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 focussed 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.


Keywords:

Simmons-Smith reaction;
cyclopropanation;
mechanism;
haloalkylmetal reagents;
zinc carbenoids;
aluminum carbenoids;
samarium carbenoids;
in situ formation;
scope;
limitations;
solid state;
solution;
theoretical studies;
achiral alkenes;
intramolecular;
acyclic chiral alkenes;
cleavable chiral auxiliaries;
allylic compounds;
chiral acetals;
chiral allylic compounds;
unsaturated acylmetals;
chiral enol ethers;
chiral vinylboronates;
chiral enamines;
chiral additives;
chiral catalysts;
functional group;
side reactions;
comparison of methods;
experimental conditions;
experimental procedures;
tabular survey

Simmons‐Smith Cyclopropanation Reaction

Enantioselective Preparation of β,β‐Disubstituted α‐Methylenepropionates by MAO Promotion of the Zinc Schlenk Equilibrium

Publisher Summary This chapter describes the developments mainly after 1960 in synthetic reactions using organozinc compounds. The reaction of the triplet carbene with olefins gives cyclopropane derivatives in a nonstereospecific way and is accompanied by hydrogen abstraction, because the triplet carbene is a biradical. The presence of ether functions in olefins frequently facilitates the Simmons–Smith reaction. The reaction of phenanthrene with zinc dust and methylene iodide in 1, 2-dimethoxyethane gives 9,10 dihydro–9,10–methanophenanthrene (XIX) in 25% yield. Ring expansion of aromatic compounds by carbene, carbethoxycarbene, chlorocarbene, and carbenoid is well known. The reaction of aldehydes with the Simmons–Smith reagent in the presence of an excess amount of zinc dust gives the corresponding olefins in 29–63% yields. The reaction of the Simmons–Smith reagent with a carbon–carbon triple bond gives cyclopropene and its isomers along with small amounts of allene derivatives. Zinc carbenoids do not insert into olefinic C–H bonds, although the Simmons–Smith reagent was reported to attack ether to give products resulting from the insertion of a methylene group into the α–C–H bond. Organozinc reagents are generally much less reactive than Grignard reagents and organolithium reagents in addition reactions with carbonyl and other unsaturated compounds. The reaction of a carbonyl compound with an α–haloester in the presence of zinc is commonly known as the Reformatsky reaction. Allylic, benzylic, propargylic, and related organic halides react with many aldehydes and ketones in the presence of zinc to form alcohols.

Organozinc Compounds in Synthesis

16 – Zinc and Cadmium

This paper examines the speciation of ZnMe2, ZnMeCl, and ZnCl2 in tetrahydrofuran (THF) solution, and provides experimental (infrared (IR) and calorimetric experiments) and density functional theory (DFT) data to conclude that the species in THF solution are, beyond a doubt, ZnMe2(THF)2, ZnMeCl(THF)2, and ZnCl2(THF)2. Consequently, coordinated THF should be used in DFT mechanistic calculations (e.g., Negishi reactions in THF). Naked or single THF coordinated molecules are virtually nonexistent in THF solutions. A cluster-continuum model for the solvent is recommended to obtain a more-correct representation. The presence or absence of THF produces a marked effect on the thermodynamics of the Negishi catalysis and a lesser effect on the kinetics of the transmetalation.

Speciation of ZnMe2, ZnMeCl, and ZnCl2 in Tetrahydrofuran (THF), and Its Influence on Mechanism Calculations of Catalytic Processes

Infrared and Raman spectra have been measured for dimethylzinc and diethylzinc in various ethers, and for ethylzinc iodide in diethyl ether. Infrared spectra are also reported for mixtures of dimethylzinc and diethylzinc with zinc chloride, bromide, and iodide in tetrahydrofuran. It is concluded that for all the alkylzinc halide systems the Schlenk equilibrium lies predominantly on the side RZnX. The infrared spectra of a number of solid alkylzinc adducts have been measured, and the trends in the zinc–carbon stretching frequencies are briefly discussed.

D. F. Evans

Papers

The infrared and Raman spectra of alkylzinc halides and related compounds