Grignard reagents conjugate addition reactions

Addition-elimination. Axially chiral l,l -biphenyl-2-carboxylate esters are obtained by the reaction of 2-menthoxybenzoates with aryl Grignard reagents. Conjugate addition followed by elimination of a malonic ester unit constitutes a useful method for the access to (Z)-alkenes. The reagents are 1,1-dimetalloalkanes. 

This work was initiated in 1988 when Villacorta et al.71a reported the asymmetric conjugate addition of a Grignard reagent to 2-cyclohexenone. This study showed that 1,4-adducts with 4-14% ee were obtained in the presence of aminotroponeimine copper complex.713 Enhanced results (74% ee) were obtained by adding HMPA or silyl halides.71b Several other copper complexes were also used for inducing asymmetric conjugate addition reactions. Moderate results were obtained in most cases when THF was used as the solvent and HMPA as the additive. 

The simple addition and the conjugate addition reactions compete with each other. Figure 11-23 shows an example of a reaction with both the simple addition and the conjugate addition products. In this reaction, an increase in the size of the alkyl group on the Grignard reagent leads to an increase in the yield of the conjugate addition product, while substitution on the C=C leads to an increase in the yield of the simple addition product. 

The related 6-trifluoromethyl-l,3-dioxin-4-ones underwent conjugate addition reactions with Gilman reagents, or with Grignards with copper(I) catalysis (Eq. 112). The 6-substituted compounds were also available, and were used to synthesise threonine and aZZo-threonine analogues [303]. Stark contrast between the behaviour of fluorinated and non-fluorinated compounds is revealed in Eq. (113). While benzylmagnesium chloride adds smoothly to the 6-methyl... 

Lipshutz, B. H. Hackmann, C. Conjugate addition reactions of allylic copper species derived from Grignard reagents synthetic and spectroscopic aspects./. Org. Chem. 1994, 59, 7437-7444. 

Inexpensive and readily available Grignard reagents and stable dinuclear Cu complexes have been used for the first time in catalytic enantioselective conjugate addition reactions to simple acyclic a -unsaturated methyl esters.95 These reactions have provided access to highly valuable -substituted chiral esters in good yields and with excellent enantioselectivities (up to 99% ee). 

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... 

Conjugate-addition Reactions of Grignard Reagents with a,)3-... 

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