Highly Selective Stereodivergent Synthesis of Separable Amide Rotamers, by Using Pd Chemistry, and Their Thermodynamic Behavior

Abstract

By using Pd chemistry, a highly selective stereodivergent synthesis of separable amide rotamers was achieved. Allylation of 2,4,6-tri-tert-butylanilides using a pi-allyl-Pd catalyst gave N-allylated anilides with moderate-to-excellent Z-rotamer selectivity (Z/E = 3 to > 50). The Z-rotamer selectivity depends considerably on the substituent on the anilide substrates. On the other hand, the E rotamers of N-allylated 2,4,6-tri-tert-butylanilides were obtained with almost complete selectivity (E/Z > 50) through O-allylation of 2,4,6-tri-tert-butylanilides and the subsequent Pd(II)-catalyzed Claisen rearrangement of the resulting O-allyl imidate. The prepared anilide rotamers changed to equilibrium mixtures in which the E rotamer was the major isomer when heated in toluene.