Iron-Catalyzed Enantioselective Multicomponent Cross-Couplings of α‑Boryl Radicals

• Published in: Organic letters Vol. 25; no. 46; pp. 8320 - 8325
• Main Authors: Youshaw, Cassandra R., Yang, Ming-Hsiu, Gogoi, Achyut Ranjan, Rentería-Gómez, Angel, Liu, Lei, Morehead, Lukas M., Gutierrez, Osvaldo
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 24.11.2023; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Letter; Physical Sciences; Science & Technology; FLUORINE; DICARBOFUNCTIONALIZATION; ALKENYL HALIDES; MECHANISM; GRIGNARD-REAGENTS
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/acs.orglett.3c03387

Despite recent interest in the development of iron-catalyzed transformations, methods that use iron-based catalysts capable of controlling the enantioselectivity in carbon–carbon cross-couplings are underdeveloped. Herein, we report a practical and simple protocol that uses commercially available and expensive iron salts in combination with chiral bisphosphine ligands to enable the regio- and enantioselective (up to 91:9) multicomponent cross-coupling of vinyl boronates, (fluoro)­alkyl halides, and Grignard reagents. Preliminary mechanistic studies are consistent with rapid formation of an α-boryl radical followed by reversible radical addition to monoaryl bisphosphine-Fe­(II) and subsequent enantioselective inner-sphere reductive elimination. From a broader perspective, this work provides a blueprint to develop asymmetric Fe-catalyzed multicomponent cross-couplings via the use of alkenes as linchpins to translocate alkyl radicals, modify their steric and electronic properties, and induce stereocontrol.