N-Heterocyclic Carbene (NHC) Catalyzed Synthesis of α,α-Difluoro Esters

Abstract

A process for the synthesis of α,α-difluoro esters by NHC-catalyzed fluorination is described. The internal redox process exhibits good efficiency, selectivity, and functional-group compatibility. It provides an alternative strategy for the formation of the useful gem-difluoromethylene unit in organic molecules.

Key words

carbenes - fluorine - umpolung - aldehydes - esterification

• References and Notes

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• 9 Typical Procedure In a glove box, an oven-dried 4 mL vial was charged with triazolium salt A (10.9 mg, 0.04 mmol), anhyd CHCl₃ (2 mL), K₃PO₄ (169.8 mg, 0.8 mmol), and enal 1a (0.2 mmol). Selectfluor (248 mg, 0.7 mmol) was then added, and the vial was capped and removed from the glove box. The reaction mixture was stirred at 50 °C for 17 h. The solvent was removed in vacuo, and the product 2a was purified by silica gel chromatography (10% EtOAc in hexanes) as colorless oil (68%). ¹H NMR (400 MHz, CDCl₃): δ = 7.44–7.40 (m, 2 H), 7.39–7.35 (m, 3 H), 7.11–7.06 (dt, J ₁ = 16.0 Hz, J ₂ = 2.4 Hz, 1 H), 6.35–6.26 (dt, J ₁ = 16.4 Hz, J ₂ = 11.6 Hz, 1 H), 3.91 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 164.4 (t, J = 35.0 Hz), 136.9 (t, J = 9.0 Hz), 134.0, 129.7, 128.8, 127.4, 118.7 (t, J = 25.0 Hz), 112.8 (t, J = 244.0 Hz), 53.5.