Palladium-catalyzed asymmetric alkylation in the synthesis of cyclopentanoid and cycloheptanoid core structures bearing all-carbon quaternary stereocenters

Allen Y. Hong, Nathan B. Bennett, Michael R. Krout, Thomas Jensen, Andrew M. Harned, Brian M. Stoltz

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


General catalytic asymmetric routes toward cyclopentanoid and cycloheptanoid core structures embedded in numerous natural products have been developed. The central stereoselective transformation in our divergent strategies is the enantioselective decarboxylative alkylation of seven-membered β-ketoesters to form α-quaternary vinylogous esters. Recognition of the unusual reactivity of β-hydroxyketones resulting from the addition of hydride or organometallic reagents enabled divergent access to γ-quaternary acylcyclopentenes through a ring contraction pathway or γ-quaternary cycloheptenones through a carbonyl transposition pathway. Synthetic applications of these compounds were explored through the preparation of mono-, bi-, and tricyclic derivatives that can serve as valuable intermediates for the total synthesis of complex natural products. This work complements our previous work with cyclohexanoid systems.
Original languageEnglish (US)
Pages (from-to)10234-10248
Number of pages15
Issue number52
StatePublished - Dec 2011
Externally publishedYes

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): KUS-11-006-02
Acknowledgements: This publication is based on work supported by Award No. KUS-11-006-02, made by King Abdullah University of Science and Technology (KAUST). The authors wish to thank NIH-NIGMS (R01M080269-01), Amgen, Abbott, Boehringer Ingelheim, and Caltech for financial support. A.Y.H. thanks Roche for an Excellence in Chemistry Award and Abbott for an Abbott Scholars Symposium Award. M.R.K. acknowledges Eli Lilly for a predoctoral fellowship. T.J. thanks the Danish Council for Independent Research/Natural Sciences for a postdoctoral fellowship. Materia, Inc. is gratefully acknowledged for the donation of metathesis catalysts. Lawrence Henling and Dr. Michael Day are acknowledged for X-ray crystallographic structure determination. The Bruker KAPPA APEXII X-ray diffractometer used in this study was purchased via an NSF CRIF:MU award to Caltech (CHE-0639094). Prof. Sarah Reisman, Dr. Scott Virgil, Dr. Christopher Henry, and Dr. Nathaniel Sherden contributed with helpful discussions. Dr. David VanderVelde and Dr. Scott Ross are acknowledged for NMR assistance. The Varian 400 MR instrument used in this study was purchased via an NIH award to Caltech (NIH RR027690). Dr. Mona Shahgholi and Naseem Torian are acknowledged for high-resolution mass spectrometry assistance.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.


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