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Enantioselective Synthesis of (−)-10-Hydroxyacutuminine

Grünenfelder, Denise C. and Navarro, Raul and Wang, Haoxuan and Fastuca, Nicholas J. and Butler, John R. and Reisman, Sarah E. (2022) Enantioselective Synthesis of (−)-10-Hydroxyacutuminine. Angewandte Chemie International Edition, 61 (16). Art. No. e202117480. ISSN 1433-7851. doi:10.1002/anie.202117480. https://resolver.caltech.edu/CaltechAUTHORS:20220204-679540000

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1002/anie.202117480DOIArticle
ORCID:
AuthorORCID
Wang, Haoxuan0000-0002-8663-3073
Fastuca, Nicholas J.0000-0003-4081-6031
Reisman, Sarah E.0000-0001-8244-9300
Alternate Title:Enantioselective Synthesis of (-)-C10-Hydroxyacutuminine
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.
Funders:
Funding AgencyGrant Number
NSF Graduate Research FellowshipDGE-1144469
NSFCHE-1057143
NSFCHE-1800536
Subject Keywords:Acutumine Alkaloids; Deoxychlorination; Dieckmann Cyclization; Total Synthesis; [2+2] Cycloaddition
Issue or Number:16
DOI:10.1002/anie.202117480
Record Number:CaltechAUTHORS:20220204-679540000
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20220204-679540000
Official Citation:Enantioselective Synthesis of (−)-10-Hydroxyacutuminine. D. C. Grünenfelder, R. Navarro, H. Wang, N. J. Fastuca, J. R. Butler, S. E. Reisman, Angew. Chem. Int. Ed. 2022, 61, e202117480; Angew. Chem. 2022, 134, e202117480.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:113284
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:07 Feb 2022 20:24
Last Modified:06 Apr 2022 21:37

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