Borane-Catalyzed Stereoselective C–H Insertion, Cyclopropanation, and Ring-Opening Reactions

Abstract

Lewis acidic boranes have been shown to be effective metal-free catalysts for highly selective reactions of donor-acceptor diazo compounds to a range of substrates. The reactions of α-aryl α-diazoesters with nitrogen heterocycles indole or pyrrole selectively generate C3 and C2 C–H insertion products, respectively, in good to excellent yields even when using unprotected indoles. Alternatively, benzofuran, indene, and alkene substrates give exclusively cyclopropanated products with α-aryl α-diazoesters, whereas the reactions with furans lead to ring-opening. Comprehensive theoretical calculations have been used to explain the differing reactivities and high selectivities of these reactions. Overall, this work demonstrates the selective metal-free catalytic reactions of α-aryl α-diazoesters with (hetero)cycles and alkenes. This simple, mild reaction protocol represents an alternative to the commonly used precious metal systems and may provide future applications in the generation of biologically active compounds. Efficient and facile routes to heterocyclic compounds are highly desirable because of their remarkable biological importance and applications in drugs approved by the Food and Drug Administration. Current synthetic routes frequently use precious metal-catalyzed reactions. The problems associated with the limited resources of precious metals as well as their toxicities can be avoided through metal-free approaches. Our investigations on the reactivities of diazoesters toward the (hetero)arenes reveal that by using Lewis acidic triarylboranes as a catalyst, we can selectively effect C–H insertion, cyclopropanation, or ring-opening in good to excellent yields. Main group, or metal-free, catalysis has become a burgeoning field; yet, this flourishing field is still in its nascent stage. The work described herein represents a step toward improving the applicability of main group catalysis by employing metal-free approaches in the functionalization of organic compounds. This work demonstrates the highly selective metal-free catalytic reactions of α-aryl α-diazoesters with a range of (hetero)cycles and olefins using Lewis acidic boranes. The simple, mild reaction protocol employed represents an alternative to the commonly used precious metal systems and may provide future applications in the generation of biologically active compounds. Show more