DETERMINATION OF THE ABSOLUTE STEREOCHEMISTRY OF CHIRAL AMINES BY H-1-NMR OF ARYLMETHOXYACETIC ACID-AMIDES - THE CONFORMATIONAL MODEL

Molecular Mechanics, semiempirical, and ab initio calculations and DNMR experiments indicate that arylmethoxyacetic acid amides exist in solution as essentially two conformers in equilibrium. Of these conformers, the major one (denominated ap) has the C(alpha)OMe and C=O groups antiperiplanar and the minor one (sp) synperiplanar; the aryl ring is approximately coplanar with the C-alpha-H bond in both conformers. This conformational preference of amides of MPA and other AMAAs is opposite to that of the esters (these prefer the sp conformation) and allows the correlation of the H-1 NMR chemical shifts with the absolute stereochemistry of the amine. On the basis of calculations and experimental results, low polar solvents are recommended for configurational assignment and ee measurement of amines by H-1 NMR of AMAA derivatives.