Rhodium(III)-Catalyzed Anti-Markovnikov Hydroamidation of Unactivated Alkenes Using Dioxazolones As Amidating Reagents

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2022 Dec 1

PMID 36453859

Authors

Noah Wagner-Carlberg

Tomislav Rovis

Affiliations

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Abstract

The amide is one of the most prevalent functional groups in all of pharmaceuticals, and for this reason, reactions that introduce the amide moiety are of particular value. Intermolecular hydroamidation of alkenes remains an underexplored method for the synthesis of amide-containing compounds. The majority of hydroamidation procedures exhibit Markovnikov regioselectivity, while current methods for anti-Markovnikov hydroamidation are somewhat limited to activated alkene substrates or radical processes. Herein, we report a general method for the intermolecular anti-Markovnikov hydroamidation of unactivated alkenes under mild conditions, utilizing Rh(III) catalysis in conjunction with dioxazolone amidating reagents and isopropanol as an environmentally friendly hydride source. The reaction tolerates a wide range of functional groups and efficiently converts electron-deficient alkenes, styrenes, and 1,1-disubstituted alkenes, in addition to unactivated alkenes, to their corresponding linear amides. Mechanistic studies reveal a reversible rhodium hydride migratory insertion step, leading to exquisite selectivity for the anti-Markovnikov product.

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References

Bower J, Skucas E, Patman R, Krische M . Catalytic C-C coupling via transfer hydrogenation: reverse prenylation, crotylation, and allylation from the alcohol or aldehyde oxidation level. J Am Chem Soc. 2007; 129(49):15134-5. DOI: 10.1021/ja077389b. View

Lardy S, Schmidt V . Intermolecular Radical Mediated Anti-Markovnikov Alkene Hydroamination Using N-Hydroxyphthalimide. J Am Chem Soc. 2018; 140(39):12318-12322. DOI: 10.1021/jacs.8b06881. View

Jia S, Huang Y, Wang Z, Fan F, Fan B, Sun H . Hydroamination of Unactivated Alkenes with Aliphatic Azides. J Am Chem Soc. 2022; 144(36):16316-16324. DOI: 10.1021/jacs.2c07643. View

Qian H, Widenhoefer R . Platinum-catalyzed intermolecular hydroamination of vinyl arenes with carboxamides. Org Lett. 2005; 7(13):2635-8. DOI: 10.1021/ol050745f. View

Zhu Q, Graff D, Knowles R . Intermolecular Anti-Markovnikov Hydroamination of Unactivated Alkenes with Sulfonamides Enabled by Proton-Coupled Electron Transfer. J Am Chem Soc. 2017; 140(2):741-747. PMC: 6247111. DOI: 10.1021/jacs.7b11144. View

Colebrooke S, Duckett S, Lohman J, Eisenberg R . Hydrogenation studies involving halobis(phosphine)-rhodium(I) dimers: use of parahydrogen induced polarisation to detect species present at low concentration. Chemistry. 2004; 10(10):2459-74. DOI: 10.1002/chem.200305466. View

Lee S, Lei H, Rovis T . A Rh(III)-Catalyzed Formal [4+1] Approach to Pyrrolidines from Unactivated Terminal Alkenes and Nitrene Sources. J Am Chem Soc. 2019; 141(32):12536-12540. PMC: 7428074. DOI: 10.1021/jacs.9b07012. View

Hirano K, Miura M . Hydroamination, Aminoboration, and Carboamination with Electrophilic Amination Reagents: Umpolung-Enabled Regio- and Stereoselective Synthesis of -Containing Molecules from Alkenes and Alkynes. J Am Chem Soc. 2022; 144(2):648-661. DOI: 10.1021/jacs.1c12663. View

Liang T, Woo S, Krische M . C-Propargylation Overrides O-Propargylation in Reactions of Propargyl Chloride with Primary Alcohols: Rhodium-Catalyzed Transfer Hydrogenation. Angew Chem Int Ed Engl. 2016; 55(32):9207-11. PMC: 4965293. DOI: 10.1002/anie.201603575. View

10.

Ma S, Hill C, Olen C, Hartwig J . Ruthenium-Catalyzed Hydroamination of Unactivated Terminal Alkenes with Stoichiometric Amounts of Alkene and an Ammonia Surrogate by Sequential Oxidation and Reduction. J Am Chem Soc. 2020; 143(1):359-368. PMC: 8594411. DOI: 10.1021/jacs.0c11043. View

11.

Maity S, Potter T, Ellman J . α-Branched amines by catalytic 1,1-addition of C-H bonds and aminating agents to terminal alkenes. Nat Catal. 2020; 2(9):756-762. PMC: 7462361. DOI: 10.1038/s41929-019-0330-7. View

12.

Sevov C, Zhou J, Hartwig J . Iridium-catalyzed intermolecular hydroamination of unactivated aliphatic alkenes with amides and sulfonamides. J Am Chem Soc. 2012; 134(29):11960-3. DOI: 10.1021/ja3052848. View

13.

Zhang Z, Lee S, Widenhoefer R . Intermolecular hydroamination of ethylene and 1-alkenes with cyclic ureas catalyzed by achiral and chiral gold(I) complexes. J Am Chem Soc. 2009; 131(15):5372-3. PMC: 2891684. DOI: 10.1021/ja9001162. View

14.

Kim I, Ngai M, Krische M . Enantioselective iridium-catalyzed carbonyl allylation from the alcohol or aldehyde oxidation level via transfer hydrogenative coupling of allyl acetate: departure from chirally modified allyl metal reagents in carbonyl addition. J Am Chem Soc. 2008; 130(44):14891-9. PMC: 2890235. DOI: 10.1021/ja805722e. View

15.

Tomberg A, Bostrom J . Can easy chemistry produce complex, diverse, and novel molecules?. Drug Discov Today. 2020; 25(12):2174-2181. DOI: 10.1016/j.drudis.2020.09.027. View

16.

Xi Y, Ma S, Hartwig J . Catalytic asymmetric addition of an amine N-H bond across internal alkenes. Nature. 2020; 588(7837):254-260. PMC: 8638802. DOI: 10.1038/s41586-020-2919-z. View

17.

Chinn A, Sedillo K, Doyle A . Phosphine/Photoredox Catalyzed Anti-Markovnikov Hydroamination of Olefins with Primary Sulfonamides via α-Scission from Phosphoranyl Radicals. J Am Chem Soc. 2021; 143(43):18331-18338. DOI: 10.1021/jacs.1c09484. View

18.

Vitaku E, Smith D, Njardarson J . Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among U.S. FDA approved pharmaceuticals. J Med Chem. 2014; 57(24):10257-74. DOI: 10.1021/jm501100b. View

19.

Musacchio A, Nguyen L, Beard G, Knowles R . Catalytic olefin hydroamination with aminium radical cations: a photoredox method for direct C-N bond formation. J Am Chem Soc. 2014; 136(35):12217-20. DOI: 10.1021/ja5056774. View

20.

Samec J, Backvall J, Andersson P, Brandt P . Mechanistic aspects of transition metal-catalyzed hydrogen transfer reactions. Chem Soc Rev. 2006; 35(3):237-48. DOI: 10.1039/b515269k. View