Benzyl ester, enantioselective excess

The synthetic applicability is somewhat limited in that the asymmetric induction is very substrate dependent. Esters other than benzyl esters showed lower enantiomeric excesses. The substitution pattern at the 7 position has a drastic effect on the efficiency of the asymmetric induction. Monosubstitution led to enantioselectivities around 35% ee (with inductor 19, — 40°C). In the case of unsubstituted 7 position, the induction went down to 10% ee [39]. For lactones, enantioselectivities up to 43% ee were reported (inductor 20, — 55°C) [40]. 

The asymmetric benzylation of 16 was promoted by phosphonium salt 12 in moderate yield with encouraging levels of enantioselectivity when the catalyst loading was as low as 0.20 mol % (Table 7.1, entry 3). Further, a low temperature improved the enantiomeric excess to 50% ee (entry 5). A low enantiomeric excess obtained using the phosphonium salt 13 (entry 6) suggested a critical role for two mandelamide units in the catalytic efficiency of phosphonium salt 12. Unfortunately, this reaction proved to be highly substrate-sensitive, and other alkylating agents or different ester substituents in 16 afforded low enantioselectivities. 

The addition reaction of fert-butyl thioacetate-derived silyl ketene acetal produces the corresponding aldol adducts in 84% yield and up to 96% enantiomeric excess (Eq. 16). The enantioselectivity of the products was observed to be optimal with toluene as solvent the use of the more polar dichloromethane consistently produced adducts with 10-15% lower enantiomeric excess. The bulkier ferf-butylthioacetate-derived enol silane was found to lead to uniformly higher levels of enantioselectivity than the smaller S-ethyl thioketene acetal. This process is impressive in that it tolerates a wide range of aldehyde substrates for instance, the aldol addition reaction has been successfully conducted with aldehydes substituted with polar functionaUty such as N-Boc amides, chlorides, esters, and 0-benzyl ethers. A key feature of this system when compared to previously reported processes was the abiUty to achieve high levels of stereoselectivity at 0 °C, in contrast to other processes that commonly prescribe operating temperatures of -78 °C. 

In contrast to the diastereoselectivity of the reaction with benzyloxyacetaldehyde derivatives, the Sc(III)-(5, 5)-PyBOX-catalyzed cycloadditions of 2-benzopyrylium-4-olate with methyl and benzyl pyruvate showed high exoselectivity (Scheme 7.26 and Table 7.20). This is probably attributed to the unfavorable dipolar interactions between the carbonyl groups of 2-benzopyrylium-4-olate and the ester in the eniio-approach. However, the maximum enantiomeric excess of the exo-adduct was only 56% ee when (S,S)-PyBOX-TPSm was used as a ligand (Figure 7.3 and Table 7.20, entry 3). After several attempts to increase the enantioselectivity, both diastereo- (up to exo endo = 96 4) and enantioselectivities (up to 87% ee (exo)) were determined to improve in the Sc(III)-(5,5)-PyBOX-i-Pr-catalyzed reaction (up to 94% yield) when pyruvic acid was used as an additive (entries 5, 6, 8, and 9). By the examinations of some... 

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