Catalytic Dehydrogenative Synthesis of α,β-unsaturated Secondary Amides Without External Oxidants

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2024 Sep 9

PMID 39246373

Authors

Shaokang An

Guoyin Lai

Wenbo H Liu

Affiliations

Soon will be listed here.

Abstract

Direct dehydrogenative synthesis of α,β-unsaturated secondary amides still represents an elusive transformation. Herein we describe a palladium-catalyzed redox-neutral desaturation to prepare α,β-conjugated secondary amides. Without external oxidants, this approach relies on the N-O bond cleavage as the driving force to achieve formal dehydrogenation. Complementary to known protocols, this transformation is enabled by the unique reactivity of hydroxamate, thereby representing a novel strategy to accomplish carbonyl desaturation. Desired conjugated secondary amides can be efficiently synthesized in the presence of more reactive esters and even ketones, thus providing a solution to the long-standing issue of α,β-unsaturated secondary amides C-C desaturation.

Citing Articles

Redox-Neutral Umpolung Synthesis of α-Functionalized Amides.

Wang R, An S, Xin Y, Jiang Y, Liu W JACS Au. 2024; 4(11):4435-4444.

PMID: 39610725 PMC: 11600186. DOI: 10.1021/jacsau.4c00767.

References

Bissember A, Levina A, Fu G . A mild, palladium-catalyzed method for the dehydrohalogenation of alkyl bromides: synthetic and mechanistic studies. J Am Chem Soc. 2012; 134(34):14232-7. PMC: 3432975. DOI: 10.1021/ja306323x. View

Girard S, Knauber T, Li C . The cross-dehydrogenative coupling of C(sp3)-H bonds: a versatile strategy for C-C bond formations. Angew Chem Int Ed Engl. 2013; 53(1):74-100. DOI: 10.1002/anie.201304268. View

Fukui Y, Liu P, Liu Q, He Z, Wu N, Tian P . Tunable arylative cyclization of 1,6-enynes triggered by rhodium(III)-catalyzed C-H activation. J Am Chem Soc. 2014; 136(44):15607-14. DOI: 10.1021/ja5072702. View

Yu W, Ren Z, Ma K, Yang H, Yang J, Zheng H . Cobalt-catalyzed chemoselective dehydrogenation through radical translocation under visible light. Chem Sci. 2022; 13(26):7947-7954. PMC: 9258329. DOI: 10.1039/d2sc02291e. View

Huang D, Szewczyk S, Zhang P, Newhouse T . Allyl-Nickel Catalysis Enables Carbonyl Dehydrogenation and Oxidative Cycloalkenylation of Ketones. J Am Chem Soc. 2019; 141(14):5669-5674. PMC: 7495923. DOI: 10.1021/jacs.9b02552. View

Chen M, Dong G . Copper-Catalyzed Desaturation of Lactones, Lactams, and Ketones under pH-Neutral Conditions. J Am Chem Soc. 2019; 141(37):14889-14897. DOI: 10.1021/jacs.9b07932. View

Li C . Cross-dehydrogenative coupling (CDC): exploring C-C bond formations beyond functional group transformations. Acc Chem Res. 2009; 42(2):335-44. DOI: 10.1021/ar800164n. View

Guimond N, Gorelsky S, Fagnou K . Rhodium(III)-catalyzed heterocycle synthesis using an internal oxidant: improved reactivity and mechanistic studies. J Am Chem Soc. 2011; 133(16):6449-57. DOI: 10.1021/ja201143v. View

Zard S . Recent progress in the generation and use of nitrogen-centred radicals. Chem Soc Rev. 2008; 37(8):1603-18. DOI: 10.1039/b613443m. View

10.

Wang Z, He Z, Zhang L, Huang Y . Iridium-Catalyzed Aerobic α,β-Dehydrogenation of γ,δ-Unsaturated Amides and Acids: Activation of Both α- and β-C-H bonds through an Allyl-Iridium Intermediate. J Am Chem Soc. 2017; 140(2):735-740. DOI: 10.1021/jacs.7b11351. View

11.

Chen Y, Romaire J, Newhouse T . Palladium-Catalyzed α,β-Dehydrogenation of Esters and Nitriles. J Am Chem Soc. 2015; 137(18):5875-8. DOI: 10.1021/jacs.5b02243. View

12.

Chen M, Rago A, Dong G . Platinum-Catalyzed Desaturation of Lactams, Ketones, and Lactones. Angew Chem Int Ed Engl. 2018; 57(49):16205-16209. DOI: 10.1002/anie.201811197. View

13.

Wang M, Sui G, Cui X, Wang H, Qu J, Kang Y . Radical α,β-Dehydrogenation of Saturated Amides via α-Oxidation with TEMPO under Transition Metal-Free Conditions. J Org Chem. 2019; 84(12):8267-8274. DOI: 10.1021/acs.joc.9b00872. View

14.

Wang H, Grohmann C, Nimphius C, Glorius F . Mild Rh(III)-catalyzed C-H activation and annulation with alkyne MIDA boronates: short, efficient synthesis of heterocyclic boronic acid derivatives. J Am Chem Soc. 2012; 134(48):19592-5. DOI: 10.1021/ja310153v. View

15.

Yang S, Fan H, Xie L, Dong G, Chen M . Photoinduced Desaturation of Amides by Palladium Catalysis. Org Lett. 2022; 24(35):6460-6465. DOI: 10.1021/acs.orglett.2c02594. View

16.

Bauer A, Maulide N . Chemoselective formal β-functionalization of substituted aliphatic amides enabled by a facile stereoselective oxidation event. Chem Sci. 2020; 10(42):9836-9840. PMC: 6977552. DOI: 10.1039/c9sc03715b. View

17.

Tan Y, Hartwig J . Palladium-catalyzed amination of aromatic C-H bonds with oxime esters. J Am Chem Soc. 2010; 132(11):3676-7. DOI: 10.1021/ja100676r. View

18.

Teskey C, Adler P, Goncalves C, Maulide N . Chemoselective α,β-Dehydrogenation of Saturated Amides. Angew Chem Int Ed Engl. 2018; 58(2):447-451. PMC: 6348382. DOI: 10.1002/anie.201808794. View

19.

Chen Y, Turlik A, Newhouse T . Amide α,β-Dehydrogenation Using Allyl-Palladium Catalysis and a Hindered Monodentate Anilide. J Am Chem Soc. 2016; 138(4):1166-9. DOI: 10.1021/jacs.5b12924. View

20.

Yeung C, Dong V . Catalytic dehydrogenative cross-coupling: forming carbon-carbon bonds by oxidizing two carbon-hydrogen bonds. Chem Rev. 2011; 111(3):1215-92. DOI: 10.1021/cr100280d. View