Remote functionalization of stereodefined substituted cyclopropanes: Toward synthetically useful acyclic fragments

Over the past several decades, many efforts have been directed to achieve robust methods for the construction of acyclic molecules bearing stereodefined chiral centers. The flexibility of an acyclic molecule represents a significant synthetic challenge. Among other excellent methods, our group has established several new approaches toward this important issue. In this context, we recently turned our attention to the catalytic palladium Heck arylation for the remote ring-opening of ω-ene cyclopropanes allowing the creation of up to 3 acyclic new stereocenters by triggering a metal-walk process revealing the desired acyclic molecular backbone. the rigid three-membered ring serves as a template for forging few controlled stereocenters, and the selective opening of the strained cycle reveal them, now on an acyclic chain.

In this work, we apply this oxidative Heck reaction for the selective opening of vinyl cyclopropanes. This allows us to obtain valuable compounds such as fully substituted lactoles and acyclic chains bearing two stereocenters in a 1,5 relationship which is present in many natural molecules like alpha-Tocopherol (vitamin E). We are also putting efforts into adjusting our conditions for revealing heteroatom-substituted stereocenter, which is challenging under transition metal catalysis.