Zinc enolates applications

They have developed direct asymmetric synthesis of quaternary carbon centers via addition-elimination process. The reactions of chiral nitroenamines with zinc enolates of a-substituted-8-lactones afford a,a-disubstituted-6-lactones with a high ee through addition-elimination process, in which (5)-(+)-2-(methoxy methy l)pyrrolidine (SMP) is used as a chiral leaving group (Eq. 4.96).119 Application of this method to other substrates such as a-substituted ketones, esters, and amides has failed to yield high ee. 

Tandem 1,4-addition to cycloalkenones constitutes an extremely versatile and elegant methodology for the synthesis of 2,3-disubstituted cycloalkanones, as is evident from its application in areas such as prostaglandin synthesis. Noyori et al. have reported the use of organozinc reagents in copper-catalyzed tandem additions [64]. The zinc enolate resulting from the catalytic enantioselective 1,4-addition of Et2Zn to cyclohexenone reacts readily with an aldehyde in a subsequent aldol condensation. 

Zinc enolates are exploited in a variety of synthetic applications where they are trapped by suitable electrophiles, particularly by carbonyl compounds. 

In this chapter attention will be focused on the different protocols recently developed to prepare zinc enolates, and on the most significant applications of these reactive intermediates in the field of organic synthesis. 

Preformed cyclic /V,A-dialkyliminium salts i.e. where a ring Joins the a-caibon and positively charged nitrogen) have been used in enolate condensation reactions. The number of examples, however, is rather limited, probably because of complications arising through abstraction of enolizable protons. A -Dehy-droindolizidinium salt (69) represents one of the few examples of an enolizable, cyclic A, -dialkylimi-nium salt known to react with an enolate (equation 8). The use of a soft zinc enolate in this reaction may be crucial. The relative stereochemistry of the resulting 3-amino ester (70) is undefined. /V-Alkyl-3,4-dihydroisoquinolinium salts e.g. 71), a class of nonenolizable, cyclic iminium salts, have had extensive applications in the total synthesis of protoberberine and phthalide isoquinoline alkaloids. A review by Pai and coworkers has covered much of this work. In a more recent application by Yamazaki and co-... 

The transmetallation of alkali enolates 164 (M = Li, Na, K) with metal salts (M Y L, ) is a general method for the preparation of a large variety of enolates 165, provided that is less electropositive than M. It is particularly suitable for such enolates 165 whose reactivity and/or selectivity is tuned by additional ligands L. Thus, a variety of magnesium, boron, aluminum, siUcon, tin, titanium, zirconium, and zinc enolates become readily available (Scheme 2.48) [2c,d]. Usually, the configuration of the enolates is maintained during the transmetallation, but cis-tmns isomerization in the transmetallated enolates occur occasionally. Individual examples will be discussed with their applications in asymmetric syntheses. 

Miscellaneous Applications. The chemoselective oxidation of alcohols and diols using T 0-i- r)Jt-Butyl Hydroperoxide has been reported. The title reagent has also been employed as a catalyst in Diels-Alder reactions and as an additive in the palladium-catalyzed reaction of aryl-substituted allylic alcohols with zinc enolates of p-dicarbonyl compounds (eq 24). The latter... 

Aldol reactions involving aluminum species are considered to be of less synthetic value because of the ambiguous isomerization of the aldol products, under the influence of the Lewis-acidic aluminum species. Efforts have been made to generate an aluminum enolate in a regiospecific manner. Addition of dialkylchloroalane and zinc to a mixture of an a-halo ketone (126) and an aldehyde leads to the formation of enolate (127), which subsequently reacts with the aldehyde, as shown in Scheme 53.71 This method is applicable to the construction of medium to large rings by intramolecular aldol cyclization of various a-bromocarboxylates of u)-hydroxy aldehydes (e.g. BiCHRC02(CH2) CH0 where — 9, 11 or 12 and R = H or Me). The macrolactonization proceeds in reasonable yield, as shown in Scheme 53. 

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