Simmons–Smith reaction

In the Simmons–Smith reaction the reactive carbenoid is iodomethylzinc iodide, which is typically formed by a reaction between diiodomethane and a zinc-copper couple. Modifications involving cheaper alternatives have been developed, such as dibromomethane^[3] or diazomethane and zinc iodide.^[4] The reactivity of the system can also be increased by exchanging the zinc‑copper couple for diethylzinc.^[5] Asymmetric versions are known.^[6]

Using diazo compounds

Certain diazo compounds, such as diazomethane, can react with olefins to produce cyclopropanes in a 2 step manner. The first step involves a 1,3-dipolar cycloaddition to form a pyrazoline which then undergoes denitrogenation, either photochemically or by thermal decomposition, to give cyclopropane. The thermal route, which often uses KOH and platinum as catalysts, is also known as the Kishner cyclopropane synthesis after the Russian chemist Nikolai Kischner^[7][8] and can also be performed using hydrazine and α,β-unsaturated carbonyl compounds.^[9] The mechanism of decomposition has been the subject of several studies and remains somewhat controversial, although it is broadly thought to proceed via a diradical species.^[10][11] In terms of green chemistry this method is superior to other carbene based cyclopropanations; as it does not involve metals or halogenated reagents, and produces only N₂ as a by-product. However the reaction can be dangerous as trace amounts of unreacted diazo compounds may explode during the thermal rearrangement of the pyrazoline.

Using diazo compounds with metal catalysis

Methyl phenyldiazoacetate and many related diazo derivatives are precursors to donor-acceptor carbenes, which can be used for cyclopropanation or to insert into C-H bonds of organic substrates. These reactions are catalyzed by dirhodium tetraacetate or, more spectacularly, related chiral derivatives.^{[12] [13][14]}

Using free carbenes

Free carbenes can be employed for cyclopropanation reactions, however there is limited scope for this as few can be produced conveniently and nearly all are unstable (see: carbene dimerization). An exception are dihalocarbenes such as dichlorocarbene or difluorocarbene, which are reasonably stable and will react to form geminal dihalo-cyclopropanes.^[15] These compounds can then be used to form allenes via the Skattebøl rearrangement.

The Buchner ring expansion reaction also involves the formation of a stabilised carbene. Cyclopropanation is also stereospecific as the addition of carbene and carbenoids to alkenes is a form of a cheletropic reaction, with the addition taking place in a syn manner. For example, dibromocarbene and cis-2-butene yield cis-2,3-dimethyl-1,1-dibromocyclopropane, whereas the trans isomer exclusively yields the trans cyclopropane.^[16]