Dynamic Kinetic Resolution Enabled by Intramolecular Benzoin Reaction: Synthetic Applications and Mechanistic Insights.
The highly enantio-, diastereo-, and regioselective dynamic kinetic resolution of β-ketoesters and 1,3-diketones was achieved via a chiral N-heterocyclic carbene catalyzed intramolecular cross-benzoin reaction. A variety of tetralone derivatives bearing two contiguous stereocenters and multiple functionalities were liberated in moderate to excellent yields and with high levels of stereoselectivity (>95% ee and >20:1 dr in most cases). In addition, the excellent regioselectivity control for aryl/alkyl 1,3-diketones, and the superior electronic differentiation of 1,3-diarylketones were highlighted. Moreover, a set of new mechanistic rationale that differs with the currently widely accepted understanding of intramolecular benzoin reactions was established to demonstrate the superior preference of benzoin over aldol transformation: (1) A coexistence of competitive aldol and benzoin reactions was detected, but a retro-aldol-irreversible benzoin process performs a vital role in the generation of predominant benzoin products. (2) The most essential role of an N-electron-withdrawing substituent in triazolium catalysts was revealed to be accelerating the rate of the benzoin transformation, rather than suppressing the aldol process through reducing the inherent basicity of the catalyst.
State Key Laboratory of Structural Chemistry and ‡Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian Institute of Research on the Structure of Matter, University of Chinese Academy of Sciences , Fuzhou, Fujian 350002, PR China.
Guoxiang
G
Zhang
State Key Laboratory of Structural Chemistry and ‡Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian Institute of Research on the Structure of Matter, University of Chinese Academy of Sciences , Fuzhou, Fujian 350002, PR China.
Shuang
S
Yang
State Key Laboratory of Structural Chemistry and ‡Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian Institute of Research on the Structure of Matter, University of Chinese Academy of Sciences , Fuzhou, Fujian 350002, PR China.
Xiaoyan
X
Zhang
State Key Laboratory of Structural Chemistry and ‡Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian Institute of Research on the Structure of Matter, University of Chinese Academy of Sciences , Fuzhou, Fujian 350002, PR China.
Qiqiao
Q
Lin
State Key Laboratory of Structural Chemistry and ‡Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian Institute of Research on the Structure of Matter, University of Chinese Academy of Sciences , Fuzhou, Fujian 350002, PR China.
Deb K
DK
Das
State Key Laboratory of Structural Chemistry and ‡Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian Institute of Research on the Structure of Matter, University of Chinese Academy of Sciences , Fuzhou, Fujian 350002, PR China.
Jian
J
Liu
State Key Laboratory of Structural Chemistry and ‡Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian Institute of Research on the Structure of Matter, University of Chinese Academy of Sciences , Fuzhou, Fujian 350002, PR China.
Xinqiang
X
Fang