Asymmetric additions using diorganozincs

Herein, we describe highly enantioselective and diastereoselective additions of diorganozincs to aldehydes, imines, and enones. Enantioselective cyclo-propanation of allylic alcohols will also be mentioned. 

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The Reformatsky reaction,uncatalysed reactions of zinc organometallics, asymmetric additions using diorganozincs have been reviewed. 

The direct hydrozincation of olefins14 is possible using Et2Zn in the presence of catalytic amount of Ni(acac)2 and 1,5-cyclooctadiene (COD). The resulting diorganozincs can be used for asymmetric additions to aldehydes. The best hydrozincation reactions are obtained with allylic alcohols or amines. In these cases the raction is driven to completion by the formation of a zinc-heterocycle of type 7 (Scheme 5.10). 

Diorganozincs can also be prepared by a nickel-catalyzed hydrozincation. The reaction of Et2Zn with Ni(acac)2 may produce a nickel hydride that adds to an alkene leading after transmetallation with Et2Zn to a diakylzinc (Scheme 9). This reaction proceeds in the absence of solvent and at temperatures of 50-60 °C. A number of functionalized olefins like allylic alcohols or amines can be directly used. This method is especially well suited for the preparation of functionalized diorganozincs for the asymmetric addition to aldehydes (Equation (45)).108,50... 

Cyclopropylcarbinols are prepared from dicyclopropylzinc, and t)ie use of mixed diorganozincs such as MejSiCHjZnEt for the addition has also been explored. Chiral tertiary alcohols are obtained from organozinc addition to ketones in the presence of functionalized isobomeols. (15,2/f)-2-(A -piperidinyl)-l-phenylpropane-l-thiol acetate is a ligand prepared from (+)-norephedrine ° and it catalyzes asymmetric addition of diethylzinc to aldehydes very effectively. 

Woodward et al. have used the binaphthol-derived ligand 40 in asymmetric conjugate addition reactions of dialkylzinc to enones [46]. Compound 40 has also been studied as a ligand in allylic substitutions with diorganozinc reagents [47]. To allow better control over selectivity in y substitution of the allylic electrophiles studied, Woodward et al. investigated the influence of an additional ester substituent in the jS-position (Scheme 8.25). 

Immobilization of chiral ligands to effect asymmetric induction in alkylation of aromatic aldehydes by diorganozinc reagents promoted by PEG-im-mobilized ligands 54-57 can also be promoted by soluble polystyrene-bound species. A recent example of this is work where a polystyrene-bound BINOL was prepared [ 105]. This polymer 69 was used to form titanium-BINOLate and AlLibis(binaphthoxide) catalysts for Et2Zn reaction with benzaldehyde and for asymmetric Michael additions of stabilized carbanions to cyclohexenone. While good stereoselectivities were obtained with these catalysts, the synthetic yields were modest. 

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