Asymmetric synthesis of α-arylglycinols via additions of lithium methyl p-tolyl sulfoxide to N-(PMP)arylaldimines followed by 'non oxidative' Pummerer reaction

Article abstract of DOI:10.1016/S0040-4020(99)00064-2

The results presented in this paper demonstrate that the stereochemical outcome of the reversible additions of lithium (R)-methyl p-tolyl sulfoxide to N-arylidene-p-anisidines (N-PMP imines) is a function of a) the reaction conditions used and b) the electronic properties of the arylidene moiety on the starting imine. High kinetically controlled (2S,R(S)) diastereoselectivity (-70 °C) was achieved for additions of imines bearing relatively electron-rich N-arylidene groups, while an electron-deficient nature of this group was found to favor the opposite stereochemical outcome. On the other hand, the reactions run under thermodynamically controlled conditions (0 °C) afforded equimolar mixtures of the diastereomeric products regardless of the pattern of substitution on the starting imines. Enantiopure α-arylglycinols were readily synthesized by 'non-oxidative' Pummerer rearrangement of diastereomerically pure β-aryl-β-N-(acyl)aminoalkyl sulfoxides, prepared from the corresponding N-PMP derivatives.