Room-Temperature Cu(II) Radical-Triggered Alkyne C-H Activation.

Jack Devonport,Lauren Sully,Matthew C Leech,George E Kostakis,Storm Hassell-Hart,Graham J Tizzard,Kevin Lam,Alaa Abdul-Sada,Alfredo Vargas,Simon J Coles,John Spencer,Athanassios K Boudalis

doi:10.1021/jacsau.1c00310

Abstract

A dimeric Cu(II) complex [Cu(II)2L2(μ2-Cl)Cl] (1) built from an asymmetric tridentate ligand (2-(((2-aminocyclohexyl)imino)methyl)-4,6-di-tert-butylphenol) and weakly coordinating anions has been synthesized and structurally characterized. In dichloromethane solution, 1 exists in a monomeric [Cu(II)LCl] (1′) (85%)–dimeric (1) (15%) equilibrium, and cyclic voltammetry (CV) and electron paramagnetic resonance (EPR) studies indicate structural stability and redox retention. Addition of phenylacetylene to the CH2Cl2 solution populates 1′ and leads to the formation of a transient radical species. Theoretical studies support this notion and show that the radical initiates an alkyne C–H bond activation process via a four-membered ring (Cu(II)–O···H–Calkyne) intermediate. This unusual C–H activation method is applicable for the efficient synthesis of propargylamines, without additives, within 16 h, at low loadings and in noncoordinating solvents including late-stage functionalization of important bioactive molecules. Single-crystal X-ray diffraction studies, postcatalysis, confirmed the framework’s stability and showed that the metal center preserves its oxidation state. The scope and limitations of this unconventional protocol are discussed.

Highlights

Copper catalysis is frequently used for molecular transformations of natural products, bioactive molecules, agrochemicals, and organic functional materials.[1−5] Coupling reactions involving terminal alkynes in the construction of new Csp−X bonds[3] are vital in the design of important organic scaffolds
Catalytic protocols involving well-characterized catalysts benefit from low trans-2-Aminocyclohexyl(imino)methyl)-4,6-di-tert-butylphenol hydrochloride, HL·HCl, was synthesized in two steps from loadings, reaction monitoring, and absence of additives
Given that the catalytic and cyclic voltammetry (CV) studies were performed at room temperature and the electron paramagnetic resonance (EPR) and single-crystal Xray diffraction (SXRD) studies were performed at 100 K, we considered that a variable-temperature

Summary

■ INTRODUCTION

A mixedvalent Cu(I/II) complex was crystallographically characterized from a Glaser coupling,[11] and dicopper Cu(I/I) and Cu(I/II) complexes were used in click chemistry.[12] monitoring of in situ generated species suggests a Cu(II)/ Cu(I) synergistic cooperation for alkyne C−H activation[13] or direct observation of reduction of Cu(II) to Cu(I) by terminal alkynes.[14] The general notion in organocopper chemistry is that the Cu(II)−carbon σ-bond is unstable and subject to spontaneous decomposition; it may be a key step in organic transformations.[4,5,15] These ideas suggest that more examples are needed to fully understand the role of Cu(II) species in terminal alkyne activation processes. JACS Au pubs.acs.org/jacsau screening protocols can result in useful conclusions and

■ RESULTS AND DISCUSSION

■ CONCLUSIONS

■ ACKNOWLEDGMENTS

■ REFERENCES