Modular radical cross-coupling with sulfones enables access to sp 3 -rich (fluoro)alkylated scaffolds.

Autor: Merchant RR; Department of Chemistry, The Scripps Research Institute (TSRI), 10550 North Torrey Pines Road, La Jolla, CA 92037, USA., Edwards JT; Department of Chemistry, The Scripps Research Institute (TSRI), 10550 North Torrey Pines Road, La Jolla, CA 92037, USA., Qin T; Department of Chemistry, The Scripps Research Institute (TSRI), 10550 North Torrey Pines Road, La Jolla, CA 92037, USA., Kruszyk MM; Department of Chemistry, The Scripps Research Institute (TSRI), 10550 North Torrey Pines Road, La Jolla, CA 92037, USA., Bi C; Department of Chemistry, The Scripps Research Institute (TSRI), 10550 North Torrey Pines Road, La Jolla, CA 92037, USA., Che G; Asymchem Life Science (Tianjin), Tianjin Economic-Technological Development Zone, Tianjin 300457, China., Bao DH; Asymchem Life Science (Tianjin), Tianjin Economic-Technological Development Zone, Tianjin 300457, China., Qiao W; Asymchem Life Science (Tianjin), Tianjin Economic-Technological Development Zone, Tianjin 300457, China., Sun L; Asymchem Life Science (Tianjin), Tianjin Economic-Technological Development Zone, Tianjin 300457, China., Collins MR; Department of Chemistry, La Jolla Laboratories, Pfizer, 10770 Science Center Drive, San Diego, CA 92121, USA., Fadeyi OO; Pfizer Medicinal Sciences, Eastern Point Road, Groton, CT 06340, USA., Gallego GM; Department of Chemistry, La Jolla Laboratories, Pfizer, 10770 Science Center Drive, San Diego, CA 92121, USA., Mousseau JJ; Pfizer Medicinal Sciences, Eastern Point Road, Groton, CT 06340, USA., Nuhant P; Pfizer Medicinal Sciences, Eastern Point Road, Groton, CT 06340, USA., Baran PS; Department of Chemistry, The Scripps Research Institute (TSRI), 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. pbaran@scripps.edu.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2018 Apr 06; Vol. 360 (6384), pp. 75-80. Date of Electronic Publication: 2018 Feb 18.
DOI: 10.1126/science.aar7335
Abstrakt: Cross-coupling chemistry is widely applied to carbon-carbon bond formation in the synthesis of medicines, agrochemicals, and other functional materials. Recently, single-electron-induced variants of this reaction class have proven particularly useful in the formation of C(sp 2 )-C(sp 3 ) linkages, although certain compound classes have remained a challenge. Here, we report the use of sulfones to activate the alkyl coupling partner in nickel-catalyzed radical cross-coupling with aryl zinc reagents. This method's tolerance of fluoroalkyl substituents proved particularly advantageous for the streamlined preparation of pharmaceutically oriented fluorinated scaffolds that previously required multiple steps, toxic reagents, and nonmodular retrosynthetic blueprints. Five specific sulfone reagents facilitate the rapid assembly of a vast set of compounds, many of which contain challenging fluorination patterns.
(Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje