Enantioselective Desymmetrization of 1,4-Dihydropyridines by Oxidative NHC Catalysis

Graziano Di Carmine; Daniele Ragno; Arianna Brandolese; Olga Bortolini; Daniel Pecorari; Federica Sabuzi; Andrea Mazzanti; Alessandro Massi

doi:10.1002/chem.201901243

Enantioselective Desymmetrization of 1,4-Dihydropyridines by Oxidative NHC Catalysis

Graziano Di Carmine, Daniele Ragno, Arianna Brandolese, Olga Bortolini, Daniel Pecorari, Federica Sabuzi, Andrea Mazzanti^*, Alessandro Massi

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

Abstract

The unprecedented desymmetrization of prochiral dialdehydes catalyzed by N-heterocyclic carbenes under oxidative conditions was applied to the highly enantioselective synthesis of 1,4-dihydropyridines (DHPs) starting from 3,5-dicarbaldehyde substrates. Synthetic elaboration of the resulting 5-formyl-1,4-DHP-3-carboxylates allowed for access to the class of pharmaceutically relevant 1,4-DHP-3,5-dicarboxylates (Hantzsch esters). DFT calculations suggested that the enantioselectivity of the process is determined by the transition state involving the oxidation of the Breslow intermediate by the external quinone oxidant.

Original language	English
Pages (from-to)	7469-7474
Number of pages	6
Journal	Chemistry - A European Journal
Volume	25
Issue number	31
DOIs	https://doi.org/10.1002/chem.201901243
Publication status	Published - 4 Jun 2019

Bibliographical note

Publisher Copyright:
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Keywords

carbenes
density functional calculations
desymmetrization
dihydropyridines
organocatalysis

ASJC Scopus subject areas

Catalysis
Organic Chemistry

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10.1002/chem.201901243

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title = "Enantioselective Desymmetrization of 1,4-Dihydropyridines by Oxidative NHC Catalysis",

abstract = "The unprecedented desymmetrization of prochiral dialdehydes catalyzed by N-heterocyclic carbenes under oxidative conditions was applied to the highly enantioselective synthesis of 1,4-dihydropyridines (DHPs) starting from 3,5-dicarbaldehyde substrates. Synthetic elaboration of the resulting 5-formyl-1,4-DHP-3-carboxylates allowed for access to the class of pharmaceutically relevant 1,4-DHP-3,5-dicarboxylates (Hantzsch esters). DFT calculations suggested that the enantioselectivity of the process is determined by the transition state involving the oxidation of the Breslow intermediate by the external quinone oxidant.",

keywords = "carbenes, density functional calculations, desymmetrization, dihydropyridines, organocatalysis",

author = "{Di Carmine}, Graziano and Daniele Ragno and Arianna Brandolese and Olga Bortolini and Daniel Pecorari and Federica Sabuzi and Andrea Mazzanti and Alessandro Massi",

note = "Publisher Copyright: {\textcopyright} 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim",

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doi = "10.1002/chem.201901243",

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AU - Di Carmine, Graziano

AU - Ragno, Daniele

AU - Brandolese, Arianna

AU - Bortolini, Olga

AU - Pecorari, Daniel

AU - Sabuzi, Federica

AU - Mazzanti, Andrea

AU - Massi, Alessandro

PY - 2019/6/4

Y1 - 2019/6/4

N2 - The unprecedented desymmetrization of prochiral dialdehydes catalyzed by N-heterocyclic carbenes under oxidative conditions was applied to the highly enantioselective synthesis of 1,4-dihydropyridines (DHPs) starting from 3,5-dicarbaldehyde substrates. Synthetic elaboration of the resulting 5-formyl-1,4-DHP-3-carboxylates allowed for access to the class of pharmaceutically relevant 1,4-DHP-3,5-dicarboxylates (Hantzsch esters). DFT calculations suggested that the enantioselectivity of the process is determined by the transition state involving the oxidation of the Breslow intermediate by the external quinone oxidant.

AB - The unprecedented desymmetrization of prochiral dialdehydes catalyzed by N-heterocyclic carbenes under oxidative conditions was applied to the highly enantioselective synthesis of 1,4-dihydropyridines (DHPs) starting from 3,5-dicarbaldehyde substrates. Synthetic elaboration of the resulting 5-formyl-1,4-DHP-3-carboxylates allowed for access to the class of pharmaceutically relevant 1,4-DHP-3,5-dicarboxylates (Hantzsch esters). DFT calculations suggested that the enantioselectivity of the process is determined by the transition state involving the oxidation of the Breslow intermediate by the external quinone oxidant.

KW - carbenes

KW - density functional calculations

KW - desymmetrization

KW - dihydropyridines

KW - organocatalysis

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JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

IS - 31

ER -

Enantioselective Desymmetrization of 1,4-Dihydropyridines by Oxidative NHC Catalysis

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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