The Catellani reaction, i.e., the Pd/NBE catalysis, has been evolved into a versatile approach to multisubstituted arenes via the ortho-functionalization/ipso-termination process of a haloarene. Despite significant advances over the past 25 years, this reaction still suffered from an intrinsic limitation in the substitution pattern of the aryl halide, referred to as “ortho-constraint”. When an ortho substituent is absent, the haloarene substrate often fails to undergo effective mono ortho-functionalization process, and either ortho-difunctionalization products or NBE-embedded byproducts predominate. To tackle this challenge, structurally-modified NBEs (smNBEs) have been developed, which were proved effective for the mono ortho-aminative, -acylative, and -arylative Catellani reactions of ortho-unsubstituted haloarenes. However, the smNBE strategy is incompetent for solving the ortho-constraint in Catellani reactions with ortho-alkylation, and to date there lacks a general solution to this challenging but synthetically useful transformation. Recently, our group developed the Pd/olefin catalysis, in which an unstrained hybrid cycloolefin ligand served as a covalent catalytic module to enable the ortho-alkylative Catellani reaction without an NBE mediator. In this work, we show that this chemistry could afford a new solution to ortho-constraint in the Catellani reaction. A functionalized hybrid cycloolefin ligand bearing an amide group as the internal base was designed, which allowed for mono ortho-alkylative Catellani reaction of iodoarenes suffering from ortho-constraint before. Mechanistic study revealed that the newly designed ligand is capable of both accelerating the C−H activation and inhibiting side reactions, which accounts for its superior performance. The present work showcased the uniqueness of the Pd/olefin catalysis as well as the power of rational ligand design in metal catalysis.
New substrates and mechanistic experiments were included, together with more detailed mechanistic analysis.
Functionalized Cycloolefin Ligand as a New Solution to Ortho-Constraint in the Catellani-Type Reaction