Synthesis of Unsymmetric Triarylmethanes Bearing CF₃-Substituted All-Carbon Quaternary Stereocenters: 1,6-Arylation of δ-Trifluo­romethyl Substituted para-Quinone Methides

^◊ These authors contributed equally to this work.

Abstract

Pre-synthesized δ-CF₃-δ-aryl-disubstituted para-quinone methides bearing δ-substituents were identified as isolable and storable substrates for 1,6-arylation reactions. A broad range of electron-rich arenes and heteroarenes participated in the arylation process, furnishing a wide array of unsymmetrical CF₃-substituted triarylmethanes in high efficiency. The mild and expeditious protocol exhibited broad scopes of both arene and para-quinone methide components.

Key words

triarylmethanes - trifluoromethyl - para-quinone methide - quaternary center - 1,6-arylation

• References and Notes

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• 13 2,6-Dimethyl-4-[2,2,2-trifluoro-1-(4-hydroxyphenyl)-1-phenylethyl]phenol (3a) – Typical Procedure To a solution of 1a (0.1 mmol, 1.0 equiv) in CH₂Cl₂ (3.0 mL) was successively added Bi(OTf)₃ (0.01 mmol, 0.1 equiv) and 2a (0.12 mmol, 1.2 equiv) at room temperature. The mixture was stirred at the same temperature and monitored by TLC until the complete conversion of 1a. Then the reaction was concentrated and purified by a flash column chromatography on silica gel using EtOAc/PE (10:90) as eluent to afford 3a (35.7 mg, 96%). ¹H NMR (500 MHz, CDCl₃): δ = 7.35–7.29 (m, 3 H), 7.20–7.13 (m, 2 H), 7.01 (d, J = 8.8 Hz, 2 H), 6.77 (d, J = 8.9 Hz, 2 H), 6.73 (s, 2 H), 4.85 (s, 1 H), 4.66 (s, 1 H), 2.18 (s, 6 H). ¹³C NMR (126 MHz, CDCl₃): δ = 154.9, 151.7, 140.9, 133.1, 132.1, 131.6, 130.4, 130.1, 128.4 (q, J = 286.0 Hz), 128.2, 127.7, 122.6, 115.0, 64.2 (q, J = 23.8 Hz), 16.4. ¹⁹F NMR (471 MHz, CDCl₃): δ = –58.6. HRMS (ESI): m/z calcd for C₂₂H₁₈F₃O₂ [M – H]^–: 371.1264; found: 371.1260.