CaltechAUTHORS
Published April 11, 2022 | Version Accepted Version + Supplemental Material
Journal Article Open

Enantioselective Synthesis of (−)-10-Hydroxyacutuminine

Creators

  • 1. ROR icon California Institute of Technology

Abstract

An enantioselective synthesis of (−)-10-hydroxyacutuminine is reported. Central to our strategy is a photochemical [2+2] cycloaddition that forges two of the quaternary stereocenters present in the acutumine alkaloids. A subsequent retro-aldol/Dieckmann sequence furnishes the spirocyclic cyclopentenone. Efforts to chlorinate the acutumine scaffold at C10 under heterolytic or radical deoxychlorination conditions led to the synthesis of an unexpected cyclopropane-containing pentacycle.

Additional Information

© 2022 Wiley-VCH. Issue Online: 03 April 2022; Version of Record online: 23 February 2022; Accepted manuscript online: 02 February 2022; Manuscript received: 22 December 2021. We are grateful to Dr. Scott Virgil and the Caltech Center for Catalysis and Chemical Synthesis for access to analytical equipment, and Dr. David VanderVelde for assistance with NMR structural analysis. Dr. Lawrence M. Henling is acknowledged for the acquisition, and Dr. Michael K. Takase and Dr. Julie L. Hofstra for solving the X-ray crystal structure of 34. We also thank Dr. Nicholas G. W. Cowper, Dr. Elliot P. Farney, and Dr. Jordan C. Beck for helpful discussions, and Yujia Tao for the synthesis and characterization of ketone 24, as well as assistance in the chlorination trials of cyclopropane 35. Financial support was provided by the National Science Foundation (graduate research fellowship to D. C. G., Grant No. DGE-1144469, and CAREER-1057143, CHE-1800536 to S. E. R.) and is gratefully acknowledged. The authors declare no conflict of interest. Data Availability Statement: The data that support the findings of this study are available in the supplementary material of this article.

Attached Files

Accepted Version - Angewandte_Chemie_Intl_Edit_-_2022_-_Gr_nenfelder_-_Enantioselective_Synthesis_of____‐C10‐Hydroxyacutuminine.pdf

Supplemental Material - anie202117480-sup-0001-misc_information.pdf

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Angewandte_Chemie_Intl_Edit_-_2022_-_Gr_nenfelder_-_Enantioselective_Synthesis_of____‐C10‐Hydroxyacutuminine.pdf

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Additional details

Additional titles

Alternative title
Enantioselective Synthesis of (-)-C10-Hydroxyacutuminine

Identifiers

Eprint ID
113284
DOI
10.1002/anie.202117480
Resolver ID
CaltechAUTHORS:20220204-679540000

Related works

Describes
10.1002/anie.202117480 (DOI)

Funding

NSF Graduate Research Fellowship
DGE-1144469
NSF
CHE-1057143
NSF
CHE-1800536

Dates

Created
2022-02-07
Created from EPrint's datestamp field
Updated
2022-04-06
Created from EPrint's last_modified field