Dialkyl Ether Formation at High-Valent Nickel.

Franck Le Vaillant,Markus Leutzsch,Edward J Reijerse,Josep Cornella

doi:10.1021/jacs.0c07381

Abstract

In this article, we investigated the I2-promoted cyclic dialkyl ether formation from 6-membered oxanickelacycles originally reported by Hillhouse. A detailed mechanistic investigation based on spectroscopic and crystallographic analysis revealed that a putative reductive elimination to forge C(sp3)–OC(sp3) using I2 might not be operative. We isolated a paramagnetic bimetallic NiIII intermediate featuring a unique Ni2(OR)2 (OR = alkoxide) diamond-like core complemented by a μ-iodo bridge between the two Ni centers, which remains stable at low temperatures, thus permitting its characterization by NMR, EPR, X-ray, and HRMS. At higher temperatures (>−10 °C), such bimetallic intermediate thermally decomposes to afford large amounts of elimination products together with iodoalkanols. Observation of the latter suggests that a C(sp3)–I bond reductive elimination occurs preferentially to any other challenging C–O bond reductive elimination. Formation of cyclized THF rings is then believed to occur through cyclization of an alcohol/alkoxide to the recently forged C(sp3)–I bond. The results of this article indicate that the use of F+ oxidants permits the challenging C(sp3)–OC(sp3) bond formation at a high-valent nickel center to proceed in good yields while minimizing deleterious elimination reactions. Preliminary investigations suggest the involvement of a high-valent bimetallic NiIII intermediate which rapidly extrudes the C–O bond product at remarkably low temperatures. The new set of conditions permitted the elusive synthesis of diethyl ether through reductive elimination, a remarkable feature currently beyond the scope of Ni.

Highlights

Dialkyl ethers constitute one of the most valuable functional groups, and their synthesis represents one of the oldest strategies to build chemical complexity
From a synthetic point of view, formation of the C−O bond has largely relied on the venerable Williamson ether synthesis,[2] which involves the union of an alcohol and an alkyl halide through a SN2 reaction in the presence of a strong base (Scheme 1A)
We considered that oxanickelacyles 1a and 1b provided an excellent platform to investigate an oxidative C(sp3)−OC(sp3) bond formation (Scheme 3)

Summary

■ INTRODUCTION

Dialkyl ethers constitute one of the most valuable functional groups, and their synthesis represents one of the oldest strategies to build chemical complexity. I2-Promoted C(sp3)−O−C(sp3) Bond Formation: (A) Hillhouse’s Seminal Work with Bipyridine Oxanickelacycles; (B) Love’s Example Using Strained Oxanickelacycle with Bidentate Phosphine and co-workers capitalized on the I2-promoted C−O bond formation and applied it to the oxanickelacyclobutane 1g bearing a 1,2-bis(di-tert-butylphosphino)ethane (dtbpe) as the ligand (Scheme 2B).[28] The authors observed rapid and clean formation of the corresponding epoxide in good yield along with almost quantitative formation of the corresponding (dtbpe)NiI2 (3). In this case, deleterious β-hydride elimination is not operative due to the presence of a ketone. High yields of the cyclized tetrahydrofurans were obtained

■ RESULTS AND DISCUSSION

■ CONCLUSIONS

■ ACKNOWLEDGMENTS

■ REFERENCES

H Coupling with Alcohols via Radical Relay Enabled by Redox