Temperature- and Electrophile-Dependent Stereocontrol: A Structural and Mechanistic Investigation of (−)-Sparteine-Mediated Asymmetric Lithiation−Substitution Sequences of <i>N</i>-Boc-<i>N</i>-(<i>p</i>-Methoxyphenyl)cinnamylamine

Abstract

The reaction pathways for the highly enantioselective, (−)-sparteine-mediated, lithiation−substitution reactions of N-Boc-N-(p-methoxyphenyl)cinnamylamine ((E)-2) have been investigated. The solution structure of the major allyllithium intermediate has been determined by 6Li and 13C NMR to be a monomeric η3 species, endo-syn-anti-8·1. The complexes exo-syn-anti-8·1, endo-syn-syn-8·1, and exo-syn-syn-8·1 are also shown to be present in solution. The enantiodetermining step in the lithiation−silylation or lithiation−alkylation of (E)-2 can involve asymmetric deprotonation, dynamic kinetic resolution, or dynamic thermodynamic resolution. The results reported herein establish that each of these pathways can be operative. This information allows determination of the stereochemical course for each step of these reactions and permits preparation of either epimer at the new stereogenic carbon.