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New Catalytic Radical Process Involving 1,4-Hydrogen Atom Abstraction: Asymmetric Construction of Cyclobutanones

Jingjing Xie, Pan Xu, Yiling Zhu, Jingyi Wang, Wan-Chen Cindy Lee and X. Peter Zhang*

*Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, United States, Email: peter.zhangbc.edu

J. Xie, P. Xu, Y. Zhu, J. Wang, W.-C. C. Lee, X. P. Zhang, J. Am. Chem. Soc., 2021, 143, 11337-11344.

DOI: 10.1021/jacs.1c04968


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Abstract

A catalytic radical process enables an asymmetric 1,4-C-H alkylation of diazoketones for stereoselective construction of cyclobutanone structures. The key to success is the optimization of the Co(II)-based metalloradical catalyst through judicious modulation of a D2-symmetric chiral amidoporphyrin ligand to adopt proper steric, electronic, and chiral environments.

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proposed mechanism

[Co(3,5-DiOMe-Hu(C6)Phyrin)]



General Procedure for Enantioselective Radical Cyclization

An oven-dried Schlenk tube was charged with diazo compound (0.1 mmol) and Co complex (2 mol %). The Schlenk tube was then evacuated and backfilled with nitrogen for 3 times. The Teflon screw cap was replaced with a rubber septum, tert-butyl methyl ether (TBME) (0.5 mL) was added via a gastight syringe. The tube was then purged with nitrogen for 30 s and the rubber septum was replaced with a Teflon screw cap. The mixture was then stirred at 40 C. After 12 h, the reaction mixture was concentrated and purified by flash chromatography (hexanes/EtOAc 20:1, 8:1, or 3:1). The fractions containing product were collected and concentrated by rotary evaporation to afford the desired compound.


Key Words

Cyclobutanones, Hydrogen-Atom Abstraction, Metalloradical Catalysis, Radical Reaction, C-H Alkylation


ID: J48-Y2021