Functionalized Cycloolefin Ligand as a Solution to Ortho -Constraint in the Catellani-Type Reaction.

The Catellani reaction, i.e., the Pd/norbornene (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 haloarene, referred to as " ortho -constraint". When an ortho substituent is absent, the substrate often fails to undergo an 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, this 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 cycloolefin ligand served as a covalent catalytic module to enable the ortho -alkylative Catellani reaction without NBE. In this work, we show that this chemistry could afford a new solution to ortho -constraint in the Catellani reaction. A functionalized 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 this 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.