Reduction preparation, directed aldol reaction

In anticipation of the final carbon-carbon bond construction that is required to prepare the intact seco acid of erythronolide B using a directed aldol reaction to form the C(10)-C(l 1) bond, it was first necessary to prepare the requisite chiral aldehyde 80. Although the synthesis of 80 had been previously reported, we elected to devise an alternative route to access this material that commenced with the addition of the chiral boron enolate 37 0 to propionaldehyde to furnish 81 (Scheme 12). The sequential protection of the secondary hydroxyl group and removal of the chiral auxiliary gave 82, which was then converted to 80 by over-reduction followed by reoxidation under Swem conditions. 

As practiced in the preceding syntheses by Evans and Nishiyama and Yamamura, the A-ring fragment 43 is formed through substrate-directed vinylogous aldol reaction of the Brassard-type diene 19 and the chiral aldehyde 42, which is prepared using Brown s protocols for enantioselective allylation [53], followed by hydroxy-directed nnn-diastereoselective reduction of the C3 ketone (Me4NB(OAc)3H) [41],... 

For the preparation of 1,2-diketones the coupling of acyl cyanides is a direct method. Enones undergo reductive dimerization at the P-position which is followed by an aldol reaction in sterically favorable cases.Benzylideneimines give mainly syn-1,2-diamines in the reductive coupling which is also accelerated by Yb(OTf)3. 

Chiral a-sulfinyl dimethylhydrazones form stabilized carbanions that can be used in enantioselective aldol reactions. A typical example is shown in equation (21). Removal of the chiral sulfur auxiliary is accomplished by reductive desulfurization. Under these conditions recovery and reuse of the sulfur moiety is impossible. Synthetic and optical yields reported for these aldol reactions are modest in most cases. However, in a direct comparison to the SAMpMaMP methodology, Annunziata has prepared (-)-(/ )-[6]-gingerol in 60% finders prior synthesis had yielded this aldol product in 36% ee. ... 

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