Use of Emerging C–H Functionalization Methods to Implement Strategies for the Divergent Total Syntheses of Bridged Polycyclic Natural Products

Carbon–hydrogen (C–H) bonds are ubiquitous in complex natural products. Over the past three decades, many methods to convert C–H bonds distal from functional groups, which were generally considered inert, have been developed. These advances now enable selective peripheral functionalizations at a late-stage. The direct engagement of traditionally unreactive C–H bonds in reactions expands chemical space by reducing functional group interconversions. As such, C–H functionalization serves as a powerful tool in medicinal and agrochemical chemistry as well as in the total synthesis of natural products where diversification to a broad array of compounds from a common intermediate is often desired. In this Account, we detail the thought processes and design principles that relied on emerging methods for C–H functionalization to prepare a wide range of bridged, polycyclic, natural products in the cephalotane and longibornane families from a common intermediate in each case.