Asymmetric synthesis of alpha-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 out come 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 c onditions used and b) the electronic properties of the arylidene moiety on the starting imine. High kinetically controlled (2S,R-S) diastereoselectivi ty (-70 degrees C) was achieved for additions of imines bearing relatively electron-rich N-arylidene groups, while an electron-deficient nature of thi s group was found to favor the opposite stereochemical outcome. On the othe r hand, the reactions run under thermodynamically controlled conditions (0 degrees C) afforded equimolar mixtures of the diastereomeric products regar dless of the pattern of substitution on the starting imines. Enantiopure al pha-arylglycinols were readily synthesized by "non-oxidative" Pummerer rear rangement of diastereomerically pure beta-aryl-beta-N-(acyl)aminoalkyl sulf oxides, prepared from the corresponding N-PMP derivatives. (C) 1999 Elsevie r Science Ltd. All rights reserved.