Issue 20, 2025

Carbene-catalyzed enantioselective construction of a quasi-symmetrical spirocyclic hydroquinone with a minor chiral distinction

Abstract

Constructing a nearly symmetrical chiral center with tiny chiral differences is a challenging task in asymmetric synthesis. The natural antibiotic fredericamycin A (FDM-A), a representative example, has a unique structure with a quasi-symmetrical spirocyclic hydroquinone and remains difficult to chemically synthesize. Herein we developed an N-heterocyclic carbene–catalyzed enantioselective hydroquinone formation reaction with desymmetrization of spirocyclic cyclopentene-1,3-diones to construct these challenging structures. Using our method, the asymmetric synthesis of FDM-A (previously requiring a 26-step or 32-step synthesis) was shortened to 11 steps. Several analogs of FDM-A were also readily made. Moreover, a more challenging all-carbon quaternary chiral center with minimal differences (H vs. D) in a remote position (6 atoms away from the chiral center) was also constructed to investigate the performance of the extremely weakly chiral small molecule.

Graphical abstract: Carbene-catalyzed enantioselective construction of a quasi-symmetrical spirocyclic hydroquinone with a minor chiral distinction

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Article information

Article type
Edge Article
Submitted
28 Feb 2025
Accepted
10 Apr 2025
First published
15 Apr 2025
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2025,16, 8940-8945

Carbene-catalyzed enantioselective construction of a quasi-symmetrical spirocyclic hydroquinone with a minor chiral distinction

P. Ren, Q. Zhao, Y. R. Chi and T. Zhu, Chem. Sci., 2025, 16, 8940 DOI: 10.1039/D5SC01605C

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