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. 2025 Jul 1;16(1):5686.
doi: 10.1038/s41467-025-60230-5.

Enantioselective electroreductive alkyne-aldehyde coupling

Xiyang Cao  1 , Yuyang Fu  1 , Yongsheng Tao  1 , Qingquan Lu  2   3
Affiliations

Enantioselective electroreductive alkyne-aldehyde coupling

Xiyang Cao et al. Nat Commun. .

Abstract

Electrocatalytic methods that facilitate the asymmetric reductive coupling of two π-components with complete control over regio-, stereo-, and enantioselectivity remain underexplored. Herein, we report a highly regio- and enantioselective cobaltaelectro-catalyzed alkyne-aldehyde coupling reaction, in which protons and electrons serve as the hydrogen source and reductant, respectively. Earth-abundant cobalt and air-stable (S,S)-2,3-bis(tert-butylmethylphosphino)quinoxaline (QuinoxP*) are used as the catalyst and ligand, respectively. A series of enantioenriched allylic alcohols can be constructed with excellent regio- (>19:1), stereo- (>19:1 E:Z), and enantioselectivity (up to 98% ee).

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Introduction.
a Metal-catalyzed asymmetric alkyne-aldehyde coupling. b Enantioselective electroreductive alkyne-aldehyde coupling (this work).
Fig. 2
Fig. 2. Initial mechanistic studies.
a CV studies of the interaction of [Co(OAc)2/L1] with different proton sources. b Comparison of hydrogen current for [Co(OAc)2/L1] with different proton sources under a constant cathode potential at −1.6 V vs Ag/AgCl. c Effects of proton sources on electroreductive alkyne-aldehyde coupling; For details, see the Supplementary information.
Fig. 3
Fig. 3. Substrate scope of alkynes.
Reaction conditions: alkynes (0.2 mmol), aldehydes (3.0 equiv.), nBu4NBF4 (0.05 M), DMAc (6.0 mL), r.t., 2.5 F/mol, 3 mA, argon. a3.0 mA, 5.0 F/mol. bAldehydes (5.0 equiv.).
Fig. 4
Fig. 4. Substrate scope of aldehydes, natural product derivatives.
Reaction conditions: alkynes (0.2 mmol), aldehydes (3.0 equiv.), nBu4NBF4 (0.05 M), DMAc (6.0 mL), r.t., 2.5 F/mol, 3 mA, argon.
Fig. 5
Fig. 5. Mechanistic studies.
a Electrode potential over the course of electrolysis; (b) CVs of substrates; (c) Yield monitoring during electrolysis; (d) Ee of product 28 under different current conditions; (e) Nonlinear effect study; (f) X-ray crystal structure of Co-complex I.
Fig. 6
Fig. 6. Control experiments.
a Co-complex I was employed as the catalyst. b Radical trapping experiments. c Reaction with allene. d Deuterium scrambling experiment.
Fig. 7
Fig. 7. Proposed mechanism.
The possible mechanism for electroreductive alkyne-aldehyde coupling.
See this image and copyright information in PMC

References

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