Rh(III)-Catalyzed, <i>N</i> -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 groups as the origin of reactivity for the projection and development of forward conversion reactivity modalities. This forward reactivity exploration synthetic practice has allowed for the productive discovery of reactivity step sequences that emerge from the functional group of interest. Herein, we report both forward reactivity exploration and backward reactivity exploration as expansive synthetic practices for the comprehensive projection and development of both forward conversion reactivity and backward conversion reactivity. The backward reactivity exploration synthetic practice provides an inclusive avenue for the revelation of reactivity step sequences progressing in 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 the benzodiazepine skeleton and the backward generation of the indazole skeleton, respectively.