Selective C-N Bond Cleavage in Unstrained Pyrrolidines Enabled by Lewis Acid and Photoredox Catalysis

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2024 Oct 23

PMID 39440606

Authors

Kazuhiro Aida

Marina Hirao

Tsuyoshi Saitoh

Takashi Yamamoto

Yasuaki Einaga

Eisuke Ota

Junichiro Yamaguchi

Affiliations

Soon will be listed here.

Abstract

Cleavage of inert C-N bonds in unstrained azacycles such as pyrrolidine remains a formidable challenge in synthetic chemistry. To address this, we introduce an effective strategy for the reductive cleavage of the C-N bond in -benzoyl pyrrolidine, leveraging a combination of Lewis acid and photoredox catalysis. This method involves single-electron transfer to the amide, followed by site-selective cleavage at the C2-N bond. Cyclic voltammetry and NMR studies demonstrated that the Lewis acid is crucial for promoting the single-electron transfer from the photoredox catalyst to the amide carbonyl group. This protocol is widely applicable to various pyrrolidine-containing molecules and enables inert C-N bond cleavage including C-C bond formation via intermolecular radical addition. Furthermore, the current protocol successfully converts pyrrolidines to aziridines, γ-lactones, and tetrahydrofurans, showcasing its potential of the inert C-N bond cleavage for expanding synthetic strategies.

References

Shi S, Szostak R, Szostak M . Proton-coupled electron transfer in the reduction of carbonyls using SmI-HO: implications for the reductive coupling of acyl-type ketyl radicals with SmI-HO. Org Biomol Chem. 2016; 14(38):9151-9157. DOI: 10.1039/c6ob01621a. View

Kim Y, Heo J, Kim D, Chang S, Seo S . Ring-opening functionalizations of unstrained cyclic amines enabled by difluorocarbene transfer. Nat Commun. 2020; 11(1):4761. PMC: 7506026. DOI: 10.1038/s41467-020-18557-8. View

Dongbang S, Doyle A . Ni/Photoredox-Catalyzed C(sp)-C(sp) Coupling between Aziridines and Acetals as Alcohol-Derived Alkyl Radical Precursors. J Am Chem Soc. 2022; 144(43):20067-20077. PMC: 10281197. DOI: 10.1021/jacs.2c09294. View

Honda T, Takahashi R, Namiki H . Syntheses of (+)-cytisine, (-)-kuraramine, (-)-isokuraramine, and (-)-jussiaeiine A. J Org Chem. 2005; 70(2):499-504. DOI: 10.1021/jo048365f. View

Szostak M, Spain M, Procter D . Uncovering the importance of proton donors in TmI2-promoted electron transfer: facile C-N bond cleavage in unactivated amides. Angew Chem Int Ed Engl. 2013; 52(28):7237-41. PMC: 4265963. DOI: 10.1002/anie.201303178. View

Wood D, Guan W, Lin S . Titanium and Cobalt Bimetallic Radical Redox Relay for the Isomerization of -Bz Aziridines to Allylic Amides. Synthesis (Stuttg). 2021; 53(22):4213-4220. PMC: 8579959. DOI: 10.1055/s-0037-1610779. View

Hao W, Wu X, Sun J, Siu J, MacMillan S, Lin S . Radical Redox-Relay Catalysis: Formal [3+2] Cycloaddition of N-Acylaziridines and Alkenes. J Am Chem Soc. 2017; 139(35):12141-12144. DOI: 10.1021/jacs.7b06723. View

Campbell M, Polites V, Patel S, Lipson J, Majhi J, Molander G . Photochemical C-F Activation Enables Defluorinative Alkylation of Trifluoroacetates and -Acetamides. J Am Chem Soc. 2021; 143(47):19648-19654. PMC: 9172939. DOI: 10.1021/jacs.1c11059. View

Laturski A, Gaffen J, Demay-Drouhard P, Caputo C, Baumgartner T . Probing the Impact of Solvent on the Strength of Lewis Acids via Fluorescent Lewis Adducts. Precis Chem. 2023; 1(1):49-56. PMC: 10069026. DOI: 10.1021/prechem.2c00009. View

10.

Do Q, Lee D, Dinh A, Seguin R, Zhang R, Xu L . Development and Application of a Peroxyl Radical Clock Approach for Measuring Both Hydrogen-Atom Transfer and Peroxyl Radical Addition Rate Constants. J Org Chem. 2020; 86(1):153-168. DOI: 10.1021/acs.joc.0c01920. View

11.

Li H, Lai Z, Adijiang A, Zhao H, An J . Selective C-N σ Bond Cleavage in Azetidinyl Amides under Transition Metal-Free Conditions. Molecules. 2019; 24(3). PMC: 6384560. DOI: 10.3390/molecules24030459. View

12.

Zhang W, Lu L, Zhang W, Wang Y, Ware S, Mondragon J . Electrochemically driven cross-electrophile coupling of alkyl halides. Nature. 2022; 604(7905):292-297. PMC: 9016776. DOI: 10.1038/s41586-022-04540-4. View

13.

Kennedy S, Dherange B, Berger K, Levin M . Skeletal editing through direct nitrogen deletion of secondary amines. Nature. 2021; 593(7858):223-227. DOI: 10.1038/s41586-021-03448-9. View

14.

Estrada J, Williams W, Ting S, Doyle A . Role of Electron-Deficient Olefin Ligands in a Ni-Catalyzed Aziridine Cross-Coupling To Generate Quaternary Carbons. J Am Chem Soc. 2020; 142(19):8928-8937. PMC: 7456354. DOI: 10.1021/jacs.0c02237. View

15.

Day J, Teegardin K, Weaver J, Chan J . Advances in Photocatalysis: A Microreview of Visible Light Mediated Ruthenium and Iridium Catalyzed Organic Transformations. Org Process Res Dev. 2016; 20(7):1156-1163. PMC: 4972501. DOI: 10.1021/acs.oprd.6b00101. View

16.

Osberger T, Rogness D, Kohrt J, Stepan A, White M . Oxidative diversification of amino acids and peptides by small-molecule iron catalysis. Nature. 2016; 537(7619):214-219. PMC: 5161617. DOI: 10.1038/nature18941. View

17.

McCallum T, Wu X, Lin S . Recent Advances in Titanium Radical Redox Catalysis. J Org Chem. 2019; 84(22):14369-14380. DOI: 10.1021/acs.joc.9b02465. View

18.

Mitchell E, Peschiulli A, Lefevre N, Meerpoel L, Maes B . Direct α-functionalization of saturated cyclic amines. Chemistry. 2012; 18(33):10092-142. DOI: 10.1002/chem.201201539. View

19.

Singh K, Staig S, Weaver J . Facile synthesis of Z-alkenes via uphill catalysis. J Am Chem Soc. 2014; 136(14):5275-8. DOI: 10.1021/ja5019749. View

20.

Yu C, Shoaib M, Iqbal N, Kim J, Ha H, Cho E . Selective Ring-Opening of N-Alkyl Pyrrolidines with Chloroformates to 4-Chlorobutyl Carbamates. J Org Chem. 2017; 82(13):6615-6620. DOI: 10.1021/acs.joc.7b00681. View