Absolute configurations of chiral herbicides determined from vibrational circular dichroism

Enantiopure herbicides (+)‐2‐(4‐chloro‐2‐methylphenoxy) propanoic acid, (+)‐ 1 and (+)‐2‐(2,4‐dichlorophenoxy) propanoic acid, (+)‐ 2 were investigated using vibrational circular dichroism (VCD). Experimental absorption and VCD spectra of (+)‐ 1 and (+)‐ 2 in CDCl 3 solution in the 2000–900 cm −1 region were compared with the ab initio predictions of absorption and VCD spectra obtained with density functional theory using the B3LYP/6‐31G* basis set for different conformers of ( R )‐ 1 and ( R )‐ 2. Due to the intermolecular hydrogen bonding, this comparison did not provide unambiguous conclusions. To eliminate intermolecular hydrogen bonding influence, the two acids 1 and 2 were converted to the corresponding methyl esters, namely, (+)‐methyl 2‐(4‐chloro‐2‐methylphenoxy) propanoate, (+)‐ 3 and (+)‐methyl 2‐(2,4‐dichlorophenoxy) propanoate, (+)‐ 4. The experimental VCD spectra were measured for these esters and ab initio calculations for different conformers of ( R )‐ 3 and ( R )‐ 4 were carried out. The experimental VCD spectra and corresponding population‐weighted theoretical VCD spectra were found to be in excellent agreement, which allowed unambiguous determination of absolute configuration of 3 and 4 as (+)‐( R ). Since esterification does not invert the configuration, the absolute configuration of the parent acids 1 and 2 is the same as that of corresponding methyl esters. Chirality 17:S1–S8, 2005. © 2004 Wiley‐Liss, Inc.