HYDROPHOBIC VITAMIN-B12 .13. ASYMMETRIC REACTION OF HYDROPHOBIC VITAMIN-B12 UNDER ELECTROCHEMICAL CONDITIONS AND RATIONALIZATION OF ENANTIOSELECTIVITY BASED ON CONFORMATIONAL-ANALYSIS

The controlled-potential electrolysis of racemic ethyl 3-bromo-2-metho xy-2-phenylpropionate was carried out at -1.8 V vs. SCE in N,N-dimethy lformamide, as mediated by a simple hydrophobic vitamin B12, [Cob(II)7 C3ester]ClO4, and a strapped hydrophobic vitamin B-12, [Cob(II)(c,10-P DA)6C3ester]ClO4, to afford ethyl 2-methoxy-2-phenylpropionate and eth yl 2-methoxy-3-phenylpropionate in the dark. The simple hydrophobic vi tamin B-12 acted to afford ethyl (S)-2-methoxy-2-phenylpropionate, the hydrogen-substituted product, in 55% e.e., while the strapped hydroph obic vitamin B12 was in favor of formation of the corresponding R enan tiomer in 26% e.e. Since the reaction proceeds via formation of an int ermediate in which the ethyl 2-methoxy-2-phenylpropionate moiety is bo und to the hydrophobic vitamin B-12, the chiral microenvironment provi ded by the peripheral groups placed around the corrin framework is res ponsible for the enantioselective formation of the alkylated hydrophob ic vitamin B12. The enantioselective coordination of the substrate spe cies was rationalized by means of molecular mechanics and dynamics com putations as well as by Monte Carlo conformational search; the simple hydrophobic vitamin B12 with the S substrate is lower in energy than t he complex with the R substrate by 1.8 kJ mol-1, while the strapped hy drophobic vitamin B12 with the R substrate is lower than the identical complex with the S substrate by 2.0 kJ mol-1.