NICKEL METALLAPHOTOREDOX ENABLED PHOSPHONYLATION OF ALKYL BROMIDES

Abstract

Medicinal chemists rely on general and robust methodology to efficiently synthesize complex molecules that exhibit useful pharmacological activity. To this end, there has been much success in the development of coupling methods to form C-C, C-N, and C-O bonds, however methods to forge less ubiquitous heteroatom couplings, such as C-P bonds, remain elusive. Recently, the MacMillan group has leveraged the power of metallaphotoredox catalysis to develop a variety of cross coupling reactions under facile, room temperature conditions, enabling rapid access to previously unknown chemical space. This work takes advantage of these advancements in metallaphotoredox catalysis to develop a method towards the room-temperature formation of C-P bonds through the coupling of alkyl bromides with phosphite species, and its generality has been explored with an array of coupling partners. This methodology displays the versatility of metallaphotoredox cross coupling reactions in heteroatom linkage formation by enabling rapid access to a variety of alkyl phosphonates from readily available starting materials.