Rh(III)-Catalyzed, N-Amino-Directed C-H Coupling with 2-Oxo-3-Butynoates to Benzodiazepines

The current state of the art organic synthesis wisdom is centered on functional group as the origin of reactivity for the projection and development of forward conversion reactivity modality. This forward reactivity exploration synthetic practice has allowed for the productive discovery of reactivity step sequence emerged from the functional group of interest. Herein, we report both forward reactivity exploration and backward reactivity exploration as the expansive synthetic practice for the comprehensive projection and development of both forward conversion reactivity and backward conversion reactivity modality. The backward reactivity exploration synthetic practice provides an inclusive avenue for the revelation of reactivity step sequence progressing in the reverse order with respect to the forward construction reactivity modality for the creation of the functional group of interest. The alkyne functional group in the form of 2-oxo-3-butynoate (ester) has been diversified into an alkene group in the forward conversion and an imine group (one fragment via alkyne bond cleavage) in the backward conversion through Rh(III)-catalyzed, N-amino-directed C-H coupling. The forward conversion reactivity and backward conversion reactivity have empowered the forward generation of benzodiazepine skeleton and backward generation of indazole skeleton, respectively. The synthetic versatility exemplified herein promises forward reactivity exploration and backward reactivity exploration as an important conceptual foundation for unified synthetic practice.