Thioesters aldol reactions, stereoselectivity

Optically active 1,2-diol units are often observed in nature as carbohydrates, macrolides or polyethers, etc. Several excellent asymmetric dihydroxylation reactions of olefins using osmium tetroxide with chiral ligands have been developed to give the optically active 1,2-diol units with high enantioselectivities. However, there still remain some problems, for example, preparation of the optically active anti-1,2-diols and so on. The asymmetric aldol reaction of an enol silyl ether derived from a-benzyloxy thioester with aldehydes was developed in order to introduce two hydroxyl groups simultaneously with stereoselective carbon-carbon bond formation by using the chiral tin(II) Lewis acid. For example, various optically active anti-a,p-dihydroxy thioester derivatives are obtained in good yields with excellent diastereo-... 

Braun, M., Sacha, H. Recent advances in stereoselective aldol reactions of ester and thioester enolates. J. Prakt. Chem. 1993, 335, 653-668. 

Three-component coupling reaction of a-enones, silyl enolates, and aldehydes by successive Mukaiyama-Michael and aldol reactions is a powerful method for stereoselective construction of highly functionahzed molecules valuable as synthetic intermediates of natural compounds [231c]. Kobayashi et al. recently reported the synthesis of y-acyl-d-lactams from ketene silyl thioacetals, a,/l-urisalu-rated thioesters, and imines via successive SbCl5-Sn(OTf)2-catalyzed Mukaiyama-Michael and Sc(OTf)3-catalyzed Mannich-type reactions (Scheme 10.87) [241]. 

The synthesis of the C29-C43 EF segment 479 is summarized in Scheme 68. Methylation of 467 under Prater s conditions stereoselectively afforded 2,3-anti compound 468 (dr = 5-8 1). After TES protection followed by thioester reduction, aldol reaction of the resulting aldehyde with thioketene acetal afforded a-alcohol 469 under Felkin-Anh selectivity. TES deprotection and silver-mediated lactonization followed by TES protection and lactone reduction gave lactol 470. Dehydration, debenzylation, and oxidation furnished aldehyde 471, which was transformed to benzotriazolyl amide 472. 

The BINOL-Ti-catalyzed aldol reaction of chiral P-benzyloxy aldehyde and silyl enol ether provides a facile route to the stereoselective synthesis of both syn and anti-diastereomers of p,S-dihydroxy thioesters, which can be used as the key intermediates for P-lactone synthesis [111] (Scheme 14.39). The high diastereoselectivity of this reaction was found to be dictated by the chirality of the BINOL-Ti catalyst rather than that of the chiral aldehyde substrate. A catalytic enantioselective resolution of secondary alcohol containing silylenol ether moiety has been realized by an aldol reaction catalyzed by BINOL-Ti Lewis acid [112]. 

Because optically active molecules containing 1,2-diol units are often observed in nature (e.g. carbohydrates, macrolides, polyethers), asymmetric aldol reaction of the silyl enolate of a-benzyloxythioacetate 82 with aldehydes has been investigated for simultaneous introduction of two vicinal hydroxy groups with stereoselective carbon-carbon bond-formation. It has, interestingly, been found that the anti-a,fd-dihydroxy thioester derivatives 83 are... 

Subsequently, the same authors synthesized allyl multifunctionalized (Z)-keto allyl halides 241 via the HX4 or TiX4/Bu4NI-mediated vicinal difunctionalization of a,p-unsaturated ketones (at room temperature) " and thioesters (reflux) " with aldehydes in good to excellent yields and complete (Z/ ) stereoselectivity (Scheme 2.141). The formation of halo aldol adducts 242 and 242 was also observed in the case of vinyl ketones when the reaction was conducted at 0°C (Scheme 2.141). ... 

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