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Synthesis 2019; 51(21): 3964-3972
DOI: 10.1055/s-0039-1690521
paper
© Georg Thieme Verlag Stuttgart · New York

A One-Pot Intramolecular Tandem Michael–Aldol Annulation Reaction for the Synthesis of Chiral Pentacyclic Terpenes

Jianyu Lu
a   Department of Chemistry, Kansas State University, Manhattan, KS 66506, USA   Email: duy@ksu.edu
,
Serkan Koldas
a   Department of Chemistry, Kansas State University, Manhattan, KS 66506, USA   Email: duy@ksu.edu
,
Huafang Fan
a   Department of Chemistry, Kansas State University, Manhattan, KS 66506, USA   Email: duy@ksu.edu
,
John Desper
a   Department of Chemistry, Kansas State University, Manhattan, KS 66506, USA   Email: duy@ksu.edu
,
Victor W. Day
b   Department of Chemistry, University of Kansas, Lawrence, KS 66045, USA
,
Duy H. Hua∗
a   Department of Chemistry, Kansas State University, Manhattan, KS 66506, USA   Email: duy@ksu.edu
› Author AffiliationsThe research reported in this publication was supported in part by the American Heart Association, Heartland Affiliate (0750115Z) and the National Science Foundation, Division of Chemistry (CHE-1662705). This material was based upon work in part supported by the National Science Foundation, Division of Chemistry for the purchase of an NMR spectrometer (1826982 to D.H.H.) and for the purchase of an X-ray diffractometer and the software used in this study (CHE-0923449 to V.W.D.).
Further Information

Publication History

Received: 12 June 2019

Accepted after revision: 19 July 2019

Publication Date:
07 August 2019 (online)

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Abstract

A chiral tricyclic terpene possessing a 6,6,6-tricyclic framework and a 3,3-dimethyl-7-oxooctylidenyl side chain undergoes a double ring-closing reaction to give two chiral pentacyclic terpenes in a ratio of 4:3 via an intramolecular Michael addition followed by aldol condensation under basic conditions. Three new stereogenic centers are introduced in the initial Michael annulation reaction. Stereoselective installation of an ethoxycarbonyl group at C17 of the two pentacyclic terpenes separately gives the corresponding highly functionalized pentacyclic terpenoids with seven stereogenic centers. The structures and stereochemistry of key intermediates and products are established through X-ray crystallographic analysis. A mechanism is proposed for explaining the stereochemistry in the Michael annulation reaction.

Key words

1,4-addition - chiral synthesis - double ring-closing - pentacyclic triterpenes - tandem Michael–aldol annulation

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0039-1690521.
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