Dialkyl Ether Formation at High-Valent Nickel

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 Ni^III 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 Ni^III 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.

Scheme 1. (A) Williamson Ether Synthesis (Advantages and Pitfalls); (B) Existing Methods for C(sp²)–O Bond Formation Using Ni Catalysts; (C) C(sp³)–O–C(sp³) Bond Formation from High-Valent Ni

Scheme 2. 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

Scheme 3. Synthetic Route to Oxanickelacyclohexanes

This yield comprises a mixture of 85:15 of 1b and 1b-isomer.

Figure 1

Cyclic voltammogram of 1b (1.0 mM) in CD₃CN, recorded versus Ag/AgNO₃ electrode, using n-Bu₄NPF₆ (0.2 M) as electrolyte, under argon, with a scan rate of 100 mV·s^–1. Potentials are then converted to the Fc/Fc⁺ couple.

Scheme 4. Attempts to C–O Bond Formation after One-Electron Oxidation of 1b To Access High-Valent Ni^III

Scheme 5. (A) Hillhouse I₂-Promoted C(sp³)–O–C(sp³) Bond Formation Reaction (Analysis of the Fate of the Organic and Inorganic Compounds); (B) X-ray Structure of Complex 8; (C) Ni^III Bimetallic Intermediate 9a–b; (D) ¹H NMR of Paramagnetic Complex 9a(31)

Disordered iodine atoms are omitted for clarity. Selected distances (Angstroms): Ni1–I1 = N2–I2 = 2.78; Ni1–I2 = Ni2–I1 = 2.83; Ni1–N1 = Ni1–N2 = 2.07. Selected angles (degrees): I1–Ni–I2 = 89.2; Ni1–I1–Ni2 = 94.2. Insets correspond to peaks at 237, −98, and −930 ppm.

Figure 2

X-ray structure of compound 9a. Hydrogen atoms and disordered iodide atoms in I₃^– counterion are omitted for clarity. Selected distances (Angstroms): Ni1–Ni2 = 2.84; Ni1–I1 = Ni2–I1 = 2.92; Ni1–O1 = Ni1–O2 = Ni2–O1 = Ni2–O2 = 2.00; Ni1–N1 = 1.99; Ni1–N2 = 2.05; Ni1–C1 = 2.013. Selected angles (degrees): Ni1–I1–Ni2 = 58.07; Ni1–O1–Ni2 = 92.72; O1–Ni1–O2 = 79.57.

Figure 3

X-band EPR (9.623 GHz) of complexes 9a and 9b recorded at 30 K (blue traces). Experimental parameters: 1 mW, 100 kHz, 7.5 G field modulation. Red traces represent the Easyspin (esfit) simulation with the following parameters: g(9a) = (2.081, 2.155, 2.279); g(9b) = (2.084, 2.144, 2.287). Dipolar interaction D(9b) = 517 MHz; D(9a) = 550 MHz. J coupling < 50 MHz.

Scheme 6. Thermal Decomposition of Complex 9b and Hypothetical S_N2 Reaction from 7b

Scheme 7. (A) Screening of Oxidants for the Oxidatively Induced C(sp³)–OC(sp³) Bond Formation; (B) Application to the Synthesis of THF

Reaction conditions: oxanickelacycle 1b (1 equiv), oxidant 10 (1.05 equiv) in CD₃CN or CD₂Cl₂ at 25 °C.

Scheme 8. (A) Synthesis of (bipy)NiEt₂11 and (bipy)Ni(Et)(OEt) 1f; (B) Oxidatively Induced Synthesis of Diethyl Ether from Nickel Complex 1f

Reaction conditions: (step 1) Ni(acac)₂ (1 equiv), bipy (1 equiv) Et₂AlOEt (3 equiv) in Et₂O, from −50 to 25 °C, 50 h, 11 87% isolated yield; (step 2) 11 (1 equiv), N₂O (1 atm) in THF at 25 °C, 1f 63% isolated yield. Reaction conditions: oxanickelacycle 1f (1 equiv), 10e and 10f (1.05 equiv) in CD₃CN at 25 °C, 1 min. Yields determined by ¹H NMR using mesitylene as internal standard.

Scheme 9. (A) EPR of int-I at 20 K; (B) Mass Spectrometry Results and Postulated Mechanistic Pathways

Experimental conditions: Power = 2.0 mW, modulation (100 kHz) amplitude 7.5 G. Dotted red trace represents the Easyspin (esfit) simulation with parameters g = (2.103, 2.200, 2.227). Dipolar interaction D(int-I) = 299 MHz. J coupling = 100 MHz.