Stereochemistry Simmons-Smith cyclopropanation

Corey exploited the remarkable configurational stability of cyclopropyllithiums in his synthesis of hybridalactone. The stannane 28 was made by Simmons-Smith cyclopropanation of the allylic alcohol 27 and resolved by formation of an O-methyl mandelate ester. Transmetallation of 29 with 2 equiv. BuLi gave an organolithium which retained its stereochemistry even in THF over a period of 3 h at 0 °C, finally adding to 31 to give 32. 

The Simmons-Smith cyclopropanation reaction Stereochemically controlled epoxidations Regio- and Stereocontrolled Reactions with Nucleophiles Claisen-Cope rearrangements Stereochemistry in the Claisen-Cope rearrangement The Claisen-Ireland rearrangement Pd-catalysed reactions of allylic alcohols Pd-allyl acetate complexes Stereochemistry of Pd-allyl cation complexes Pd and monoepoxides of dienes The control of remote chirality Recent developments Summary... 

There has been an extended account of the synthesis of racemic cyclopropanes of type 177, where Simmons-Smith cyclopropanation, followed by Mitsunobu coupling, were used to obtain the correct relative stereochemistry.202 a similar approach was used in Altmann s laboratory to convert the chiral unit 178, derived from D-ribonolactone, into the thymidine analogue 179. This compound was shown by X-ray analysis to adopt a 2 -exo- conformation, and this led to increased stability of RNA/DNA duplexes when 179 was incorporated into... 

Chemo- and stereoselective reduction of (56) to (55) is achieved In highest yield by sodium borohydride in ethanol. The isolated ketone is reduced more rapidly than the enone and (55) is the equatorial alcohol. Protection moves the double bond out of conjugation and even the distant OH group in (54) successfully controls the stereochemistry of the Simmons-Smith reaction. No cyclopropanation occurred unless the OH group was there. Synthesis ... 

However, this method really hit the headlines when it was used on allylic alcohols 61 and became known as the Simmons-Smith reaction.15 If there is stereochemistry at the alcohol 63, the cyclopropane is formed on the same side as the OH group 64 suggesting that the alcohol guides the zinc carbenoid into the alkene. 

All these methods using carbenes, metal complexes of carbenes or carbenoids are stereospecific in that the geometry of the alkene is faithfully reproduced in the stereochemistry of the cyclopropane so trans-61 gives trans-68 specifically. They can also be stereoselective, particularly the Simmons-Smith on allylic alcohols thus the cyclopropane in 68 is on the same side of the alkene as the OH group in 67. We now come to a widely used method that is not stereospecific on the alkene. 

The mechanism for the formation of this carbenoid and for its reaction with alkenes need not concern us here. Just remember that it reacts as though it is methylene. The Simmons-Smith reaction is an excellent way to prepare cyclopropane derivatives from alkenes, as shown in the following examples. Note the stereochemistry in the second equation. 

On the subject of stereochemistry, note that the Simmons-Smith zinc carbenoid behaves like a singlet carbene— its additions to alkenes are stereospecffic (the product cyclopropane retains the geometry of the aikene) as well as stereos elective (die carbenoid adds to the same face as the hydroxyl group). 

When Ireland wanted to introduce a cyclopropane ring stereoselectively into a pentacyclic system containing an enone, he first reduced the ketone to an alcohol (DIBAL gave only the equatorial alcohol) that controlled the stereochemistry of the Simmons-Smith reaction. Oxidation with Cr(VI) put back the ketone. 

Cyclopropanation. Irradiation (350 nm.) of CH2I2 in the presence of alkenes yields the corresponding cyclopropane adducts with complete retention of stereochemistry. The reaction is facilitated by increasing alkyl substitution in contrast to the Simmons-Smith reagent, this reaction is not sensitive to steric factors. Presumably methylene ( CH2) is the reactive species. ... 

General Methods.—Alternative procedures to that of Simmons-Smith for the synthesis of cyclopropanes from alkenes seem endless. Pienta and Kropp have now established that simple irradiation of gem-dihalides in the presence of alkenes produces the corresponding cyclopropane in excellent yields. Moreover, the method shows little sensitivity to steric effects and, perhaps surprisingly, proceeds with complete retention of stereochemistry, e.g. (2) - (3). 

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