Experimental and computational studies of ring inversion of 1,4-benzodiazepin-2-ones: implications for memory of chirality transformations |
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Authors: | Lam Polo C-H Carlier Paul R |
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Institution: | Department of Chemistry, Virginia Tech, Blacksburg, Virginia 24061, USA. |
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Abstract: | 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. |
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