Asymmetric synthesis of N,O-diprotected (2S,3S)-N-methyl-delta-hydroxyisoleucine, noncoded amino acid of halipeptin A

The first enantioselective synthesis of N,O-diprotected (2S,3S)-N-methyl-delta-hydroxyisoleucine 4, starting from readily available (tert-butyldimethylsilyl)-2-butyn-1-ol 5, is described. The key steps of this stereochemical flexible synthetic route involve a silyl-assisted [3,3]-sigmatropic rearrangement, for the establishment of the correct stereoisomeric pattern, and a triethylsilane–TFA induced reduction of an oxazolidinone intermediate, to yield the requested N-methylation.