A Mechanistic and Structural Investigation of the (−)-Sparteine Mediated Asymmetric Benzylic Lithiation Substitution Reactions of <i>N</i>-Boc-<i>N</i>-(<i>p</i>-methoxyphenyl)benzylamine

Abstract

Mechanistic and structural studies show the high enantioenrichments in the products from lithiation−substitutions of N-Boc-N-(p-methoxyphenyl)benzylamine (1) by n-BuLi/(−)-sparteine (6) arise from an enantioselective deprotonation of 1 to provide configurationally stable (R)-2/6. NMR spectroscopy establishes that 13C, 6Li labeled (R)-2/6 and (S)-2/6 are monomeric with lithium complexed to the benzylic position, the carbonyl of the Boc group and (−)-sparteine. Deprotonations of the tertiary protons in (R)- and (S)-N-Boc-N-(p-methoxyphenyl)-α-methylbenzylamine ((R)-8 and (S)-8) with n-BuLi/TMEDA provide (R)-9/TMEDA and (S)-9/TMEDA, respectively, with high enantioenrichments. Absolute configurations assigned to (R)-2 and (R)-1-d1 allow analysis of the electrophile dependent stereochemistry of the reactions of these configurationally stable organolithium intermediates.