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Boryl-Dictated Site-Selective Intermolecular Allylic and Propargylic C-H Amination

Yuan Liu, Zhi-Hao Chen, Yin Li, Jiasheng Qian, Qingjiang Li and Honggen Wang*

*School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China, Email: wanghg3mail.sysu.edu.cn

Y. Liu, Z.-H. Chen, Y. Li, J. Qian, Q. Li, H. Wang, J. Am. Chem. Soc., 2022, 144, 14380-14387.

DOI: 10.1021/jacs.2c06117


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Abstract

A boryl-directed intermolecular C-H amination of allyl N-methyliminodiacetyl boronates (B(MIDA)s) and propargylic B(MIDA)s provide α-amino boronates with an exceptionally high level of site-selectivity. A wide variety of highly functionalized secondary and tertiary α-amino boronates are formed in very good yields under mild reaction conditions.

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proposed mechanism

drugs containing the α-aminoboronic acid moiety: Bortezomib, Dup-714, Vaborbactam, Delanzomib



General procedure I:

The allyl MIDA boronate (0.2 mmol, 1.0 equiv), sulfonamides/sulfamates (0.4 mmol, 2.0 equiv) and 1,3-dimethyl-1,3-dihydro-2H-imidazole-2-selenone (IMeSe)(0.05 mmol, 25 mol%) were added to a 15 mL oven-dried pressure tube equipped with a stir bar. Dry DCM (1.0 mL) was added to the tube in gloves box and stirred for 30 seconds. After adding PhI(OAc)2 (1 mmol, 5.0 equiv), the tube was sealed with a thread plug. The solution was stirred at 35C until the allyl boronic ester was used up by TLC monitoring. The solvent was removed in vacuo and the crude product was purified by flash column chromatography on silica with an eluent (PE / EtOAc from 2:1 to 1:5, v/v) to afford the pure product.

General procedure II:

The propargyl MIDA boronates (0.1 mmol, 1.0 equiv), sulfamides (0.2 mmol, 2.0 equiv) and 1,3-dimethyl-1,3-dihydro-2H-imidazole-2-selenone (IMeSe, 1.8 mg, 0.01 mmol) were added to a 15 mL oven-dried pressure tube equipped with a stir bar. Dry DCM (1.0 mL) was added to the tube in gloves box and stirred for 30 seconds. After adding iodobenzene phenylacetic (237 mg, 0.5 mmol, 5.0 equiv), the solution turned yellow and the tube was sealed with a thread plug. The solution was stirred at 40C until the propargyl boronic ester was used up by TLC monitoring. The solvent was removed in vacuo and the crude product was purified by flash column chromatography on silica with an eluent (DCM / EtOAc from 3:1 to 2:1, v/v) to afford the pure product as a white solid.


Key Words

Allylic Amines, Propargylic Amines, α-Aminoboronates, PIDA, hypervalent iodine compounds


ID: J48-Y2022