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

Behenna, Douglas C. and Liu, Yiyang and Yurino, Taiga and Kim, Jimin and White, David E. and Virgil, Scott C. and Stoltz, Brian M. (2012) Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams. Nature Chemistry, 4 (2). pp. 130-133. ISSN 1755-4330. PMCID PMC3266627. https://resolver.caltech.edu/CaltechAUTHORS:20120126-101327960

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1038/nchem.1222DOIArticle
http://www.nature.com/nchem/journal/v4/n2/full/nchem.1222.htmlPublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266627/PubMed CentralArticle
http://rdcu.be/omTPPublisherFree ReadCube access
ORCID:
AuthorORCID
Virgil, Scott C.0000-0001-8586-5641
Stoltz, Brian M.0000-0001-9837-1528
Additional Information:© 2012 Macmillan Publishers Limited. Received 13 October 2011; Accepted 07 November 2011; Published online 18 December 2011. 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. Author contributions: D.C.B., Y.L., T.Y. and J.K. planned and carried out the experimental work. D.C.B., T.Y., D.E.W. and S.C.V. took part in the initial reaction development and screening experiments. B.M.S. conceived, initiated and directed the project and wrote the manuscript. All authors commented on the manuscript.
Funders:
Funding AgencyGrant Number
King Abdullah University of Science and Technology (KAUST)KUS-11-006-02
NIHR01GM080269-01
NIH Postdoctoral FellowshipUNSPECIFIED
Gordon and Betty Moore FoundationUNSPECIFIED
AmgenUNSPECIFIED
AbbottUNSPECIFIED
Boehringer IngelheimUNSPECIFIED
CaltechUNSPECIFIED
Japan Society for the Promotion of Science (JSPS)UNSPECIFIED
Subject Keywords:Organic chemistry; Synthesis
Issue or Number:2
PubMed Central ID:PMC3266627
Record Number:CaltechAUTHORS:20120126-101327960
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20120126-101327960
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:28980
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:21 Mar 2012 21:07
Last Modified:09 Mar 2020 13:19

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