Regiochemistry‐Directed Syntheses of Polyhydroxylated Alkaloids from Chiral Aziridines

In this study, two possible regiochemical pathways of aziridine ring opening, termed “regiochemistry-directed branches for 2-substituted aziridines” are described, providing easy access to two classes of compound from a common synthetic intermediate. Application of this synthetic strategy, with stereoselective dihydroxylation and reductive amination as the key steps, allowed the asymmetric synthesis of natural and unnatural polyhydroxylated alkaloids including the calyculin fragment C33–C37, 1,4-dideoxy-1,4-imino-l-ribitol and analogues of hyacinthacine, swainsonine, castanospermine, and deoxynojirimycin. The initial domino reactions consisted of aziridine ring opening and debenzylation, and reductive double annulations were established for the preparation of bicyclic pyrrolizidine and indolizidine—represented by 8-deoxyhyacinthacine and (3R)-methyl-8-deoxyswainsonine—with remarkable stereoselectivity and in high yield.