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

Yingang Ma; Jingxiang Pang; Xiaoguang Pan; Shutao Ma; Xigong Liu; Lei Liu

doi:10.1055/s-0040-1706408

Synlett, Table of Contents

Synlett 2020; 31(16): 1619-1622
DOI: 10.1055/s-0040-1706408

letter

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

Yingang Ma

^aDepartment of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, P. R. of China Email: mashutao@sdu.edu.cn Email: leiliu@sdu.edu.cn

,

Jingxiang Pang

^cShandong Medicinal Biotechnology Center, Key Laboratory for Rare & Uncommon Diseases of Shandong Province, Key Lab for Biotech-Drugs of National Health Commission, Institute of Materia Medica, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250000, P. R. of China

,

Xiaoguang Pan

^aDepartment of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, P. R. of China Email: mashutao@sdu.edu.cn Email: leiliu@sdu.edu.cn

,

Shutao Ma∗

^aDepartment of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, P. R. of China Email: mashutao@sdu.edu.cn Email: leiliu@sdu.edu.cn

,

Xigong Liu∗

^bSchool of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, P. R. of China

,

Lei Liu ∗

^aDepartment of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, P. R. of China Email: mashutao@sdu.edu.cn Email: leiliu@sdu.edu.cn

^bSchool of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, P. R. of China

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Abstract

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^◊ 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

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References

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.

Supplementary Material

Supporting Information

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

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