Dual Nickel-/Palladium-Catalyzed Reductive Cross-Coupling Reactions between Two Phenol Derivatives

Abstract

Cross-coupling between substrates that can be easily derived from phenols is highly attractive due to the abundance and low cost of phenols. Here, we report a dual nickel/palladium-catalyzed reductive cross-coupling between aryl tosylates and aryl triflates; both substrates can be accessed in just one step from readily available phenols. The reaction has a broad functional group tolerance and substrate scope (>60 examples). Furthermore, it displays low sensitivity to steric effects demonstrated by the synthesis of a 2,2'disubstituted biaryl and a fully substituted aryl product. The widespread presence of phenols in natural products and pharmaceuticals allow for straightforward late-stage functionalization, illustrated with examples such as Ezetimibe and tyrosine. NMR spectroscopy and DFT calculations indicate that the nickel catalyst is responsible for activating the aryl triflate, while the palladium catalyst preferentially reacts with the aryl tosylate.File list (2) download file view on ChemRxiv Manuscript v7 ChemRxiv.pdf (705.67 KiB) download file view on ChemRxiv 1 Supporting Information v2.pdf (9.12 MiB)

C(sp2)–C(sp2) Reductive Cross-Coupling of Triarylphosphines with Aryl Halides by Palladium/Nickel Co-catalysis

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Nickel-Catalyzed Reductive Cross-Coupling of Heteroaryl Chlorides and Aryl Chlorides

“…This strategy relied on the selective oxidative addition of two catalysts into each of the aryl electrophiles; the nickel catalyst favored oxidative addition into the C–Br bond, while the palladium catalyst favored oxidative addition into the C–OTf bond. The use of multimetallic catalyst systems have since been developed to address challenges associated with C­(sp 2 )–C­(sp 2 ) cross-coupling …”

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“…Also in 2020, Zhong et al reported another dual nickel-/palladium-catalyzed reductive cross-coupling between aryl tosylates 253 and aryl triflates 254, both of which could be easily accessed from readily available phenols 252. 70 By combining different ligands, Pd/L1 selectively activates the tosylate C-O bond, while Ni/L2 prefers to activate the triflate, leading overall to the formation of crosscoupling products 255 (Scheme 49).…”