ALPHA-D-MANNOPYRANOSYL)OXY]ALLYL]-TRIBUTYLSTANNANE - A NEW CHIRAL REAGENT FOR THE ASYMMETRIC ALPHA-HYDROXYALLYLATION OF ALDEHYDES

Reactions of -alpha-D-mannopyranosyl)oxy]allyl]tributylstannane (6) wi th several chiral and achiral aldehydes are described. This reagent wa s designed in anticipation that significant diastereofacial bias in re actions with aldehydes would be exerted by the mannosyl auxiliary as a consequence of the exo anomeric effect. In fact, chiral reagent 6 dis plays especially useful diastereoselectivity in BF3.OEt(2)-promoted ma tched double asymmetric reactions with chiral aldehydes (S)-7 (18:1 se lectivity), (R)-19 (greater than or equal to 20:1 selectivity), and (R )-26 (greater than or equal to 20:1 selectivity). Reagent 6 also gives good to excellent selectivity in mismatched double asymmetric reactio ns with (R)-7 (16:1 selectivity), (S)-19 (5:1 selectivity), (S)-20 (7: 1 selectivity), but with (S)-26 the mismatched double diastereoselecti vity falls to 2:1. Reagent 6 also participates in MgBr2-promoted react ions with alpha-alkoxy aldehydes (e.g., 19), although it proved incapa ble of overriding th intrinsic diastereofacial bias of the MgBr2-compl exed aldehyde. In all cases, it appears that the aldehyde-Lewis acid c omplexes approach the allylstannane unit of 6 on the side opposite to the pyran C-O bond with the vinyl ether C-O bond oriented anti to the pyranoside C(1)-C(2) bond, as dictated by the exo anomeric effect. How ever, reactions of 6 with alpha-(benzyloxy)acetaldehyde (45) demonstra te that the enantioselectivity of the reagent is attenuated by the ten dency of reactions to occur via transition states with the enol ether either in the s-trans (e.g., 53, 56) or the less stable s-cis rotamer (e.g., 54, 57), which exhibit opposite enantiofacial selectivities. It is suggested that double asymmetric reactions involving 6 display syn thetically useful levels of enantioselectivity because the chiral alde hydes are able to discriminate between the s-cis/s-trans rotamer pool such that the matched pair double asymmetric reactions proceed almost exclusively via transition states with s-trans enol ether rotamers. Pa thways involving s-cis enol ether rotamers (cf., 32, 43) become signif icant in mismatched double asymmetric reactions of aldehydes with very large intrinsic diastereofacial preferences, as in the reactions of 6 with (S)-26-BF3.Et(2)O and (R)-19-MgBr2.