Addition of Alcohols onto Electron-Deficient Heteroarenium Salts: A Reversible Covalent Bonding Process under Basic Conditions

Baoli Chen; En Li; Feifei Song; Nicolas Guimond; Jiean Chen; Yong Huang

doi:10.1055/a-2005-5372

Synlett, Table of Contents

Synlett 2023; 34(09): 1042-1048
DOI: 10.1055/a-2005-5372

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Addition of Alcohols onto Electron-Deficient Heteroarenium Salts: A Reversible Covalent Bonding Process under Basic Conditions

Baoli Chen‡

^aState Key Laboratory of Chemical Oncogenomics, Peking University Shenzhen Graduate School, Shenzhen, 518055, P. R. of China

,

En Li‡

^cPingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen, 518055, P. R. of China

,

Feifei Song

^aState Key Laboratory of Chemical Oncogenomics, Peking University Shenzhen Graduate School, Shenzhen, 518055, P. R. of China

,

Nicolas Guimond

^dProcess Research, Bayer AG Crop Science, 40789 Monheim, Germany

,

Jiean Chen ∗

^aState Key Laboratory of Chemical Oncogenomics, Peking University Shenzhen Graduate School, Shenzhen, 518055, P. R. of China

^cPingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen, 518055, P. R. of China

,

Yong Huang∗

^bDepartment of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR, P. R. of China

› Author Affiliations

Abstract

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Abstract

The reversible addition of benzyl alcohol onto heteroarenium salts under basic conditions was studied. Fine-tuning of the nature of the arenium and substituents allowed the discovery of a range of pyrimidinium substrates that can undergo C6-selective alcohol addition. Crossover experiments were also performed to confirm the addition-elimination equilibrium under basic conditions.

Keywords

heteroarenium salts - alcohols - reversible addition - basic conditions

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References

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12 Synthesis of Compound 3a–z; General Procedure: Pyridinium salt (0.05 mmol), alcohol (1.0 equiv), base (2.0 equiv) and 4Å molecule sieves (100 mg) in CD₃CN (0.5 mL) were stirred for 1 hour under argon in room temperature. Yield was determined by ¹H NMR analysis of the crude mixture with 1,4-dinitrobenzene (0.5 equiv) as internal standard. 6-(Benzyloxy)-1-methyl-1,6-dihydropyrimidine (3a) Yield: 23%. ¹H NMR (400 MHz, CD₃CN): δ = 7.33–7.29 (m, 5 H), 6.79 (d, J = 7.0 Hz, 1 H), 5.61 (d, J = 4.3 Hz, 1 H), 5.19 (ddd, J = 7.0, 4.4, 1.2 Hz, 1 H), 4.33 (d, J = 11.4 Hz, 1 H), 4.12 (d, J = 11.4 Hz, 1 H), 3.04 (s, 3 H).

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