Experimental and computational studies of ring inversion of 1,4-benzodiazepin-2-ones: implications for memory of chirality transformations.
We recently reported the enantioselective syntheses of quaternary 1,4-benzodiazepin-2-ones via memory of chirality. The success of this method depends on formation of conformationally chiral enolates that racemize very slowly under the reaction conditions. As a prelude to undertaking experimental and computational studies on the racemization of these enolates, we have studied the ring-inversion process of the parent 1,4-benzodiazepin-2-ones. In this paper, we use dynamic and 2D-EXSY NMR to characterize inversion barriers. Using DFT calculations, we reproduce the experimental results with high accuracy (within 1-2 kcal/mol). Structural parameters obtained from DFT calculations provide valuable insights into the important effect of the N1 substituent on the ring-inversion barrier and shed light on the mechanism of the memory of chirality method. These measurements and calculations provide a foundation for future studies of benzodiazepine enolates and will be valuable in the design of new memory of chirality reactions.
Lam
Polo C-H
PC
Department of Chemistry, Virginia Tech, Blacksburg, Virginia 24061, USA.
Carlier
Paul R
PR
D001570:Benzodiazepinones / Q000138:chemical synthesis / Q000737:chemistry*; D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism; D013696:Temperature
D001570:Benzodiazepinones