Asymmetric Synthesis of the Nonproteinogenic Silicon-Containing α-Amino Acids (R)- and (S)-α-[(Trimethylsilyl)methyl]alanine

The nonproteinogenic silicon-containing, alpha,alpha-disubstituted alpha-amino acids (R)- and (S)-2-amino-2-methyl-3-(trimethylsilyl)propanoic acid [(R)- and (S)-alpha-[(trimethylsilyl)methyl]alanine, (R)-1 and (S)-1] were synthesized by multistep syntheses, starting from diethyl malonate, and both were isolated with an enantiomeric purity of > 99% ee. Compound rac-1 was also prepared. The key step of the asymmetric syntheses of (R)-1 and (S)-1 was all enantioselective enzyme-catalyzed (porcine liver esterase) ester cleavage of the prochiral substrate diethyl methyl[(trimethylsilyl)methyl]malonate. The absolute configurations of (R)-1 and (S)-1 were established by crystal structure analyses of (R)-1 and of its rhodium complex (S-Rh,R-C)-16.