1H NMR spectroscopic criteria for the configuration of N-acyl-alpha,beta-dehydro-alpha-amino acid esters.

The diagnostic values of the following three spectral criteria for the configuration of N-acyl-alpha,beta-dehydro-alpha-amino acid esters were examined: (i) the proton at the beta-position at the double bond of a Z-isomer is shielded if compared with the respective E-isomer (delta(beta)Z < delta(beta)E); (ii) the proton at the nitrogen atom is shielded in a Z-isomer in comparison with the corresponding E-isomer (delta(NH)Z < delta(NH)E); and (iii) changing of the solvent from CDCl3 to deuterated trifluoroacetic acid (TFA) causes shielding of the H(beta) vinylic proton of an E-isomer or deshielding of the respective proton of the Z-isomer (delta(CDCl3)E > delta(TFA)E or delta(CDCl3)Z < delta(TFA)Z). The investigations were based on a set of 22 (Z)- and (E)-N-acyl-alpha,beta-dehydro-alpha-amino acid esters of diverse structures, with aliphatic, aromatic and heteroaromatic substituents at the vinylic beta-carbon; most of the examined compounds were hitherto unknown. The application of the substituent effect additivity rule given by Pascual et al. for olefinic protons leads to evidently erroneous configuration assignments of N-acyl-alpha,beta-dehydro-alpha-amino acid esters. The considered criteria were fulfilled for all the examined cases with one exception [the second criterion for the alpha-pivaloylamino-beta-(2-furyl)acrylates]. The comparison of changes in the chemical shifts of H(beta) vinylic protons in CDCl3 and deuterated TFA seems to be the most reliable and useful configuration criterion, as it can be used in the case of a single isomer. Copyright 2004 John Wiley & Sons, Ltd.