Chapter 1 – Recent Accomplishments in the Total Synthesis of Natural Products Through C–H Functionalization Strategies

Abstract Over the last century, high levels of creativity and structural complexity have been achieved in the synthesis of natural products, mostly motivated by the desire to utilize the intriguing bioactivities that these molecules offer for the benefit of society. From the marine depths to the microscopic world of bacterial cultures, nature affords an endless source of structural diversity which has inspired continuous research into chemical processes, from the isolation of a molecule to the production of a drug or its derivatives. Almost any molecule targeted by the synthetic chemist can now be made and this ability to manufacture molecules underpins our current knowledge in chemical sciences and a whole range of advances in technology. Nevertheless, supplying complex natural products to satisfy the demands of society remains a challenging task. Factors such as environmental regulations and synthetic efficiency (yields, number of steps, time, or costs) have sometimes limited the production of important molecules in both industrial and academic contexts. However, it is possible to overcome some of these limitations through synthetic planning using established and new reactions which transform C–H bonds and thereby expand their functionality in valuable ways. In other words, in the field of C–H functionalization, we can uncover previously hidden synthetic routes and new tools which enable us to come up with new syntheses of complex organic compounds. In this chapter, we present some recent examples of the ways in which state-of-the art C–H functionalization has been applied in total synthesis encompassing different families of natural products.