Simmons-Smith reaction, olefin cyclopropanation

The cyclopropanation of 1-trimethylsilyloxycyclohexene in the present procedure is accomplished by reaction with diiodomethane and diethylzinc in ethyl ether." This modification of the usual Simmons-Smith reaction in which diiodomethane and activated zinc are used has the advantage of being homogeneous and is often more effective for the cyclopropanation of olefins such as enol ethers which polymerize readily. However, in the case of trimethylsilyl enol ethers, the heterogeneous procedures with either zinc-copper couple or zinc-silver couple are also successful. Attempts by the checkers to carry out Part B in benzene or toluene at reflux instead of ethyl ether afforded the trimethylsilyl ether of 2-methylenecyclohexanol, evidently owing to zinc iodide-catalyzed isomerization of the initially formed cyclopropyl ether. The preparation of l-trimethylsilyloxybicyclo[4.1.0]heptane by cyclopropanation with diethylzinc and chloroiodomethane in the presence of oxygen has been reported. "... 

Addition of TCS 14 to CH2l2/Zn, which contains up to 0.04 mol% of lead impurity, improves the Simmons-Smith reaction of olefins such as cyclooctene to give up to 96% of the cyclopropane 2103 [36] (Scheme 13.12). 

Furthermore, cyclopropane structures have often served as intermediates in organic synthesis. For these reasons, olefin cyclopropanation has proved to be a useful tool for synthetic organic chemists. This has led to the development of several methods for cyclopropanation reactions,91 including the metal-catalyzed reactions of diazo compounds with olefins, as well as the Simmons-Smith reaction. 

Asymmetric cyclopropanation of olefins can also be achieved by the Simmons-Smith reaction (231). Reaction of ( )-cinnamyl alcohol and the diiodomethane-diethylzinc mixed reagent in the presence of a small amount of a chiral sulfonamide gives the cyclopropylcarbinol in up to 75% ee (Scheme 97) (232a). ( )-Cinnamyl alcohol can be cyclopro-... 

Cyclopropanes are commonly synthesized with Zn(CH2I)2 (37) using the Simmons-Smith-reactum.16 This reaction proceeds via one-step addition of one of the methylene groups of the zinc reagent to olefins. As an advantage of the Simmons-Smith-reaction no free carbene is involved. 

Cyclopropanation of olefins (Simmons-Smith reaction) smoothly proceeds using diethylzinc in combination with diiodomethane. The reaction is much faster with allylic alcohols or its ether derivatives than that with simple olefins. 

Electrochemical cyclopropanation of alkenes occurs using dibromomethanes at a sacrificial zinc electrode in a CH2C12/DMF mixture with a one compartment cell (equation 65). Yields using more than twenty isolated and conjugated olefins were generally good (30 to 70%)98. Benzal halides give only poor yields in the same reaction, but 2,2-dibromo-propane leads to the equivalent gem-dimethylcyclopropanes in fair yields. The method represents a useful alternative to other methods of cyclopropanation of olefins such as the Simmons-Smith reaction. 

The Simmons-Smith reaction is a powerful method for preparing cyclopropanes from olefins using zinc carbenoids (IZnCH2I, EtZnCH2I, Zn(CH2X)2).7a,278,278a A variety of versions of this reaction have been developed and new carbenoids species have been made. For recent reviews, see Ref 279 and 279a. 

Polymerization. Monomers. The cyclopropane type monomers are prepared either by addition of the dichlorocarbene or by the Simmons-Smith reaction on the corresponding olefins. Most of these compounds have been described. Spiropentane is prepared by the Applequist method (I, 2), by the reaction of zinc with C(CH2Br)4 in alcohol in the presence of ethylenediaminetetraacetic acid (EDTA). This hydrocarbon is purified until a single NMR signal is obtained at t = 9.28. 

A cis addition mechanism is generally accepted for the reaction, because cis addition to an olefinic bond generally occurs with predominant attack at trans bonds, and the Simmons-Smith reagent attacks preferentially one of the trans olefinic bonds of trans,trans,cis-1,5,9-cyclodode-catriene and then the cis double bond of the monoadduct (378). The close correspondence in relative rates of olefins for the cyclopropane formation by the Simmons-Smith reaction with those for diimide reduction and peroxide epoxidation supports the concept 409). The latter two reactions are generally considered to proceed via cis addition. 

