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

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 degrees 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 degrees C) afforded equimolar mixtures of the diastereomeric products regardless of the pattern of substitution on the starting imines. Enantiopure alpha-arylglycinols were readily synthesized by "non-oxidative" Pummerer rearrangement of diastereomerically pure beta-aryl-beta-N-(acyl)aminoalkyl sulfoxides, prepared from the corresponding N-PMP derivatives. (C) 1999 Elsevier Science Ltd. All rights reserved.