Titanium Trichloride Reduction of Substituted N-Hydroxy-2-azetidinones and Other Hydroxamic Acids

Article abstract of DOI:10.1021/jo01291a007

A mild method of reduction of the N-O bond of substituted N-hydroxy-2-azetidinones was required to complete a hydroxamic acid mediated synthesis of substituted β-lactams.Of the several reduction methods studied, most either failed to reduce the N-O bond, cleaved the 2-azetidinone ring, or were inefficient and inconvenient.However, buffered titanium trichloride cleanly reduced the N-O bond of the N-hydroxy-2-azetidinones under conditions compatible with a peripheral acid-sensitive tert-butoxycarbonyl (Boc) group and the base-sensitive chiral center at C₃.These results therefore constitute an efficient synthesis of β-lactams from substituted serinehydroxamic acids.The competitive C-O and N-O reductions of noncyclic hydroxamic acids of various substitution patterns are also described.