The presence of ether functions in olefins frequently facilitates the Simmons-Smith reaction 457). For example, l-(o-methoxyphenyl)-propene gives a higher yield of a cyclopropane than the meta and para isomers, and coordination of (I) with ether oxygen was suggested 42, 457). 

Simmons-Smith reaction. Stereospecific synthesis of cyclopropanes by treatment of olefins with methylene iodide and zinc-copper couple. 

Besides Cu and Rh, various other metals are known to catalyze the decomposition of diazo compounds [6,7,8,9,10]. Palladium complexes, e.g., are efficient catalysts for the cyclopropanation of electron-deficient C-C double bonds with diazoalkanes [19,20, 21], in contrast to Cu and Rh catalysts which are better suited for reactions with electron-rich olefins. Unfortunately, attempts to develop chiral Pd catalysts for enantioselective cyclopropanation have not been successful so far [22]. More promising results have been obtained with cobalt and ruthenium complexes. These and other chiral metal catalysts, that have been studied besides Cu and Rh complexes, are discussed in chap. 16.3. The same chapter also covers a new direction of research that has recently been taken with the development of catalytic enantioselective Simmons-Smith reactions. 

Methylene iodide and a zinc-copper couple react in ether solution to give bis-(iodomethyl)zinc zinc iodide . Closely related reagents are accessible by the reaction of zinc halides with diazomethane . These reagents have been widely used in the synthesis of cyclopropanes from olefins. Norcarane formation from cyclohexene and bis(iodomethyl)zinc was found to be second order, k = (6.3 0.5) x 10 l.mole . sec " at 0°C These findings cannot be reconciled with the intermediacy of free methylene. A one-step methylene transfer mechanism has therefore been proposed for the Simmons-Smith reaction, viz. 

The Simmons-Smith reaction is the conversion of olefins to cyclopropanes by the use of halomethylzinc halides or related agents. Charette et al. found that a catalytic amount of chiral titanium-TADDOLate complex 78 was able to induce an enantioselective cyclopropanation of allylic alcohols. After optimisation of the catalytic structure, good yields and enantioselec-tivities were obtained, especially when 3-aryl and 3-heteroaiyl substituted allylic alcohols were used (Scheme 7.47). However, the reaction required the use of a high catalyst loading (25 mol%). 

In the absence of a directing group, the cyclopropanation of cyclic olefins is generally under steric control. The stereochemical preference can be predicted from the ground state conformation of the molecule and often high levels of stereocontrol are observed. For example, Paquette and coworkers used a Simmons-Smith reaction in their total synthesis of the secondary marine metabolite (+)-acetoxycrenulide (30), whereby high P-face selectivity was observed. ... 

Cycloaddition Reaction. Cyclopropanes can be prepared from a variety of olefins and dihalo compounds using a copper catalyst and moderate temperatures (70 °C). The reaction is a convenient extension of the conventional Simmons-Smith reaction.Lithium 2,2,6,6-tetramethylpiperidide gives superior yields to methyl lithium in the synthesis of alkoxycyclopropanes and cyclopropenes. In the latter examples no base-induced isomerization of the double bond to the exo-position is observed (Scheme 42)T >9... 

If this reaction is carried out in the presence of olefins, then cyclopropanes are obtained, often in good yield, by a methylene transfer process (the Simmons-Smith reaction). In the absence of olefin, ethylene is the main product ... 

Low intensity ultrasound has also been applied to the Simmons-Smith cyclopropanation of olefins with zinc-diiodomethane (237). This reaction normally will not occur without activation of mossy Zn with I2 or Li, and was difficult to scale-up due to delayed initiation. Yields upon sonication are nearly quantitative, activation of the Zn is unnecessary, and no delayed exotherms are observed. In reactions with another class of organic dihalides, ultrasonic irradiation of Zn with a,a -dibromo-o-xylene has proved a facile way to generate an o-xylylene-like species [Eq. (49)],... 

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