No abstract

We report a dual-tasked methylation that is based on cooperative palladium/norbornene catalysis. Readily available (hetero)aryl halides (39 iodides and 4 bromides) and inexpensive MeOTs or trimethylphosphate are utilized as the substrates and methylating reagent, respectively. Six types of "ipso" terminations can modularly couple with this "ortho" C−H methylation to constitute a versatile methylation toolbox for preparing diversified methylated arenes. This toolbox features inexpensive methyl sources, excellent functional-group tolerance, simple reaction procedures, and scalability. Importantly, it can be uneventfully extended to isotope-labeled methylation by switching to the corresponding reagents CD 3 OTs or 13 CH 3 OTs. Moreover, this toolbox can be applied to late-stage modification of biorelevant substrates with complete stereoretention. We believe these salient and practical features of our dual-tasked methylation toolbox will be welcomed by academic and industrial researchers.

A cooperative catalytic system comprising a palladium/XPhos complex and 5-norbornene-2-carboxylic acid was developed. This system promotes a two-component annulation reaction, allowing the construction of tetrahydronaphthalenes and indanes that contain quaternary centers through consecutive Catellani-type C−H activation and redoxrelay Heck reaction. Inexpensive 5-norbornene-2-carboxylic acid acts as a catalytic mediator (20 mol %) in this process. This mild, scalable, and chemoselective protocol is compatible with a wide variety of readily available aryl iodides and alkylating reagents. Application of this method in a 4-step synthesis of opioid analgesic eptazocine is demonstrated. Preliminary studies underscore the future promise of rendering this Catellani/redox-relay Heck cascade enantioselective.

Herein, we report a modular and convergent strategy for the assembly of atropisomeric o-terphenyls with 1,2-diaxes via palladium/chiral norbornene cooperative catalysis and axial-to-axial diastereoinduction. Readily available aryl iodides, 2,6-substituted aryl bromides, and potassium aryl trifluoroborates are used as the building blocks, laying the foundation for diversity-oriented synthesis of these scaffolds (46 examples). Other features include the unique axial-to-axial diastereoinduction mode, construction of two axes in a single operation, and step economy. DFT calculations are performed to rationalize the axial-to-axial diastereoinduction process. Synthetic utilities of this method in preparation of atropisomeric oligophenyls, chiral catalysts, and ligands are demonstrated.

The Catellani reaction is a powerful strategy that allows the expeditious synthesis of highly substituted arenes, which are not easily accessible through traditional transition-metal-catalyzed cross-coupling reactions. This reaction utilizes the synergistic interplay of palladium and norbornene catalysis to facilitate sequential ortho-C-H functionalization and ipso termination of aryl iodides in a single operation. Since pioneering work by the group of Catellani in 1997, and later by the group of Lautens, this chemistry has attracted considerable attention from the synthetic chemistry community. Dramatic progress has been made by a number of groups in the past two decades. In this Minireview, the alkylating reagents employed in this intriguing reaction and the corresponding applications in organic synthesis are summarized; thus complementing existing reviews to inspire future developments.