A formal [3,3]-sigmatropic rearrangement route to quaternary α-vinyl amino acids:: Use of allylic N-PMP trifluoroacetimidates

Pd(II)-mediated rearrangement of allylic N-PMP (p-methoxyphenyl) trifluoroacetimidates provides the first formal sigmatropic route to quaternary, alpha-vinylic amino acids, potential suicide substrates for PLP enzymes. The amino acid side chains enter via transition-metal-mediated C-C bond constructions, including (1) Cu(l)-mediated conjugate addition (Ala); (ii) Pd(O)/AsPh3-mediated Stille coupling (allyl-Gly, Phe, DOPA, rn-Tyr); and (iii) Pd(O)/Pt-BU3-mediated Negishi coupling (Leu). In the synthesis of the DOPA decarboxylase inactivator, a-vinyl-m-tyrosine, the new N-PMP trifluoroacetimiclate rearranges much more efficiently than the corresponding trichloroacetimidate.