Reduction Reformatsky reagents

Specific enol equivalents will be needed for both synthons (61) and (66), Since (61) is to give a double bond but (66) is to give an alcohol, the logical choices are a Wittig reagent - actually (67) - for (61) and a Reformatsky reagent for (66). The ester to aldehyde conversion (65 63) Is easiest by over-reduction and re-... 

Silylacetals of difluoroketene have an important synthetic potential and constitute an alternative to the Reformatsky reagent generated from ethyl bromodifluoroace-tate." They are prepared by reduction by a bromo-, iodo-di-, or trifluoroacetate in the presence of a trialky Isilylchloride. Despite the fact that they are difficult to prepare, they behave similar to their nonfluorinated analogues (aldolization reactions, conjugated addition, etc.) (Figure 2.27)." ... 

Reactions of different organometallic species with thiocarbonyi compounds have been extensively investigated and been shown to proceed both in a carbophilic and a thiophilic fashion. However, other reactions can be observed simultaneously such as reduction, double addition, coupling, deprotonation and formation of enesulfides1,226,423. A complex pattern appears in the reactions of thioketones with lithium or Grignard reagents424. The first application of Reformatsky reagents in C—C bond formation by reaction with... 

The Reformatsky reagents, i.e. zinc enolates of esters, undergo Ni catalysed cross-coupling with aryl halides.53 The Ni catalysed reaction of arylzincs with a-bromoacetates also permits a-arylation of esters54 (Scheme 11.13). However, a-alkenylation of enolates of ketones, aldehydes, and esters has been less satisfactory. Its further development is clearly desirable. Alternatively, a-alkenylation of a-iodoenones in conjunction with conjugate reduction discussed earlier should be considered. 

Cleavage can then be achieved by reduction to provide simple amines (Table 1.10, Entry 1), " or an additional point of diversity can be introduced by treating with an appropriate nucleophile such as a Grignard reagent (Table 1.10, Entry 2) " or Reformatsky reagent (Table 1.10, Entry 3). Alternatively, if carbonyl compounds are loaded onto supports via a benzotriazole, then multifunctional cleavage can be achieved by treatment with nucleophiles such as enolates or amines to provide diketones (Table 1.10, Entry 4) and ureas (Table 1.10, Entry 5), respectively. 

Sequential cross-coupling reactions of 2,4-dichloropurine 69 have been conducted. 2,6-Disubstituted purine 69 was cross-coupled with MeZnBr to give monosubstituted purine 70, which underwent Suzuki cross-coupling with phenylboronic acid to furnish disubstituted purine 71. Recently, the synthesis of 6-(2-hydroxyethyl)purines was developed based on the Negishi palladium-catalyzed cross-coupling reactions of 6-chloropurines with the Reformatsky reagent followed by reduction by sodium borohydride and treatment with manganese(IV) oxide. ... 

A partial reduction of O-protected chiral cyanohydrins is also possible by reaction with Reformatsky reagents (Blaise reaction). The primarily formed imino intermediates can be hydrolyzed under very mild conditions to give the enamines ( )-15, which yield by treatment with strong acids the tetronic acids (R)-16 (Scheme 9) [39,40]. 

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