Hydroalkylation of Alkynes: Functionalization of the Alkenyl Copper Intermediate Through Single Electron Transfer Chemistry

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2021 May 18

PMID 34004114

Citations 9

Authors

Avijit Hazra

Jonathan A Kephart

Alexandra Velian

Gojko Lalic

Affiliations

Soon will be listed here.

Abstract

We have developed a method for the stereoselective coupling of terminal alkynes and α-bromo carbonyls to generate functionalized -alkenes. The coupling is accomplished by merging the closed-shell hydrocupration of alkynes with the open-shell single electron transfer (SET) chemistry of the resulting alkenyl copper intermediate. We demonstrate that the reaction is compatible with various functional groups and can be performed in the presence of aryl bromides, alkyl chlorides, alkyl bromides, esters, nitriles, amides, and a wide range of nitrogen-containing heterocyclic compounds. Mechanistic studies provide evidence for SET oxidation of the alkenyl copper intermediate by an α-bromo ester as the key step that enables the cross coupling.

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References

Barzano G, Cheseaux A, Hu X . Z-Selective Synthesis of Vinyl Boronates through Fe-Catalyzed Alkyl Radical Addition. Org Lett. 2019; 21(2):490-493. DOI: 10.1021/acs.orglett.8b03772. View

Bakhoda A, Okoromoba O, Greene C, Raghibi Boroujeni M, Bertke J, Warren T . Three-Coordinate Copper(II) Alkynyl Complex in C-C Bond Formation: The Sesquicentennial of the Glaser Coupling. J Am Chem Soc. 2020; 142(43):18483-18490. DOI: 10.1021/jacs.0c07137. View

Yu L, Lv L, Qiu Z, Chen Z, Tan Z, Liang Y . Palladium-Catalyzed Formal Hydroalkylation of Aryl-Substituted Alkynes with Hydrazones. Angew Chem Int Ed Engl. 2020; 59(33):14009-14013. DOI: 10.1002/anie.202005132. View

Wille U . Radical cascades initiated by intermolecular radical addition to alkynes and related triple bond systems. Chem Rev. 2012; 113(1):813-53. DOI: 10.1021/cr100359d. View

Cheng L, Mankad N . Heterobimetallic Control of Regioselectivity in Alkyne Hydrostannylation: Divergent Syntheses of α- and ( E) -β -Vinylstannanes via Cooperative Sn-H Bond Activation. J Am Chem Soc. 2019; 141(8):3710-3716. DOI: 10.1021/jacs.9b00068. View

Mailig M, Hazra A, Armstrong M, Lalic G . Catalytic Anti-Markovnikov Hydroallylation of Terminal and Functionalized Internal Alkynes: Synthesis of Skipped Dienes and Trisubstituted Alkenes. J Am Chem Soc. 2017; 139(20):6969-6977. DOI: 10.1021/jacs.7b02104. View

Jordan A, Lalic G, Sadighi J . Coinage Metal Hydrides: Synthesis, Characterization, and Reactivity. Chem Rev. 2016; 116(15):8318-72. DOI: 10.1021/acs.chemrev.6b00366. View

Wiese S, Badiei Y, Gephart R, Mossin S, Varonka M, Melzer M . Catalytic C-H amination with unactivated amines through copper(II) amides. Angew Chem Int Ed Engl. 2010; 49(47):8850-5. DOI: 10.1002/anie.201003676. View

Suess A, Uehling M, Kaminsky W, Lalic G . Mechanism of Copper-Catalyzed Hydroalkylation of Alkynes: An Unexpected Role of Dinuclear Copper Complexes. J Am Chem Soc. 2015; 137(24):7747-53. DOI: 10.1021/jacs.5b03086. View

10.

Till N, Smith R, MacMillan D . Decarboxylative Hydroalkylation of Alkynes. J Am Chem Soc. 2018; 140(17):5701-5705. PMC: 6607893. DOI: 10.1021/jacs.8b02834. View

11.

Cheng L, Mankad N . Cu-Catalyzed Hydrocarbonylative C-C Coupling of Terminal Alkynes with Alkyl Iodides. J Am Chem Soc. 2017; 139(30):10200-10203. DOI: 10.1021/jacs.7b05205. View

12.

Fujihara T, Xu T, Semba K, Terao J, Tsuji Y . Copper-catalyzed hydrocarboxylation of alkynes using carbon dioxide and hydrosilanes. Angew Chem Int Ed Engl. 2010; 50(2):523-7. DOI: 10.1002/anie.201006292. View

13.

Lu X, Liu J, Lu X, Zhang Z, Gong T, Xiao B . 1,1-Disubstituted olefin synthesis via Ni-catalyzed Markovnikov hydroalkylation of alkynes with alkyl halides. Chem Commun (Camb). 2016; 52(30):5324-7. DOI: 10.1039/c6cc00176a. View

14.

Jang W, Lee W, Moon J, Lee J, Yun J . Copper-Catalyzed trans-Hydroboration of Terminal Aryl Alkynes: Stereodivergent Synthesis of Alkenylboron Compounds. Org Lett. 2016; 18(6):1390-3. DOI: 10.1021/acs.orglett.6b00325. View

15.

Shimkin K, Watson D . Recent developments in copper-catalyzed radical alkylations of electron-rich π-systems. Beilstein J Org Chem. 2016; 11:2278-88. PMC: 4685898. DOI: 10.3762/bjoc.11.248. View

16.

Das M, Kaicharla T, Teichert J . Stereoselective Alkyne Hydrohalogenation by Trapping of Transfer Hydrogenation Intermediates. Org Lett. 2018; 20(16):4926-4929. DOI: 10.1021/acs.orglett.8b02055. View

17.

Shi S, Buchwald S . Copper-catalysed selective hydroamination reactions of alkynes. Nat Chem. 2014; 7(1):38-44. PMC: 4270092. DOI: 10.1038/nchem.2131. View

18.

Cheung C, Zhurkin F, Hu X . Z-Selective Olefin Synthesis via Iron-Catalyzed Reductive Coupling of Alkyl Halides with Terminal Arylalkynes. J Am Chem Soc. 2015; 137(15):4932-5. PMC: 4415033. DOI: 10.1021/jacs.5b01784. View

19.

Giri R, Brusoe A, Troshin K, Wang J, Font M, Hartwig J . Mechanism of the Ullmann Biaryl Ether Synthesis Catalyzed by Complexes of Anionic Ligands: Evidence for the Reaction of Iodoarenes with Ligated Anionic Cu Intermediates. J Am Chem Soc. 2017; 140(2):793-806. PMC: 5810543. DOI: 10.1021/jacs.7b11853. View

20.

Uehling M, Rucker R, Lalic G . Catalytic anti-Markovnikov hydrobromination of alkynes. J Am Chem Soc. 2014; 136(24):8799-803. DOI: 10.1021/ja503944n. View