alkenes while retaining control over the carbon framework.

A widely applied, alternative approach is the Tebbe-type methylenation, based on a titanocene-based carbenoid reagent. The Tebbe reagent transfers a CH2 unit to carbonyl compounds under relatively mild conditions, often accommodating sensitive substrates and providing exocyclic methylenes or vinylidene products. Other metal-based methylenation methods exist as variations on carbene or carbenoid chemistry, expanding substrate scope and enabling methylene transfer under different conditions.

Applications of methylenation span natural product synthesis, carbohydrate and polymer chemistry, and the construction of alkenes from carbonyl-containing precursors. While powerful, methylenation can face challenges such as functional group compatibility, stereochemical control in forming the double bond, and potential side reactions that require careful selection of reagents and conditions.