Multiple Catalytic C−H Bond Functionalization for Natural Product Synthesis

Abstract

In the past decade, multiple catalytic C−H bond functionalization has been successfully applied in natural product synthesis as a strategy to reduce the number of steps, increase overall yield and employ more easily available starting materials. This minireview presents selected examples making use of multiple C−H bond functionalization in conceptually different ways. First, linear syntheses are discussed, wherein multiple C−H functionalization is employed either from simple (hetero)cyclic cores, at a late stage, or to build polycyclic systems. Second, the use of multiple C−H functionalization as a strategic tool in convergent synthesis to access and couple complex fragments is discussed. Information on the scalability of the employed methods is provided when available. The presented cases indicate that multiple C−H functionalization strategies should play a great role to shape the future synthesis of functional complex molecules with improved sustainability.

Mangana(iii/iv)electro-catalyzed C(sp3)–H azidation

“…The development of selective, resource-economic methods for the direct conversion of otherwise unreactive C(sp 3 )–H bonds is one of the most demanding challenges in molecular sciences. 1 Advances in this field will not only be of direct importance to petrochemical and polymer technologies, 2 but will also enable step-economical syntheses of pharmaceutical relevant compounds 3 by ideally late-stage drug diversification. 4 Within this topical research arena, concepts for direct C(sp 3 )–H aminations are particularly prominent.…”

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

“…Catalytic late-stage C-H functionalization, a highly efficient synthetic strategy, is regarded as a crucial tactic in the area of natural products, drug discovery, and medicinal chemistry [7][8][9][10][11][12] as it confers an invaluable synthetic opportunity for the facile diversification of biologically active complex molecules at the late stage. In recent years, much effort has been devoted Scheme 1: Mn-catalyzed late-stage fluorination of sclareolide (1) and complex steroid 3.…”

Evolution of Earth‐Abundant 3 d‐Metallaelectro‐Catalyzed C−H Activation: From Chelation‐Assistance to C−H Functionalization without Directing Groups

“…In sharp contrast, C−H activation [7] has emerged as an increasingly viable tool for improved sustainability with wide applications in natural product synthesis, [8] pharmaceuticals [9] and material sciences [10] . In oxidative C−H activation strategies, a C−H bond transforms into a stable C−metal bond that subsequently reacts with another C−H or Het−H functionality to result in a cross‐dehydrogenative transformation and the formation of the reduced metal species (Scheme 1).…”