Enantioselective Amino- and Oxycyanation of Alkenes via Organic Photoredox and Copper Catalysis

Abstract

The β-amino nitrile moiety and its derivatives frequently appear in natural product synthesis, in drug design, and as ligands in asymmetric catalysis. Herein, we describe a direct route to these complex motifs through the amino-and oxycyanation of olefins utilizing an acridinium photooxidant in conjunction with copper catalysis. The transformation can be rendered asymmetric by using a serine-derived bisoxazoline ligand. Mechanistic studies implicate olefin-first oxidation. The scope of amines for the aminocyanation reaction has been greatly expanded by undergoing a cation radical intermediate as opposed to previous N-centered radical-initiated aminocyanations. Furthermore, alkyl carboxylic acids were included as nucleophiles in this type of transformation for the first time without any decarboxylative side reactions.

Recent advances in C(sp3)–N bond formation via metallaphoto-redox catalysis

“…By combining their previously developed alkene anti-Markovnikov hydrofunctionalization strategy with enantioselective radical cyanation, the Nicewicz group 45 recently developed a novel enantioselective aminocyanation of alkenes by merging photoredox and copper catalyses (Scheme 9a). Under the standard conditions, simple carbamate nucleophiles and nucleophilic azole compounds 62 can all participate in the reaction smoothly to afford the corresponding β-amino nitriles 63 in moderate to good yields with good enantioselectivities.…”

Bespoke All-in-one Metallaphotoredox Heterogeneous Catalysts for C-C Cross-Couplings

“…Meanwhile, synergistic catalysis imposes greater demands on the design of catalytic systems. In homogeneous metallaphotoredox catalysis, well-defined transition-metal complexes and photosensitizers could be designed through coordination chemistry, offering high activity and tunable light absorption to match different reactions (10)(11)(12)(13)(14)(15)(16)(17)(18). On the other hand, heterogeneous catalysts are preferred in industrial processes due to their high stability and recyclability (19-21).…”

Cu(I)-Photosensitizer-Catalyzed Olefin-α-Amino Radical Metathesis/Demethylenative Cyclization of 1,7-Enynes

“…The olefin functionality represents a fundamental scaffold and plays a ubiquitous role in the realm of chemical synthesis owing to its ready availability and versatile reactivity . In the last few decades, benefiting from the unique advantage of light energy in green and sustainable chemical synthesis, the radical-involved functionalization of olefins under visible-light-driven photocatalytic conditions provides a powerful and practical platform for the efficient construction of molecular complexity. − Generally, according to different radical intermediates involved, these transformations are classified into three scenarios: (1) radical reactions initiated by addition of a radical species to an olefin (Scheme A-a), (2) radical reactions initiated by single-electron oxidation of olefin to form a cationic radical intermediate (Scheme A-b), and (3) radical reactions initiated by single-electron reduction of olefin to form an anionic radical intermediate (Scheme A-c) . These scenarios provide divergent approaches to creating molecular complexity with olefins as feedstocks.…”