Transition‐Metal‐Free Formal Sonogashira Coupling and α‐Carbonyl Arylation Reactions |
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Authors: | Birgit Prüger Dr. Gretchen E. Hofmeister Prof. Dr. Christian Borch Jacobsen David G. Alberg Prof. Dr. Martin Nielsen Dr. Karl Anker Jørgensen Prof. Dr. |
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Affiliation: | 1. Center for Catalysis, Department of Chemistry, Aarhus University, 8000 Aarhus C (Denmark), Fax: (+45) 8619‐6199;2. Department of Chemistry, Carleton College, Northfield, MN 55057 (USA) |
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Abstract: | Transition‐metal‐free formal Sonogashira coupling and α‐carbonyl arylation reactions have been developed. These transformations are based on the nucleophilic aromatic substitution (SNAr) of β‐carbonyl sulfones to electron‐deficient aryl fluorides, producing a key intermediate that, depending on the reaction conditions, gives the aromatic alkynes or α‐aryl carbonyl compounds. The development of these reactions is presented and, based on investigations under basic and acidic conditions, mechanisms have been proposed. To develop the formal Sonogashira coupling further, a milder, two‐step protocol is also disclosed that expands the reaction concept. The scope of these reactions is demonstrated for the synthesis of Sonogashira and α‐carbonyl arylated products from a range of electron‐deficient aryl fluorides with a variety of functional groups and aryl‐, heteroaryl‐, alkyl‐, and alkoxy‐substituted sulfone nucleophiles. These transition‐metal‐free reactions complement the metal‐catalyzed versions in terms of substitution patterns, simplicity, and reaction conditions. |
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Keywords: | alkynes aromatic substitution C?C coupling cross‐coupling metal‐free synthesis |
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