Grignard additions to unsaturated 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. 

Scheme 2 shows a related study of the regio- and stereochemistry of magnesium enolate addition to unsaturated ketones [22]. Enolates were generated by reaction of either mesityl or isopropyl Grignard reagent, or diisopropyl magnesium with ketones. 1,4-Addition was observed with the dienolate of t-butylacetone. Increased reaction temperature also lead to 1,4-addition. 

A linear analysis of the sinensals starts at the right hand end with a rehydration and a Grignard disconnection to ketone (70). This is y,5-unsaturated and so can be made by a Carroll rearrangement (Chapter 35) (remembering to invert the allylic alcohol). This allylic alcohol can again be made by vinyl Grignard addition to a ketone (64) already made for the convergent approach, ... 

Precursor y-halogeno alcohols are frequently prepared by the classic sequence of addition of hydrogen halide to a,/3-unsaturated aldehydes, ketones, acids or esters, followed by Grignard reaction or hydride reduction. Recently a novel and general synthesis of 3-methoxyoxetanes from 3-phenylseleno-2-propenal was reported. This method comprises a sequence of Grignard addition to the aldehyde function, treatment with two equivalents of MCPBA, and then reaction with methanolic sodium hydroxide (equation 78) (80JOC4063). 

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. 

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 y.,(i-unsaturated ketones.1 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... 

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