Catalyst-Directed Divergent Catalytic Approaches to Expand Structural and Functional Scaffold Diversity via Metallo-Enolcarbene Intermediates

Catalyst-directed access to divergent products involving three different metals that exclusively form three different products from the same reactants is reported. Each catalyst directs an individual metallo-enolcarbene pathway from enoldiazoacetates and alkenes to a specific product. These include highly selective intermolecular cyclopropanation catalyzed exclusively by dirhodium(II) carboxylates, providing spiro-substituted dihydrooxazoles with greater than 20:1 diastereoselectivity and up to 99% ee; vinylogous addition with subsequent 1,6-proton transfer occurring independently with either Au(I) or Cu(I) catalysis or [3 + 2]-cycloaddition with a Cu(II) catalyst; and direct cycloaddition with the C═N bond of methylenedihydrooxazoles followed by rearrangement forming multiply substituted pyrroles in the presence of a silver catalyst. Allylic aromatization via vinylogous addition selectively delivers aromatic oxazole derivatives from methylenedihydrooxazoles, and when aromatization does not occur by 1,6-proton transfer, [3 + 2]-cycloaddition is the outcome. This catalyst-dependent formation of metallo-enolcarbene intermediates with alkenes demonstrates the tremendous potential of this approach to diversity-oriented-synthesis.