Hydride transfer from Grignard reagents

One common side reaction during 1,2-addition of alltyl-Grignard reagents to reactive carbonyl compounds is reduction of the carbonyl via hydride transfer from the beta-carbon of the i-Pr group to form propene and the corresponding alcohol (Scheme 11.50). 

The heterocyclic derivative successfully protects the acid from attack by Grignard or hydride-transfer reagents. The carboxylic acid group can be regenerated by acidic hydrolysis or converted to an ester by acid-catalyzed reaction with the appropriate alcohol. 

On the basis of these observations the draft mechanism shown in Scheme 3.160 has been proposed for the catalytic reaction, by analogy with the previous reaction. The reaction of CoCl2(dpph) with M( jSiCH2MgOl gives complex 168, which is electron-rich, because of coordination of the Grignard reagent. Complex 168 effects single-electron transfer to an alkyl halide to yield an anion radical of the halide and cobalt complex 169. Immediate loss of halide from the anion radical affords an alkyl radical intermediate, which adds to styrene to yield a benzyl radical. Cobalt species 169 would then recombine with the carbon-centered radical to form cobalt species 170. Finally, /i-hydride elimination provides... 

Hydride-transfer reactions suffer from the several shortcomings. First, a conventional optical resolution must usually be performed to obtain an optically active carbinol, which is then converted to the halide when the Grignard method is to be used. The actual reduction is generally not the only reaction pathway hence carbinol by-product is produced. More undesirable, however, is the fact that the asymmetric center of the organometallic reagent is sacrificed when the new chiral center is created. Unless the reaction is stereospecific, which is rarely the case, a net overall decrease in chirality results. 

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