NOVEL STRATEGIES FOR A-HYDROXY C–H ARYLATION AND OXIDATIVE C–N CROSS COUPLING VIA METALLAPHOTOREDOX CATALYSIS

Abstract

Transition metal catalyzed cross-coupling is an incredibly powerful platform for the construction of organic architectures, since the advent of these technologies their impact has been felt throughout the chemical sciences and society more broadly. Despite the advances that have been made in this field over the last half century, limitations with respect to the ability to construct Csp3 rich frameworks, and carbon–heteroatom bonds with particularly electron deficient heteroatom coupling partners remains unsolved challenges. The moieties which would result from the realization of these transformations are of long-standing interest in the pharmaceutical industry, and academic medicinal chemistry discovery programs, due to unique biological properties they may possess.

Over the last decade photoredox catalysis has arisen as highly versatile platform for forging carbon–carbon and carbon–heteroatom bonds in a variety of molecular settings. In particular the merger of photoredox catalysis and transition metal catalysis has facilitated the development of a litany of new transformations which have the potential to vastly expedite the synthesis of organic frameworks of both academic and industrial interest, many of which have traditionally been difficult or impossible to access with prior art.

The design and development of a new paradigm for selective functionalization of C–H bonds adjacent to alcohols (an incredibly prevalent functional handle) is discussed. This strategy utilized a combination of three catalytic cycles in conjunction with a Lewis acid activation mode to access radical species from simple alcohols, which can then be cross coupled with aryl halides to deliver benzylic alcohol products in a highly modular fashion.

In addition, a novel cobalt photocatalyzed coupling of N-aryl amides and boronic acids is discussed. The development of a novel cobalt photoexcitation pathway facilitates the coupling of these partners via an open-shell homolytic substitution pathway. This methodology allows access to highly sterically encumbered diaryl amides in excellent yield, and also highlights the potential utility of base-metal chromophores in photocatalysis.