Radical Carbonyl Propargylation by Dual Catalysis

• Published in: Angewandte Chemie International Edition Vol. 60; no. 5; pp. 2464 - 2471
• Main Authors: Huang, Huan‐Ming, Bellotti, Peter, Daniliuc, Constantin G., Glorius, Frank
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 01.02.2021; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alcohols; Aldehydes; Carbon; carbonyl; Carbonyl compounds; Carbonyls; Catalysis; Chemistry; Chemistry, Multidisciplinary; Chromium; Crossovers; dual catalysis; Functional groups; Photoredox catalysis; Physical Sciences; propargylation; radical-polar; Science & Technology; chromium; NICKEL CATALYSIS; PHOTOREDOX; ALLENIC ALCOHOLS; propargylation; ALDEHYDES; COPPER; dual catalysis; OXIDATIVE ADDITION; carbonyl; COUPLING REACTIONS; 1,3-ENYNES; OLEFINS; radical-polar; MOLECULAR-OXYGEN
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202011996

Carbonyl propargylation has been established as a valuable tool in the realm of carbon–carbon bond forming reactions. The 1,3‐enyne moiety has been recognized as an alternative pronucleophile in the above transformation through an ionic mechanism. Herein, we report for the first time, the radical carbonyl propargylation through dual chromium/photoredox catalysis. A library of valuable homopropargylic alcohols bearing all‐carbon quaternary centers could be obtained by a catalytic radical three‐component coupling of 1,3‐enynes, aldehydes and suitable radical precursors (41 examples). This redox‐neutral multi‐component reaction occurs under very mild conditions and shows high functional group tolerance. Remarkably, bench‐stable, non‐toxic, and inexpensive CrCl3 could be employed as a chromium source. Preliminary mechanistic investigations suggest a radical‐polar crossover mechanism, which offers a complementary and novel approach towards the preparation of valuable synthetic architectures from simple chemicals. Herein, the radical three‐component carbonyl propargylation between 1,3‐enynes, aldehydes, and suitable radical precursors through dual chromium/photoredox catalysis is reported for the first time. This redox‐neutral reaction occurs under very mild conditions, shows high functional group tolerance and represents a complementary novel approach for preparing valuable synthetic architectures from simple chemicals.