Catalytic Michael/Ring-Closure Reaction of α,β-Unsaturated Pyrazoleamides with Amidomalonates: Asymmetric Synthesis of (−)-Paroxetine

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• 作者：Yu Zhang ; Yuting Liao ; Prof.&ensp ; Dr. Xiaohua Liu ; Qian Yao ; Yuhang Zhou ; Dr. Lili Lin and Prof.&ensp ; Dr. Xiaoming Feng
• 刊名：Chemistry - A European Journal
• 出版年：2016
• 出版时间：October 10, 2016
• 年：2016
• 卷：22
• 期：42
• 页码：15119-15124
• 全文大小：835K
• ISSN：1521-3765

文摘

A highly enantioselective tandem Michael/ring-closure reaction of α,β-unsaturated pyrazoleamides and amidomalonates has been accomplished in the presence of a chiral N,N′-dioxide–Yb(OTf)₃ complex (Tf: trifluoromethanesulfonyl) to give various substituted chiral glutarimides with high yields and diastereo- and enantioselectivities. Moreover, this methodology could be used for gram-scale manipulation and was successfully applied to the synthesis of (−)-paroxetine. Further nonlinear and HRMS studies revealed that the real catalytically active species was a monomeric L-PMe₂–Yb³⁺ complex. A plausible transition state was proposed to explain the origin of the asymmetric induction.