Pentafluorophenyl Esters: Highly Chemoselective Ketyl Precursors for the Synthesis of α,α-Dideuterio Alcohols Using SmI₂ and D₂O as a Deuterium Source

Hengzhao Li, Yuxia Hou, Chengwei Liu, Zemin Lai, Lei Ning, Roman Szostak, Michal Szostak* and Jie An*

*Rutgers University, 73 Warren Street, Newark, New Jersey 07102, United States; College of Science, China Agricultural University, Beijing 100193, China, Email: michal.szostakrutgers.edu, jie_ancau.edu.cn

H. Li, Y. Hou, C. Liu, Z. Lai, L. Ning, R. Szostak, M. Szostak, J. An, Org. Lett., 2020, 22, 1249-1253.

DOI: 10.1021/acs.orglett.9b04383

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Abstract

The use of pentafluorophenyl esters as ketyl radical precursors, SmI₂ as a mild reducing agent, and D₂O as the deuterium source enables a highly chemoselective synthesis of α,α-dideuterio alcohols with exquisite incorporation of deuterium. This system tolerates a variety of functional groups.

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General Procedure for the Reductive Deuteration of Pentafluorophenyl Esters by SmI₂-D₂O

To a solution of samarium (II) iodide (0.100 M in THF; 10.0 mL, 1.00 mmol, 5.00 equiv), was added deuterium oxide (300 mg, 15.0 mmol, 75.0 equiv). A characteristic burgundy red color of SmI₂-D₂O complex was observed. A solution of pentafluorophenyl ester (0.200 mmol, 1.00 equiv) in THF (1.0 mL) was then added under Ar at room temperature and stirred vigorously. After 15 min, excess SmI₂ was oxidized by bubbling air through the reaction mixture. The reaction mixture was diluted with EtOAc (10 mL) and HCl (5 mL, 1.0 M, aq). The aqueous layer was extracted with EtOAc (3 × 10 mL), organic layers were combined, washed with Na₂S₂O₃ (2 × 5 mL, sat., aq), dried over Na₂SO₄, filtered and concentrated. The crude product was purified by flash chromatography (silica, 0-25% EtOAc/Hexane). The sample was analyzed by ¹H NMR (CDCl₃, 300 MHz) to obtain the deuterium incorporation.

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Reductive Deuteration of Aromatic Esters for the Synthesis of α,α-Dideuterio Benzyl Alcohols Using D₂O as Deuterium Source

S. Luo, C. Weng, Y. Ding, C. Ling, M. Szostak, X. Ma, J. An, Synlett, 2021, 32, 51-56.

Highly Chemoselective Reduction of Amides (Primary, Secondary, Tertiary) to Alcohols using SmI₂/Amine/H₂O under Mild Conditions

M. Szostak, M. Spain, A. J. Eberhard, D. J. Procter, J. Am. Chem. Soc., 2014, 136, 2268-2271.

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Key Words

reduction of esters, samarium diiodide

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ID: J54-Y2020