Diastereoselectivity of Enolate Anion Protonation. Reaction of HCN with the Enolate of 3-Fluorobutanoic Acid. An ab Initio Molecular Orbital Study

• Published in: Journal of the American Chemical Society Vol. 119; no. 3; pp. 487 - 492
• Main Authors: Rosenberg, Robert E, Mohrig, Jerry R
• Format: Journal Article
• Language: English
• Published: American Chemical Society 22-01-1997
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja962632k

The protonation of the enolate of 3-fluorobutanoic acid by hydrogen cyanide was chosen as a suitable computational model for the H/D exchange reaction of ethyl 3-ethoxybutanoate in ethanol-d. A diastereomeric excess of 82% is found in the experimental system, compared to calculated selectivities which range from 84 to 91%, dependent on the level of theory used. Both cis and trans enolates yield similar diastereomeric ratios. In the lowest energy transition state for each diastereomeric pathway the C−F bond is oriented anti to the incipient C−H bond. These two transition states are differentiated by steric forces, the higher energy diastereomer having a gauche interaction between the CH3 and CO2H groups. The orientation of the C−F bond in these two transition states is rationalized as a stabilizing orbital interaction between the electron rich σ orbital of the enolate−HCN bond and the low-lying σ* orbital of the C−F bond, an interaction also proposed by Anh to explain the selectivity of nucleophilic addition to chiral carbonyl compounds. Alternatively, an electrostatic argument can account for the data. When the C−F bond is anti to the incipient C−H bond, the dipole moment, and hence the electrostatic energy, is at a minimum.