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. 2022 Feb 11;24(5):1228-1231.
doi: 10.1021/acs.orglett.2c00020. Epub 2022 Jan 31.

Cu(I)-Catalyzed Alkynylation of Quinolones

Aitor Maestro  1 , Sebastien Lemaire  2 , Syuzanna R Harutyunyan  1
Affiliations

Cu(I)-Catalyzed Alkynylation of Quinolones

Aitor Maestro et al. Org Lett. .

Abstract

Herein we report the first alkynylation of quinolones with terminal alkynes under mild reaction conditions. The reaction is catalyzed by Cu(I) salts in the presence of a Lewis acid, which is essential for the reactivity of the system. The enantioselective version of this transformation has also been explored, and the methodology has been applied in the synthesis of the enantioenriched tetrahydroquinoline alkaloid cuspareine.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Relevant quinolones and their derivatives.
Scheme 1
Scheme 1. Functionalization of 4-Quinolones: (a) Arylation, (b) Alkylation, and (c) Alkynylation (This Work)
Scheme 2
Scheme 2. Scope of the Reaction
Reaction conditions: quinolone 1 (0.1 mmol), CuI (10 mol %), toluene (1 mL), alkyne 2 (1.3 equiv), DIPEA (1.6 equiv), TBDMSOTf (1.2 equiv).
Scheme 3
Scheme 3. Enantioselective Alkynylation of Quinolones
Reaction conditions: quinolone 1a (0.1 mmol), CuI (10 mol %), I (11 mol %), toluene (1 mL), alkyne 2 (1.3 equiv), DIPEA (1.6 equiv), TBDMSOTf (1.2 equiv). ee values were determined by chiral high-performance liquid chromatography (HPLC) or supercritical fluid chromatography (SFC).
Scheme 4
Scheme 4. Scaling Up and Synthetic Applications of Quinolone Derivatives 3
See this image and copyright information in PMC

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