Stereocontrolled asymmetric total synthesis of protomycinolide IV (1) was achieved, based on the organoaluminum-promoted stereospecific pinacol-type 1, 2-rearrangement. Two chiral fragments, C (l)-C (9) and C (11)—C (17) portions, were constructed from a common chiral starting material,(S)-ethyl lactate. High diastereoselectivity of the nucleophilic attack on the Me3Si-bearing a-methyl-d, 7-unsaturated carbonyl compounds was fully utilized for establishing the chiral centers at C (5) and C (6) relativeto C (4j and C (15) relative to C (14). For the stereocontrol of the Me substituentat C (8), two methods were newly devised:(i) thermodynamic equilibration of-lactone 16 and (ii) acid-catalyzed stereoselective cyclization of ketene dithioacetal possessing an internal hydroxyl group.

Recent interest in the total synthesis of macrolide or ionophore antibiotics invoked rapid progress of the stereoregulating method for the synthesis of acyclic molecules. 1 In this conjunction, a number of efficient methods have been recently devised, 23 such as the stereoselective aldol condensation213 etc., which serve well for the control of the acyclic stereochemistry, bothin enantio-and diastereomerical senses. However, there is room for further de-velopment, seeking generality and flexibility against structural diversity. Our recent investigation in this area revealed a viable approach based on 1, 2-rearrangement in acyclic systems, which proved to be highly efficient in light of its excellentenantiospe-cificity.