Axial-selective H/D exchange of glycine-derived 1H-benzo[e][1,4]diazepin-2(3H)-ones: kinetic and computational studies of enantiomerization.
Glycine-derived 1H-benzo[e][1,4]diazepin-2(3H)-ones (BZDs) 5d-g featuring C9- and N1- substitution exhibit enantiomerization barriers too high to be measured by (1)H NMR coalescence experiments. To address this problem, we found that room-temperature H/D exchange of these compounds is remarkably selective, affording only the axial-d(1) isotopomers. (1)H NMR spectroscopy was then employed to measure the rate of conformational inversion of these d(1)-compounds at elevated temperatures. These studies reveal the highest enantiomerization barriers (up to 28 kcal/mol) ever determined for a BZD. Density functional theory calculations match the experimental enantiomerization barriers within 1.2 kcal/mol.
Carlier
Paul R
PR
Department of Chemistry, Virginia Tech, Blacksburg, Virginia 24061, USA. pcarlier@vt.edu
Sun
Yang-Sheng
YS
Hsu
Danny C
DC
Chen
Qiao-Hong
QH
D001381:Azepines / Q000737:chemistry*; D005998:Glycine / Q000737:chemistry*; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D013237:Stereoisomerism
C554654:1H-benzo(e)(1,4)diazepin-2(3H)-one; D001381:Azepines; D005998:Glycine