Gilman cuprates, conjugate addition

A similar explanation may also hold for the result of conjugate addition to y-phthalimido enoate 80 (Scheme 6.16). Thus, addition of the bulky cyano-Gilman silyl cuprate gave the syn diastereomer 81 (dr = 96 4) [32, 33]. Preference for the sterically least hindered nucleophile trajectory seems to dictate the overall stereochemical outcome (transition state 82). 

An interesting chromium system example is represented by complex 145. Addition of cyano-Gilman cuprates occurred with complete diastereoselectivity to give conjugate adducts 146 (Scheme 6.28). Interestingly, the opposite diastereomer was accessible by treatment of enone 145 with a titanium tetrachloride/Grignard reagent combination [71c]. 

As recently highlighted by Woodward, enantioselective Sf/2 allylic substitution reactions are mechanistically related to conjugate addition reactions . Theoretical studies carried out by Nakamura and coworkers for the conjugate addition and allylic alkylation using Gilman s cuprates revealed profound mechanistic similarities between these two processes . ... 

Scheme 10. Working hypothesis for the o-DPPB group to act as an organometallic reagent directing group for the conjugate addition of Gilman cuprates to acyclic enoates.

Pyridylmethyllithium species generally react as hard anions giving rise to 1,2-addition products when coupled with a,/3-unsaturated carbonyl derivatives. It has been found that the corresponding cyano-Gilman cuprates such as 42 also undergo 1,2-addition to a,/3-unsaturated ketones but do add in a conjugate fashion to cr,/3-unsaturated esters and lactones such as 43 in good yield and stereoselectivity <200314(60) 1843> (Scheme 7). 

The copper-catalyzed 1,4-addition of Grignard reagents to enones has been described by Kharasch in 1941, that is, one decade before the discovery of Gilman cuprates (1952) and more than two decades before the first use of organocuprates in conjugate addition reactions. Consequently, numerous variations and applications of the method have been reported over the years.3 5,7 7a 23 Not surprisingly, several of the advances made in the last decade with... 

Kharasch and Tawney (1941) reported that copper salts catalyze 1,4-addi-tion of Grignard reagents to a,jS-unsaturated ketones. Gilman et al. (1952) first discovered that phenylcopper reacts with benzalacetophenone in a 1,4-addition. Subsequently House and associates (1966) have revealed the scope of the conjugate addition of cuprate complexes. Now alkyl, vinyl, and aryl groups can be introduced specifically at the p position of a,jS-unsaturated carbonyl compounds. Transfer of an allyl group from lithium diallylcuprate to 2-cyclohexenone is also known (House and Fischer, 1969). However, ethynyl, cyano, and hetero groups attached to the copper atom are difficult to transfer to electron-poor olefins. 

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