33 SYNTHESIS OF 6-DEOXYERYTHRONOLIDE B
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A stereoselective, directed aldol condensation to construct erythro (2,3-syn)-and threo (2,3-anti)-β-hydroxy-α-methyl carbonyl systems has been achieved via Z- or E- boron enolate. E-enolate of 12 and Z-enolate of 13 generated stereoselectively by a combination of 14 and diisopropylethylamine reacted with aldehydes to afford erythro aldols exclusively. On the other hand, Z-enolate of 15 and E-enolate of 13 prepared by 16 and the same amine gave rise to threo-aldols selectively. Thus, a 2,3-stereochemical problem has been solved, while the complete control of 3,4-stereochemistry regarding Cram rule has not been realized yet. This new methodology was applied to a synthesis of 6-deoxyerythronolide B (2). The four aldol condensations using boron enolates constituted crucial C-C bond forming steps, including simplified synthesis of Prelog-Djerassi lactone (28). The Cu(I)-mediated thiol ester activation brought about lactone ring formation, which completed the synthesis of 2. The total number of steps used to create 10 chiral centers is impressively small as compared with those required in recent syntheses of macrolides of a similar type and complexity.
