511284-07-4Relevant academic research and scientific papers
Catalytic Michael/Ring-Closure Reaction of α,β-Unsaturated Pyrazoleamides with Amidomalonates: Asymmetric Synthesis of (?)-Paroxetine
Zhang, Yu,Liao, Yuting,Liu, Xiaohua,Yao, Qian,Zhou, Yuhang,Lin, Lili,Feng, Xiaoming
supporting information, p. 15119 - 15124 (2016/10/11)
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)3complex (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.
Application of the chiral base desymmetrisation of imides to the synthesis of the alkaloid jamtine and the antidepressant paroxetine
Gill, Christopher D.,Greenhalgh, Daniel A.,Simpkins, Nigel S.
, p. 9213 - 9230 (2007/10/03)
The synthesis of the alkaloid jamtine and the antidepressant paroxetine have been addressed by a strategy involving asymmetric desymmetrisation of prochiral imides by a chiral lithium amide base. A short reaction sequence, starting with a cyclohexane fused succinimide, led to the structures originally reported for the alkaloid jamtine and its derived N-oxide. The structures synthesised are shown not to correspond with those originally reported. A second sequence involves desymmetrisation of a 4-arylglutarimide, and provides a short enantioselective synthesis of the drug substance paroxetine.
A novel chiral base mediated glutarimide desymmetrisation: Application to the asymmetric synthesis of (-)-paroxetine
Greenhalgh, Daniel A.,Simpkins, Nigel S.
, p. 2074 - 2076 (2007/10/03)
The asymmetric desymmetrisation of certain 4-aryl substituted glutarimides has been accomplished with high levels of selectivity (up to 97% ee) by enolisation with a chiral bis-lithium amide base. The selectivity of the reaction is shown to be the result of asymmetric enolisation, followed by a kinetic resolution. One of the chiral imides synthesised was converted into the selective seratonin reuptake inhibitor (-)-paroxetine.
