Transition-metal-free formal Sonogashira coupling and alpha-carbonyl arylation reactions.
Transition-metal-free formal Sonogashira coupling and alpha-carbonyl arylation reactions have been developed. These transformations are based on the nucleophilic aromatic substitution (S(N)Ar) of beta-carbonyl sulfones to electron-deficient aryl fluorides, producing a key intermediate that, depending on the reaction conditions, gives the aromatic alkynes or alpha-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 alpha-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.
Prüger
Birgit
B
Center for Catalysis, Department of Chemistry, Aarhus University, 8000 Aarhus C, Denmark.
Hofmeister
Gretchen E
GE
Jacobsen
Christian Borch
CB
Alberg
David G
DG
Nielsen
Martin
M
Jørgensen
Karl Anker
KA