Catalytic and Photochemical Strategies to Stabilized Radicals Based on Anomeric Nucleophiles

• Published in: Journal of the American Chemical Society Vol. 142; no. 25; pp. 11102 - 11113
• Main Authors: Zhu, Feng, Zhang, Shuo-qing, Chen, Zhenhao, Rui, Jinyan, Hong, Xin, Walczak, Maciej A
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 24.06.2020; Amer Chemical Soc
• Subjects: blue light; carbohydrates; carbon; Catalysis - radiation effects; catalytic activity; cell communication; chemical bonding; Chemistry; Chemistry, Multidisciplinary; Coordination Complexes - chemistry; Coordination Complexes - radiation effects; copper; Copper - chemistry; Copper - radiation effects; cross-coupling reactions; Density Functional Theory; disulfides; drugs; free radicals; Free Radicals - chemistry; Glycosylation; irradiation; Lewis acids; Lewis bases; Light; Models, Chemical; Organotin Compounds - chemistry; Organotin Compounds - radiation effects; photochemistry; Physical Sciences; Science & Technology; stereoselectivity; sulfur; Thioglycosides - chemical synthesis; DESIGN; ALKYL; NICKEL; COUPLING REACTIONS; ACIDS; CONSTRUCTION; ARYL; REDOX-ACTIVE ESTERS; C-GLYCOSIDES; PHOTOREDOX CATALYSIS
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/jacs.0c03298

Carbohydrates, one of the three primary macromolecules of living organisms, play significant roles in various biological processes such as intercellular communication, cell recognition, and immune activity. While the majority of established methods for the installation of carbohydrates through the anomeric carbon rely on nucleophilic displacement, anomeric radicals represent an attractive alternative because of their functional group compatibility and high anomeric selectivities. Herein, we demonstrate that anomeric nucleophiles such as C1 stannanes can be converted into anomeric radicals by merging Cu­(I) catalysis with blue light irradiation to achieve highly stereoselective C­(sp3)–S cross-coupling reactions. Mechanistic studies and DFT calculations revealed that the C–S bond-forming step occurs via the transfer of the anomeric radical directly to a sulfur electrophile bound to Cu­(II) species. This pathway complements a radical chain observed for photochemical metal-free conditions where a disulfide initiator can be activated by a Lewis base additive. Both strategies utilize anomeric nucleophiles as efficient radical donors and achieve a switch from an ionic to a radical pathway. Taken together, the stability of glycosyl nucleophiles, a broad substrate scope, and high anomeric selectivities observed for the thermal and photochemical protocols make this novel C–S cross coupling a practical tool for late-stage glycodiversification of bioactive natural products and drug candidates.