Simmons-Smith Cyclopropanation Reaction

Charette, André B.; Beauchemin, André


Almost 30 years after Emschwiller prepared IZnCH2I, Simmons and Smith discovered that the reagent formed by mixing a zinc-copper couple with CH2I2 in ether could be used for the stereospecific conversion of alkenes to cyclopropanes. Nowadays, the Simmons-Smith cyclopropanation reaction is one of the most widely used reactions in the organic chemist’s arsenal for the conversion of olefins into cyclopropanes. This popularity is mainly due to the stereospecificity of the reaction with respect to the double bond geometry and its compatibility with a wide range of functional groups. The chemoselectivity of the reaction toward some olefins is excellent and very few side reactions are observed with functionalized substrates. The metal carbenoid is electrophilic in nature and electron-rich alkenes usually react much faster than electron-poor alkenes.

Furthermore, the ability to use proximal hydroxy or ether groups to dictate the stereochemical outcome of the CC bond forming process was recognized early on, and this unique property has been successfully exploited on numerous occasions. It has been recognized that halomethylmetal reagents are powerful synthetic tools for the stereoselective addition of a methylene unit to chiral acyclic allylic alcohols and allylic ethers. In addition, the use of halomethylzinc reagents in the presence of chiral additives is one of the few ways to cyclopropanate allylic alcohols efficiently and with good enantiocontrol.

Carbenoids can be divided into the following two classes: (1) those of general structure MCH2X and (2) those corresponding to M = CH2. This chapter is focused exclusively on the first class in which M = Zn, Sm, or Al. Although other metal carbenoids of type MCH2X, such as those derived from Cu, Cd, Hg, and In, have been reported to be effective reagents for the cyclopropanation of some olefins, they have been used only sporadically, and this review does not highlight these reactions. This chapter covers cyclopropanation reactions involving haloalkylzinc, aluminum, and samarium reagents published since the comprehensive chapter in Organic Reactions by Simmons that surveyed the literature up to 1973.