Electrophiles bearing chiral auxiliaries

Under Lewis add catalysis, the reaction of allylsilanes takes place easily with a-enones but not with a,P-unsaturated esters [162]. Because disappointing results were obtained in reactions of allylmetals with a,P-unsaturated carbonyl compounds, reactions of allylsilanes with electrophiles bearing chiral auxiliaries have been examined. Schultz and Lee [1435] performed the T1CI4 catalyzed addition of trimethylallylsilane to compound 7.67 at -78°C. After treatment with methylhy-droxylamine in acidic media, the 1,4-adduct 7.80 was obtained with high ee (Figure 7.56). Under similar conditions, N-enoyloxazolidinone 7.68 (R = Ph) or sultam... 

In the late 1980s various asymmetric procedures for the synthesis a-hydrazino acids, based on the electrophilic amination of an enolate bearing a chiral auxiliary by a dialkylazodi-carboxylate, have appeared in the literature (Table 1)J55 68 72i The a-hydrazino acid is recovered in high yield after cleavage of the chiral auxiliary and acidolysis of the Boc groups in 63. The D-enantiomer is obtained with 65, A and the L-enantiomer with 66,[551 67,169 71 and 68.[70] A chiral auxiliary is not required for hydrazinating chiral (i-hydroxyesters.172 ... 

Thiazolidinethiones constitute a class of versatile chiral auxiliaries for asymmetric synthesis. Their easy preparation from readily available /3-amino alcohols and the high levels of asymmetric induction they provide make them excellent chiral auxiliaries for the preparation of chiral intermediates in the synthesis of natural products. These chiral auxiliaries have been utilized in a wide variety of synthetic transformations such as asymmetric aldol-type acyloin condensation, stereoselective alkylation of different electrophiles (Stetter reaction), and stereoselective differentiation of enantiotopic groups in molecules bearing prochiral centers <2002COR303>. 

The degree of asymmetric induction for a substrate bearing a remote chiral auxiliary is discussed in the next example. Palladium(0)-catalyzed asymmetric allylation of (S)-proline allyl ester amides gives the (S.-SJ-diastereomer with d.r. 93 7s7. If the electrophile is not attached to the proline moiety but added as allyl acetate, the diastereoselectivity is only moderate (d.r. 65.5 34.5-74 26 for the methyl or ethyl proline esters). At 0 =C, the reaction does not yield the expected products and at higher temperatures (40 C), only d.r. 82.5 17.5 is obtained. The alkylation with j cr-butyllithium and allyl iodide at — 78 =C gives the epimeric (7 )-enantiomer with d.r. 88.5 11.5. 

The bulk of this chapter is concerned with second-generation methods, subdivided according to whether the reactant bearing the chiral auxiliary reacts as a nucleophile, an electrophile, or neither. We begin, however, by considering a few examples of non-stereodifferentiating and first-generation methods. 

The second-generation methods described in this chapter have been divided into three main groups. In the first, which t e up the rest of this section, the substrate bearing the chiral auxiliary reacts as a nucleophile, in the second (section 5.4) it is electrophilic, and in the third (section 5.5) it is neither. 

Alternatively, alkoxycarbene complexes are formed upon alcoholysis of strongly electrophilic acyloxycarbene complexes 16 [26] generated by in situ acylation of tetraalkylammo-nium acyl metalates 15. These compounds are obtained from lithium precursors 11 and can be stored in a refrigerator for months. This is the method of choice for the synthesis of chiral metal carbenes 17 bearing terpene or sugar auxiliaries (Scheme 9). 

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