Organozinc reagents regioselectivity

The first asymmetric procedure consists of the addition of R2Zn to a mixture of aldehyde and enone in the presence of the chiral copper catalyst (Scheme 7.14) [38, 52]. For instance, the tandem addition of Me2Zn and propanal to 2-cyclohexenone in the presence of 1.2 mol% chiral catalyst (S, R, R)-1S gave, after oxidation of the alcohol 51, the diketone 52 in 81% yield and with an ee of 97%. The formation of erythro and threo isomers is due to poor stereocontrol in the aldol step. A variety of trans-2,3-disubstituted cyclohexanones are obtained in this regioselective and enantioselective three-component organozinc reagent coupling. 

For each class of organozinc reagents, the corresponding possible substrates will be indicated and the issues concerning regioselectivity, either with respect to the substrate or the reagent, diastereoselectivity and in some cases enantioselectivity will be discussed. 

Besides the issues associated with the regioselectivity and stereoselectivity of these reactions, there is also one particular point of consideration in the case of substituted allylic organozinc reagents which deals with the metallotropic equiUbrium of such species. Indeed, each regio- or stereoisomer of a substituted allylic organozinc can in principle give rise to a different carbometallation product. 

One of the first reports dealing with the carbozincation of alkenes by allylic organozinc reagents was the addition of allylzinc bromide to the homoallylic amine 118 which occurred in refluxing THF. A secondary organozinc 119 was regioselectively produced and provided the amine 120 after hydrolysis. A small amount of aminoalcohol 121, resulting from oxidation of 119, was also isolated when the reaction mixture was exposed to air (equation 52)80,81. 

As a general rule, allylic organozinc reagents do not react with unactivated a, ji-disubstituted alkynes. A few exceptions to this trend have been observed in the case of substrates bearing an appropriately located heteroatom such as the homopropargylic tertiary amine 147. The latter reacted regioselectively with allylzinc bromide but led to a 67/33 mixture of two geometric isomers, apparently derived from syn and anti additions (equation 71)82,105. 

This reaction was successfully applied to various hydrazones derived from acyclic or cyclic ketones and extended to a variety of unsubstituted vinylsilanes as acceptors (trialkyl, triphenyl and alkoxy vinylsilanes). In all cases, the regioselectivity of the addition reaction was consistent with the formation of a silicon-stabilized organozinc reagent. 

S 2 -Ally lotion of R n or RZnCl. Cinnamyl chloride reacts with a variety of organozinc reagents in the presence of this Cu(I) reagent (5 mole %) at 20° to give the SN2 -products of allylation. The regioselectivity is comparable to that of RCu-BF3 at -70°. 

Addition to C O bond. Excellent regioselective addition of organozinc reagents to one of the C=0 group of a cyclic anhydride (see equation below) can be attributed to precoordination to the electronically more favorable double bond. ... 

Preparations. Functionalized organozinc reagents have been prepared from alkenes via stereoselective and regioselective hydroboration and B-Zn exchange. An interesting synthesis of carboxylic acids by chain extension from (o)-l)-unsaturated acids involves prior attachment to a resin (in the form of polymeric esters). ... 

Scheme 26 Regioselective alkylation of pyridines with Grignards and organozinc reagents.

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