A general approach to enantiomerically pure methylcarbinols. Asymmetric synthesis of antibiotic (-)-A26771B and the WCR sex pheromone

Article abstract of DOI:10.1021/jo00079a024

Either (R) or (S) enantiomerically pure methylcarbinol groups are conveniently produced from monosubstituted alkenes via the Sharpless asymmetric dihydroxylation (AD) reaction. The initial AD product, 1,2- dihydroxyalkane, obtained with predictable absolute configuration and high enantiomeric purity, is converted into 2-acetoxy-1-bromoalkane and then subjected to reductive debromination. These conditions are compatible with a variety of functional groups, including acetal, ester, nitrile, ketone, and silyl ether. The advantages of this method are demonstrated by highly efficient, asymmetric syntheses of enantiomerically pure natural products. All four stereoisomers of the WCR sex pheromone 4 are prepared in six steps form nona-1,8-diene in 10-15% overall yield. Similarly, a highly efficient formal total synthesis of antibiotic (-)-A26771B (5) is accomplished via two alternative approaches. The first one transforms dodec-11-enal into enantiomerically pure 5 in 11 steps and 4.1% overall yield, while the second achieves the same transformation in 12 steps and 6.6% overall yield.