ASYMMETRIC STRECKER SYNTHESIS OF THE 4 ALPHA-QUATERNARY 1-AMINO-2-METHYLCYCLOHEXANECARBOXYLIC ACIDS

The synthesis of the four 1-amino-2-methylcyclohexanecarboxylic acids 13, 14, 15, and 16 from diastereomeric mixtures of the a-amino nitrile s 1-4 by successive application of cone. H2SO4, Pd/C H-2, and cone. HC l is described. The amino nitriles 1-4 were prepared by asymmetric Str ecker synthesis under various reaction conditions. The formation of 1- 4 is thermodynamically controlled in protic solvents (e.g. MeOH), wher eas the reaction is under kinetic control in non-protic solvents (e.g. hexane). The separation of the alpha-amino amides 5-8, which were obt ained by partial hydrolysis of 1-4, was achieved by CC, LPLC, and HPLC . The absolute configuration of all synthesized compounds was determin ed by means of only two X-ray analyses with consecutive correlations. The steric control of the asymmetric Strecker synthesis is discussed.