SimmonsSmith

The Simmons–Smith reaction is a method for cyclopropanating alkenes by transferring a methylene unit from diiodomethane (CH2I2) in the presence of a zinc–copper couple or diethylzinc. Developed in the 1950s, it provides a practical route to cyclopropane rings under relatively mild conditions and with generally good stereochemical control.

The reaction proceeds through in situ generation of a methylene carbenoid, typically described as a CH2ZnI species, from CH2I2 and zinc (often activated with copper) or from diethylzinc. This carbenoid adds to the alkene in a concerted, syn fashion, producing the cyclopropane without significant loss of the alkene’s stereochemistry. In many cases the geometry of the original double bond is preserved in the cyclopropane. Coordination of the zinc carbenoid to adjacent functional groups, especially allylic or homoallylic alcohols, can direct the approach and enhance diastereoselectivity in what is known as directed Simmons–Smith cyclopropanation.

Variants and scope: The classical method uses CH2I2 with Zn/Cu in ether solvents. An alternative uses diethylzinc (Et2Zn) as the methylene donor, which can offer practical advantages for certain substrates and functional groups. Directed Simmons–Smith conditions exploit nearby hydroxyl groups to achieve high diastereoselectivity, particularly for homoallylic alcohols. While broadly applicable to a range of simple and functionalized alkenes, highly substituted alkenes or substrates bearing strongly coordinating functionalities may require special conditions or alternative cyclopropanation strategies.

Applications: The Simmons–Smith reaction is a staple in organic synthesis for constructing cyclopropane rings, frequently used in natural product synthesis, medicinal chemistry, and the elaboration of complex molecular architectures.