Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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).

PubMed Disclaimer

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

    1. Gil, A., Albericio, F. & Álvarez, M. Role of the Nozaki–Hiyama–Takai–Kishi reaction in the synthesis of natural products. Chem. Rev.117, 8420–8446 (2017). - PubMed
    1. Butt, N. A. & Zhang, W. Transition metal-catalyzed allylic substitution reactions with unactivated allylic substrates. Chem. Soc. Rev.44, 7929–7967 (2015). - PubMed
    1. Godleski, S. A. in Comprehensive Organic Synthesis (eds Trost, Barry M. & Fleming, Ian) 585–661 (Pergamon, 1991).
    1. Lipshutz, B. H. & Sengupta, S. in Organic Reactions John Wiley & Sons, Inc. 135–631.
    1. Overman, L. E. Charge as a key component in reaction design. the invention of cationic cyclization reactions of importance in synthesis. Acc. Chem. Res.25, 352–359 (1992).

LinkOut - more resources