Journal ArticleDOI
Synthesis of Enantiopure trans-3,4-Disubstituted Piperidines. An Enantiodivergent Synthesis of (+)- and (−)-Paroxetine
Mercedes Amat,Joan Bosch,José Hidalgo,Margalida Cantó,Maria Pérez,Núria Llor,Elies Molins,Carles Miravitlles,Modesto Orozco,Javier Luque +9 more
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TLDR
On treatment with lithium alkyl (or aryl) cyanocuprates, these chiral building blocks undergo conjugate addition to give enantiopure trans-3,4-substituted 2-piperidone derivatives in high yield and stereoselectivity.Abstract:
Reaction of (R)-phenylglycinol with methyl 5-oxopentanoate gave either bicyclic lactam cis-1 (the kinetic product) or its isomer trans-1 (under equilibrating conditions) as the major products, which were converted to the corresponding (cis or trans) unsaturated lactams 4 and 5 On treatment with lithium alkyl (or aryl) cyanocuprates, these chiral building blocks undergo conjugate addition to give enantiopure trans-3,4-substituted 2-piperidone derivatives in high yield and stereoselectivity The synthetic potential of this transformation is illustrated by the synthesis of (+)-femoxetine and the two enantiomers of the known antidepressant paroxetineread more
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Recent advances in the synthesis of piperidones and piperidines
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Chiral heterocycles by iminium ion cyclization.
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Organocatalytic Conjugate Addition of Malonates to α,β-Unsaturated Aldehydes: Asymmetric Formal Synthesis of (−)-Paroxetine, Chiral Lactams, and Lactones
TL;DR: Organocatalytic conjugate addition of malonates to alpha, beta-unsaturated aldehydes : Asymmetric formal synthesis of (-)-paroxetine, chiral lactams, and lactones as discussed by the authors.
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Chiral Non-Racemic Bicyclic Lactams. Auxiliary-Based Asymmetric Reactions
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Chiral oxazolopiperidone lactams: versatile intermediates for the enantioselective synthesis of piperidine-containing natural products.
TL;DR: Of particular interest are cyclocondensation reactions with racemic or prochiral delta-oxo (di)acid derivatives in processes involving dynamic kinetic resolution and/or differentiation of enantiotopic or diastereotopic ester groups, as they directly lead to lactams that already incorporate the carbon substituents on the heterocyclic ring.
References
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Paroxetine : a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depressive illness
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Polarization effects in generalized molecular interaction potential: New Hamiltonian for reactivity studies and mixed QM/MM calculations
F. Javier Luque,Modesto Orozco +1 more
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