Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams

Handle URI:
http://hdl.handle.net/10754/598160
Title:
Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams
Authors:
Behenna, Douglas C.; Liu, Yiyang; Yurino, Taiga; Kim, Jimin; White, David E.; Virgil, Scott C.; Stoltz, Brian M.
Abstract:
The enantioselective synthesis of nitrogen-containing heterocycles (N-heterocycles) represents a substantial chemical research effort and resonates across numerous disciplines, including the total synthesis of natural products and medicinal chemistry. In this Article, we describe the highly enantioselective palladium-catalysed decarboxylative allylic alkylation of readily available lactams to form 3,3-disubstituted pyrrolidinones, piperidinones, caprolactams and structurally related lactams. Given the prevalence of quaternary N-heterocycles in biologically active alkaloids and pharmaceutical agents, we envisage that our method will provide a synthetic entry into the de novo asymmetric synthesis of such structures. As an entry for these investigations we demonstrate how the described catalysis affords enantiopure quaternary lactams that intercept synthetic intermediates previously used in the synthesis of the Aspidosperma alkaloids quebrachamine and rhazinilam, but that were previously only available by chiral auxiliary approaches or as racemic mixtures. © 2012 Macmillan Publishers Limited. All rights reserved.
Citation:
Behenna DC, Liu Y, Yurino T, Kim J, White DE, et al. (2011) Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams. Nature Chem 4: 130–133. Available: http://dx.doi.org/10.1038/NCHEM.1222.
Publisher:
Springer Nature
Journal:
Nature Chemistry
KAUST Grant Number:
KUS-11-006-02
Issue Date:
18-Dec-2011
DOI:
10.1038/NCHEM.1222
PubMed ID:
22270628
Type:
Article
ISSN:
1755-4330; 1755-4349
Sponsors:
This publication is based on work supported by award from the King Abdullah University of Science and Technology (KAUST; no. KUS-11-006-02). The authors thank NIH-NIGMS (R01GM080269-01 and a postdoctoral fellowship to D.E.W.), the Gordon and Betty Moore Foundation, Amgen, Abbott, Boehringer Ingelheim and Caltech for financial support. T.Y. acknowledges the Japan Society for the Promotion of Science for a predoctoral fellowship.
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Publications Acknowledging KAUST Support

Full metadata record

DC FieldValue Language
dc.contributor.authorBehenna, Douglas C.en
dc.contributor.authorLiu, Yiyangen
dc.contributor.authorYurino, Taigaen
dc.contributor.authorKim, Jiminen
dc.contributor.authorWhite, David E.en
dc.contributor.authorVirgil, Scott C.en
dc.contributor.authorStoltz, Brian M.en
dc.date.accessioned2016-02-25T13:13:50Zen
dc.date.available2016-02-25T13:13:50Zen
dc.date.issued2011-12-18en
dc.identifier.citationBehenna DC, Liu Y, Yurino T, Kim J, White DE, et al. (2011) Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams. Nature Chem 4: 130–133. Available: http://dx.doi.org/10.1038/NCHEM.1222.en
dc.identifier.issn1755-4330en
dc.identifier.issn1755-4349en
dc.identifier.pmid22270628en
dc.identifier.doi10.1038/NCHEM.1222en
dc.identifier.urihttp://hdl.handle.net/10754/598160en
dc.description.abstractThe enantioselective synthesis of nitrogen-containing heterocycles (N-heterocycles) represents a substantial chemical research effort and resonates across numerous disciplines, including the total synthesis of natural products and medicinal chemistry. In this Article, we describe the highly enantioselective palladium-catalysed decarboxylative allylic alkylation of readily available lactams to form 3,3-disubstituted pyrrolidinones, piperidinones, caprolactams and structurally related lactams. Given the prevalence of quaternary N-heterocycles in biologically active alkaloids and pharmaceutical agents, we envisage that our method will provide a synthetic entry into the de novo asymmetric synthesis of such structures. As an entry for these investigations we demonstrate how the described catalysis affords enantiopure quaternary lactams that intercept synthetic intermediates previously used in the synthesis of the Aspidosperma alkaloids quebrachamine and rhazinilam, but that were previously only available by chiral auxiliary approaches or as racemic mixtures. © 2012 Macmillan Publishers Limited. All rights reserved.en
dc.description.sponsorshipThis publication is based on work supported by award from the King Abdullah University of Science and Technology (KAUST; no. KUS-11-006-02). The authors thank NIH-NIGMS (R01GM080269-01 and a postdoctoral fellowship to D.E.W.), the Gordon and Betty Moore Foundation, Amgen, Abbott, Boehringer Ingelheim and Caltech for financial support. T.Y. acknowledges the Japan Society for the Promotion of Science for a predoctoral fellowship.en
dc.publisherSpringer Natureen
dc.titleEnantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactamsen
dc.typeArticleen
dc.identifier.journalNature Chemistryen
dc.contributor.institutionCalifornia Institute of Technology, Pasadena, United Statesen
kaust.grant.numberKUS-11-006-02en

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