Ketones, unsaturated Grignard reagents

The synthetic application of organocopper compounds received a major impetus from the study of the catalytic effect of copper salts on reactions of Grignard reagents with a,j5-unsaturated ketones. Whereas Grignard reagents normally add to conjugated enones to give the 1,2-addition product, the presence of catalytic amounts of Cu(I) results in... 

The Grignard reagent attacks the unsaturated ketones (3) and (6) from the relatively unhindered ot- or jS-side, respectively, perpendicular to the plane of the conjugated system. An analogous transition state (10) leading to axially substituted 1,6-addition products (11) from A -3-ketones (9) with methylmagnesium halide was suggested by Marshall. ... 

The addition of Grignard reagents to unsaturated ketones gives mixtures resulting from 1,2-addition and 1,4-addition. In the presence of cuprous salts, however, the conjugate (1,4) addition is enhanced to the extent that the reaction becomes synthetically useful (11). Two examples of this procedure are given. 

Conjugate addition of an alkyl group to an c /S-unsaturated ketone (but not aldehyde) is one of the more useful 1,4-addition reactions, just as direct addition of a Grignard reagent is one of the more useful 1,2-additions. 

Reaction of a-sulphinyl carboxylic esters 421 with carbonyl compounds has usually been performed using a Grignard reagent as a base. No condensation products are obtained using f-butyllithium or sodium hydride - (equation 251). The condensation products formed are convenient starting materials for the synthesis of a, ) -unsaturated esters and j -ketones . ... 

Finally, Holm and 0gaard Madsen (1992) determined the secondary /3-deuterium KIEs for the addition of /3-deuterated Grignard reagents to unsaturated ketones. Hie authors attributed the small, <5%, KIEs they found in these radical reactions to opposing steric and hyperconjugative effects. 

The reaction of hexafluoropropene oxide (HFPO) (90) with excess Grignard reagents formed alkylated a,/ -unsaturated ketones (91) (Scheme 33) [80]. 

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