28. Mechanism of trifluoroacetic-acid-promoted N-to-S acyl transfer of enamides

Jiang, Y.-Y.;* Zhu, L.; Man, X.; Liang, Y.; Bi, S.* Tetrahydron 2017, 73, 4380–4386. Download Link

Abstract: An enamide-based 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase peptide synthesis (SPPS) method was recently disclosed for the synthesis of peptide thioesters. In this manuscript, density functional theory (DFT) calculations were performed to provide deeper mechanistic insights into this reaction. The calculation results clarified the detailed mechanisms of the relevant N-to-S acyl transfer and hydrolysis, the overall rate-determining step, the role of trifluoroacetic acid (TFA), as well as the influence of the stereo-configuration of amide bond and C]C bond on reaction rate.