Ligand Enabled Pd(II)-Catalyzed γ-C(sp)-H Lactamization of Native Amides

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2021 Dec 16

PMID 34914877

Citations 7

Authors

Shuang Liu

Zhe Zhuang

Jennifer X Qiao

Kap-Sun Yeung

Shun Su

Emily C Cherney

Zheming Ruan

William R Ewing

Michael A Poss

Jin-Quan Yu

Affiliations

Soon will be listed here.

Abstract

γ-Lactams form important structural cores of a range of medicinally relevant natural products and clinical drugs, principal examples being the new generation of immunomodulatory imide drugs (IMiDs) and the brivaracetam family. Compared to conventional multistep synthesis, an intramolecular γ-C-H amination of aliphatic amides would allow for the direct construction of valuable γ-lactam motifs from abundant amino acid precursors. Herein we report a novel 2-pyridone ligand enabled Pd(II)-catalyzed γ-C(sp)-H lactamization of amino acid derived native amides, providing the convenient synthesis of γ-lactams, isoindolinones, and 2-imidazolidinones. C6-Substitution of the 2-pyridone ligand is crucial for the lactam formation. This protocol features the use of -acyl amino acids, which serve as both the directing group and cyclization partner, practical and environmentally benign -butyl hydrogen peroxide (TBHP) as the sole bystanding oxidant, and a broad substrate scope. The utility of this protocol was demonstrated through the two-step syntheses of a lenalidomide analog and brivaracetam from readily available carboxylic acids and amino acids.

Citing Articles

Synthesis of Lactams via a Chiral Phosphoric Acid-Catalyzed Aniline Cyclization.

Horchar A, Dean J, Lake A, Carsley J, Lillevig T, Liu S J Org Chem. 2024; 89(17):12725-12738.

PMID: 39120519 PMC: 11382273. DOI: 10.1021/acs.joc.4c01060.

In Silico Analysis: Anti-Inflammatory and α-Glucosidase Inhibitory Activity of New α-Methylene-γ-Lactams.

Hernandez-Guadarrama A, Diaz-Roman M, Linzaga-Elizalde I, Dominguez-Mendoza B, Aguilar-Guadarrama A Molecules. 2024; 29(9).

PMID: 38731463 PMC: 11085531. DOI: 10.3390/molecules29091973.

Palladium (II)-Catalyzed C-H Activation with Bifunctional Ligands: From Curiosity to Industrialization.

Wu K, Lam N, Strassfeld D, Fan Z, Qiao J, Liu T Angew Chem Int Ed Engl. 2024; 63(19):e202400509.

PMID: 38419352 PMC: 11216193. DOI: 10.1002/anie.202400509.

Pd-Catalyzed -C(sp)-H (Hetero)Arylation of Ketones Enabled by Transient Directing Groups.

Li Y, Ouyang Y, Chekshin N, Yu J ACS Catal. 2023; 12(17):10581-10586.

PMID: 37305173 PMC: 10249709. DOI: 10.1021/acscatal.2c03400.

Dual ligand approach increases functional group tolerance in the Pd-catalysed C-H arylation of -heterocyclic pharmaceuticals.

Beckers I, Bugaev A, De Vos D Chem Sci. 2023; 14(5):1176-1183.

PMID: 36756333 PMC: 9891385. DOI: 10.1039/d2sc04911b.

References

Lopez-Girona A, Mendy D, Ito T, Miller K, Gandhi A, Kang J . Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia. 2012; 26(11):2326-35. PMC: 3496085. DOI: 10.1038/leu.2012.119. View

Gong W, Zhang G, Liu T, Giri R, Yu J . Site-selective C(sp3)-H functionalization of di-, tri-, and tetrapeptides at the N-terminus. J Am Chem Soc. 2014; 136(48):16940-6. PMC: 4277765. DOI: 10.1021/ja510233h. View

Wu X, Yang K, Zhao Y, Sun H, Li G, Ge H . Cobalt-catalysed site-selective intra- and intermolecular dehydrogenative amination of unactivated sp(3) carbons. Nat Commun. 2015; 6:6462. PMC: 4366490. DOI: 10.1038/ncomms7462. View

Wang P, Farmer M, Huo X, Jain P, Shen P, Ishoey M . Ligand-Promoted Meta-C-H Arylation of Anilines, Phenols, and Heterocycles. J Am Chem Soc. 2016; 138(29):9269-76. PMC: 5512281. DOI: 10.1021/jacs.6b04966. View

Xia G, Zhuang Z, Liu L, Schreiber S, Melillo B, Yu J . Ligand-Enabled β-Methylene C(sp )-H Arylation of Masked Aliphatic Alcohols. Angew Chem Int Ed Engl. 2020; 59(20):7783-7787. PMC: 7219561. DOI: 10.1002/anie.202000632. View

