One-Pot Synthesis of Oxiranes through Vicarious Nucleophilic Substitution (VNS)–Darzens Reaction

Abstract

Oxiranes are formed in a highly diastereoselective one-pot process, in which aldehydes react with α-chloronitrobenzylic carbanions produced in the vicarious nucleophilic substitution (VNS) reaction of nitroarenes with tert-butyl dichloroacetate.

Key words

epoxides - Darzens reaction - nucleophilic substitution - ­nitro compounds - aldehydes

• References and Notes

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• 11 General experimental procedure: To a vigorously stirred suspension of potassium tert-butoxide (2.1 mmol, 236 mg) in anhydrous DMF (3 mL) prepared in a Schlenk flask under Ar and cooled to –5 °C, a solution of nitroarene (1 mmol) and tert-butyl dichloroacetate (1.1 mmol, 204 mg) in DMF (1 mL) was added dropwise. After 5 min, a solution of aldehyde (3 mmol) in DMF (2 mL) was added and the homogeneous, dark-violet or dark-blue reaction mixture was placed in a freezer at –22 °C for four days. The reaction mixture was poured in water (20 mL), and the product was extracted with dichloromethane (3 × 15 mL). The combined extract was washed with brine (3 × 20 mL) and dried over Na₂SO₄, and the solvent was evaporated. The products were purified by column chromatography on silica gel (hexanes–EtOAc). Oxirane 2j (158 mg, 39%), which was obtained as pale-yellow crystals, was recrystallized from hexanes solution by slow evaporation; mp 115–117 °C. IR (CH₂Cl₂): 3105, 2980, 2934, 2230, 1742, 1527, 1343, 1156, 840 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.41 (s, 9 H), 5.01 (s, 1 H), 7.24 (d, ³ J _H–H = 8.2 Hz, 2 H), 7.39 (dd, ³ J _H–H = 8.8 Hz, ⁴ J _H–H = 2.4 Hz, 1 H), 7.44 (d, ³ J _H–H = 8.4 Hz, 2 H), 7.75 (m, 1 H), 7.92 (d, ³ J _H–H = 8.8 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 27.6, 63.5, 65.3, 84.6, 112.4, 118.2, 125.9, 127.1, 128.1, 129.7, 130.4, 131.8, 137.7, 140.4, 145.8, 165.0. HRMS (ESI): m/z [M + Na] calcd for C₂₀H₁₇N₂O₅ClNa: 423.0724; found: 423.0712.