Iron-Catalyzed Carbenoid Insertion into C(sp³)–H Bonds

Abstract

An iron-catalyzed carbenoid insertion into C–H bonds of alkanes was developed with high activity (turnover numbers up to 690 in a gram-scale experiment) and chemoselectivity. This non-heme iron-catalyzed C(sp³)–H insertion reaction provides an efficient strategy for C–H functionalization.

Key words

iron catalysis - carbenoid insertion - C–H functionalization - chemoselectivity - diazo compounds - alkanes

• References and Notes


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• 12 Methyl 2-cyclohexyl-2-phenylacetate (3aa); Typical Procedure: Powered Fe(ClO₄)₂·xH₂O (1.0 mg, 0.003 mmol, 1 mol%), ligand 12 (1.0 mg, 0.0036 mmol, 1.2 mol%), and NaBAr_F (3.4 mg, 0.0036 mmol, 1.2 mol%) were introduced into an oven-dried Schlenk tube in an argon-filled glovebox. After CHCl₃ (1 mL) was injected into the Schlenk tube, the solution was stirred at 25 °C under argon atmosphere for 4 h. Cyclohexane (2a; 3 mL) and methyl α-diazophenylacetate (1a; 52.9 mg, 0.3 mmol) were then successively introduced into the system. The resulting mixture was stirred at a bath temperature of 95 °C for 36 h. After concentration in vacuo, the residue was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate, 30:1 v/v) to give methyl 2-cyclohexyl-2-phenylacetate (3aa) as a colorless oil. Yield: 57.2 mg (0.246 mmol, 82%). ¹H NMR (400 MHz, CDCl₃): δ = 7.39–7.20 (m, 5 H), 3.64 (s, 3 H), 3.22 (d, J = 10.7 Hz, 1 H), 2.08–1.94 (m, 1 H), 1.83–1.57 (m, 4 H), 1.33–0.99 (m, 5 H), 0.79–0.68 (m, 1 H). ¹³C NMR (101 MHz, CDCl₃): δ = 174.4, 137.8, 128.5, 128.4, 127.1, 58.8, 51.7, 41.0, 32.0, 30.4, 26.3, 26.0, 25.9.