Ito T, Ando H, Suzuki T, Ogura T, Hotta K, Imamura Y . Identification of a primary target of thalidomide teratogenicity. Science. 2010; 327(5971):1345-50. DOI: 10.1126/science.1177319. View

Piwowarska N, Banala S, Overkleeft H, Sussmuth R . Arg-Thz is a minimal substrate for the N(α),N(α)-arginyl methyltransferase involved in the biosynthesis of plantazolicin. Chem Commun (Camb). 2013; 49(91):10703-5. DOI: 10.1039/c3cc45898a. View

Kim M, Mulcahy J, Espino C, Du Bois J . Expanding the substrate scope for C-H amination reactions: oxidative cyclization of urea and guanidine derivatives. Org Lett. 2006; 8(6):1073-6. DOI: 10.1021/ol052920y. View

Jung H, Chang S, Hong S . Strategic Approach to the Metamorphosis of γ-Lactones to NH γ-Lactams via Reductive Cleavage and C-H Amidation. Org Lett. 2019; 21(17):7099-7103. DOI: 10.1021/acs.orglett.9b02673. View

10.

He G, Zhao Y, Zhang S, Lu C, Chen G . Highly efficient syntheses of azetidines, pyrrolidines, and indolines via palladium catalyzed intramolecular amination of C(sp3)-H and C(sp2)-H bonds at γ and δ positions. J Am Chem Soc. 2011; 134(1):3-6. DOI: 10.1021/ja210660g. View

11.

Zhang M, Wang Q, Peng Y, Chen Z, Wan C, Chen J . Transition metal-catalyzed sp C-H activation and intramolecular C-N coupling to construct nitrogen heterocyclic scaffolds. Chem Commun (Camb). 2019; 55(87):13048-13065. DOI: 10.1039/c9cc06609h. View

12.

Zhuang Z, Herron A, Liu S, Yu J . Rapid Construction of Tetralin, Chromane, and Indane Motifs via Cyclative C-H/C-H Coupling: Four-Step Total Synthesis of (±)-Russujaponol F. J Am Chem Soc. 2021; 143(2):687-692. PMC: 8159174. DOI: 10.1021/jacs.0c12484. View

13.

Abada E, Zavalij P, Vedernikov A . Reductive C(sp)-N Elimination from Isolated Pd(IV) Amido Aryl Complexes Prepared Using HO as Oxidant. J Am Chem Soc. 2017; 139(2):643-646. DOI: 10.1021/jacs.6b12648. View

14.

Wang P, Farmer M, Yu J . Ligand-Promoted meta-C-H Functionalization of Benzylamines. Angew Chem Int Ed Engl. 2017; 56(18):5125-5129. PMC: 5512280. DOI: 10.1002/anie.201701803. View

15.

Mandal N, Datta A . Harnessing the Efficacy of 2-Pyridone Ligands for Pd-Catalyzed (β/γ)-C(sp)-H Activations. J Org Chem. 2020; 85(20):13228-13238. DOI: 10.1021/acs.joc.0c02210. View

16.

Zhu R, Li Z, Park H, Senanayake C, Yu J . Ligand-Enabled γ-C(sp)-H Activation of Ketones. J Am Chem Soc. 2018; 140(10):3564-3568. PMC: 5851877. DOI: 10.1021/jacs.8b01359. View

17.

Xing Q, Chan C, Yeung Y, Yu W . Ruthenium(II)-Catalyzed Enantioselective γ-Lactams Formation by Intramolecular C-H Amidation of 1,4,2-Dioxazol-5-ones. J Am Chem Soc. 2019; 141(9):3849-3853. DOI: 10.1021/jacs.9b00535. View

18.

Hill D, Yu J, Blackmond D . Insights into the Role of Transient Chiral Mediators and Pyridone Ligands in Asymmetric Pd-Catalyzed C-H Functionalization. J Org Chem. 2020; 85(21):13674-13679. DOI: 10.1021/acs.joc.0c01798. View

19.

Giri R, Liang J, Lei J, Li J, Wang D, Chen X . Pd-catalyzed stereoselective oxidation of methyl groups by inexpensive oxidants under mild conditions: a dual role for carboxylic anhydrides in catalytic C--H bond oxidation. Angew Chem Int Ed Engl. 2005; 44(45):7420-4. DOI: 10.1002/anie.200502767. View

20.

Kweon J, Chang S . Highly Robust Iron Catalyst System for Intramolecular C(sp )-H Amidation Leading to γ-Lactams. Angew Chem Int Ed Engl. 2020; 60(6):2909-2914. DOI: 10.1002/anie.202013499. View