An enantioselective synthesis of N-methylfucosamine via tandem C-C/C-O bond formation

Article abstract of DOI:10.1021/jo00095a039

Optically pure D-(+)-N-methylfucosamine (8) has been synthesized from a TBDMS-protected methyl L-serinate benzophenone Schiff base (O'Donnell's Schiff base, 1) in seven steps in 13% overall yield. Efficient construction of the requisite amino triol acetate 3a with the proper stereochemical configuration is accomplished in two steps with a chelation-controlled reduction-alkylation reaction using |Bu₂AlH·Al-iBu₃/E-LiCH=CHCH₃, followed by oxidation with OsO₄. Conversion of the Schiff base to the N- benzhydryl protecting group and methylation (Eschweiler-Clark) is accomplished in one pot with NaCNBH₃ in the presence of H₂C=O. Deprotection and oxidation of the primary alcohol, followed by deacetylation with KCN, provided the desired product 8.