SYNTHESIS AND CIS-DIHYDROXYLATION OF 6H-1,2-OXAZINES - SYNTHESIS OF DIHYDROXYPROLINOLS

An efficient synthesis of 6H-1,2-oxazines 5a-f starting from alpha-hal ogen oximes 2a-f and beta-bromo enol ether 1 is described. Compounds 5 a-d were cis-dihydroxylated with KMnO4 and compound 5e with the NaIO4/ RuCl3 reagent, respectively, to give the diastereomerically pure funct ionalized 1,2-oxazines 7a-e after protection. Intermediate 7a could be transformed into cis-dihydroxylated proline derivatives 8 alpha, 8 be ta which were converted to dihydroxyprolinols 10 alpha and 10 beta or to the N-benzylated compounds 9 alpha and 9 beta. This route constitut es a formal total synthesis of swainsonine 11 since 9 beta is a known intermediate in a published synthesis of this natural mannosidase inhi bitor.