A Paradigm Shift in Catalysis: Electro- and Photomediated Nickel-Catalyzed Cross-Coupling Reactions

Abstract

Transition-metal cata-lyzed cross-coupling reactions are fundamental reactions in organic chemistry, facilitating strategic bond formations for accessing natural products, organic mate-rials, agrochemicals, and pharmaceuticals. Redox chemistry enables access to elusive cross-coupling mechanisms through single-electron processes as an alternative to classical two-electron strategies, which are predominated by palladium catalysis. The hallmark of this redox platform is the systematic modulation of transition-metal oxidation states by a photoredox catalyst or at a heterogeneous electrode sur-face. Electrocatalysis and photocatalysis enhance transition metal catalysis’ capacity for bond formation through electron- or energy-transfer processes. Cross-coupling conditions promoted by electrocatalysis and photocatalysis are mild and bond formation proceeds with exceptionally high chemoselectivity and wide functional group tolerance. The interfacing of abundant first-row transition-metal catalysis with electrocatalysis and photocatalysis has brought about a paradigm shift in cross-coupling technology. In particular, the merger of Ni catalysis with electro- and photochemistry ushered in a new era for carbon-carbon and carbon-heteroatom cross-couplings. We have developed enabling photo- and electrochemical methods throughout our research experience in industry (BMS, AstraZeneca), academia (Professor Baran, Scripps Research), and cross-disciplinary collaborative environments. In this Account, we will outline recent progress from our past and present labs in photo- and electrochemically mediated Ni-catalyzed cross-couplings. By highlighting these cross-coupling methodologies, we will also compare mechanistic features of both electro– and photochemical strategies for forging C(sp2)–C(sp3), C(sp3)–C(sp3), C–O, C–N, and C–S bonds. In each case study where we did not specifically develop both approaches, we will highlight related work from others for education. Through these side-by-side comparisons, we hope to demystify the subtle differences between the two complementary tools to enact redox control over transition metal catalysis. Finally, building off the collective experience of ourselves and the rest of the community, we propose a user guide to photo- and electrochemically-driven cross-coupling reactions to aid the practitioner in rapidly applying such tools in their synthetic designs.

Redox-Active Thiocarbonyl Auxiliaries in Ni-Catalyzed Cross-Couplings of Aliphatic Alcohols

“…Despite this, a range of other electron-rich arylzinc nucleophiles (Scheme , 53l – 53n ), and heteroaryl species ( 53o, 53p ) were compatible. The success of electron-rich aryl coupling partners is significant given that these fragments are often unsuccessful using alternative reductive cross-coupling strategies involving aryl halides and tertiary aliphatic radical precursors . In cases were electron-neutral (hetero)­arylzinc reagents gave lower yields, we found that the desired product could be obtained in higher quantities if p -methoxyphenyl thionoester 54a was used as the redox-active starting material instead of 51b …”