Asymmetric Synthesis of -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 snifoxide 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, Rs) 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 re, actions run under thermodynamically controlled conditions (0 °C) afforded equimolar mixtures of the diastereomeric products regardless of the pattern of substitution on the starting imines. Enantiollmre cLarylglycinols were readily synthesized by "non-oxidative" Pummerer rearrangement of diastereomerically pure [~-atyl-13-N-(acyl)aminoalkysl ulfoxides, prepared from the corresponding N-PMP derivatives