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

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 13 C, 6 Li 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 - d 1 allow analysis of the electrophile dependent stereochemistry of the reactions of these configurationally stable organolithium intermediates.