Strategy for Enantio- and Diastereoselective Syntheses of All Possible Stereoisomers of 1,3-Polyol Arrays Based on a Highly Catalyst-Controlled Epoxidation of α,β-Unsaturated Morpholinyl Amides: Application to Natural Product Synthesis

We describe a new strategy for enantio- and diastereoselective syntheses of all possible stereoisomers of 1,3-polyol arrays. This strategy relies on a highly catalyst-controlled epoxidation of α,β-unsaturated morpholinyl amides promoted by the Sm-BINOL-Ph₃As=O (1:1:1) complex, followed by a conversion of morpholinyl amides into ketones and diastereoselective ketone reduction. Highly enantio- (up to >99% ee) or diastereoselective (up to >99.5:0.5) epoxidation was achieved using 5-10 mol% of the Sm complex to afford synthetically very useful, nearly optically pure α,β-epoxy morpholinyl amides. Stereoselectivity of the epoxidation was controlled by the chirality of BINOL with overwhelming inherent diastereofacial preference for the substrate. Combination with the syn- and anti-selective ketone reduction with the highly catalyst-controlled epoxidation allowed for an iterative strategy for the syntheses of all possible stereoisomers of 1,3-polyol arrays. Eight possible stereoisomers of 1,3,5,7-tetraol arrays were synthesized with high to excellent stereoselectivity. Moreover, the efficiency of the present strategy was successfully demonstrated by enantioselective syntheses of several 1,3-polyol/α-pyrone natural products, for example, cryptocaryolone diacetate.