Catalytic Multicomponent Synthesis of C‐Acyl Glycosides by Consecutive Cross‐Electrophile Couplings

• Published in: Angewandte Chemie International Edition Vol. 61; no. 46; pp. e202211043 - n/a
• Main Authors: Jiang, Yi, Yang, Kai, Wei, Yi, Wang, Quanquan, Li, Shi‐Jun, Lan, Yu, Koh, Ming Joo
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 14.11.2022; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: C-Acyl Glycoside; Catalysis; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; Chloroformate; Coupling (molecular); Couplings; Cross coupling; Cross-Electrophile Coupling; Glycosides; Glycosides - chemistry; Glycosylation; Halides; Intermediates; Multicomponent; Natural products; Nickel - chemistry; Nickel Catalysis; Oligopeptides; Physical Sciences; Science & Technology; Stereoselective; Transition metals; REAGENTS; ALPHA-GALACTOSYLCERAMIDE; ACIDS; ANALOGS; ALKYL-HALIDES; KETONES; Nickel Catalysis; ARYL; Cross-Electrophile Coupling; Multicomponent; C-Acyl Glycoside; ACCESS; Stereoselective
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202211043

C‐Acyl glycosides are versatile intermediates to natural products and medicinally relevant entities. Conventional cross‐coupling strategies to secure these molecules often relied on two‐component manifolds in which a glycosyl precursor is coupled with an acyl donor (pre‐synthesized or generated in situ) under transition metal or dual catalysis to forge a C−C bond. Here, we disclose a three‐component Ni‐catalyzed reductive regime that facilitates the chemoselective union of glycosyl halides, organoiodides and commercially available isobutyl chloroformate as a CO surrogate. The method tolerates multiple functionalities and the resulting products are obtained in high diastereoselectivities. Theoretical calculations provide a mechanistic rationale for the unexpectedly high chemoselectivity of sequential cross‐electrophile couplings. This approach enables the expeditious assembly of difficult‐to‐synthesize C‐acyl glycosides, as well as late‐stage keto‐glycosylation of oligopeptides. Reductive nickel catalysis was leveraged to orchestrate the multicomponent union of glycosyl halides, organoiodides and isobutyl chloroformate to assemble C‐acyl glycosides in high anomeric selectivities. Computational studies provided insights that rationalize the origin of the high chemoselectivity. The method is applicable to the synthesis of complex C‐linked disaccharides and late‐stage keto‐glycosylation of peptides.