Hydrophobic vitamin B₁₂. Part 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-methoxy-2-phenylpropionate was carried out at -1.8V vs. SCE in N,N-dimethylformamide, as mediated by a simple hydrophobic vitamin B₁₂, [Cob(II)7C₃ester]ClO₄, and a strapped hydrophobic vitamin B₁₂, [Cob(II)(c,10-PDA)6C₃ester]ClO₄, to afford ethyl 2-methoxy-2-phenylpropionate and ethyl 2-methoxy-3-phenylpropionate in the dark. The simple hydrophobic vitamin B₁₂ acted to afford ethyl (S)-2-methoxy-2-phenylpropionate, the hydrogen-substituted product, in 55% e.e., while the strapped hydrophobic vitamin B₁₂ was in favor of formation of the corresponding R enantiomer in 26% e.e. Since the reaction proceeds via formation of an intermediate in which the ethyl 2-methoxy-2-phenylpropionate moiety is bound to the hydrophobic vitamin B₁₂, the chiral microenvironment provided by the peripheral groups placed around the corrin framework is responsible for the enantioselective formation of the alkylated hydrophobic vitamin B₁₂. The enantioselective coordination of the substrate species was rationalized by means of molecular mechanics and dynamics computations as well as by Monte Carlo conformational search; the simple hydrophobic vitamin B₁₂ with the S substrate is lower in energy than the complex with the R substrate by l.8 kJ mol^-1, while the strapped hydrophobic vitamin B₁₂ with the R substrate is lower than the identical complex with the S substrate by 2.0 kJ mol^-1.