Enantioselective Intramolecular C-H Amination of Aliphatic Azides by Dual Ruthenium and Phosphine Catalysis

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2019 Apr 19

PMID 30996902

Citations 13

Authors

Jie Qin

Zijun Zhou

Tianjiao Cui

Marcel Hemming

Eric Meggers

Affiliations

Soon will be listed here.

Abstract

The catalytic enantioselective intramolecular C(sp)-H amination of aliphatic azides represents an efficient method for constructing chiral saturated cyclic amines which constitute a prominent structural motif in bioactive compounds. We report a dual catalytic system involving a chiral-at-metal bis(pyridyl-NHC) ruthenium complex and tris(4-fluorophenyl)phosphine (both 1 mol%), which facilitates the cyclization of aliphatic azides to chiral α-aryl pyrrolidines with enantioselectivities of up to 99% ee, including a pyrrolidine which can be converted to the anti-tumor alkaloid ()-(+)-crispine. Mechanistically, the phosphine activates the organic azide to form an intermediate iminophosphorane and transfers the nitrene unit to the ruthenium providing an imido ruthenium intermediate which engages in the highly stereocontrolled C-H amination. This dual catalysis combines ruthenium catalysis with the Staudinger reaction and provides a novel strategy for catalyzing enantioselective C-H aminations of unactivated aliphatic azides.

Citing Articles

Pyrrolidine synthesis via ring contraction of pyridines.

Ueno R, Hirano S, Takaya J Nat Commun. 2025; 16(1):2426.

PMID: 40082412 PMC: 11906765. DOI: 10.1038/s41467-025-57527-w.

Chiral-at-metal catalysts: history, terminology, design, synthesis, and applications.

Zhang L, Meggers E Chem Soc Rev. 2025; 54(4):1986-2005.

PMID: 39836047 PMC: 11749197. DOI: 10.1039/d4cs01043d.

Biocatalytic Construction of Chiral Pyrrolidines and Indolines via Intramolecular C(sp)-H Amination.

Qin Z, Gao S, Zou Y, Liu Z, Wang J, Houk K ACS Cent Sci. 2024; 9(12):2333-2338.

PMID: 38161360 PMC: 10755850. DOI: 10.1021/acscentsci.3c00516.

Examining the effects of additives and precursors on the reactivity of rhodium alkyl nitrenes generated from substituted hydroxylamines.

Noda H, Asada Y, Shibasaki M Front Chem. 2023; 11:1271896.

PMID: 38025067 PMC: 10654751. DOI: 10.3389/fchem.2023.1271896.

Nitrene transfer catalysts for enantioselective C-N bond formation.

Ju M, Schomaker J Nat Rev Chem. 2023; 5(8):580-594.

PMID: 37117585 DOI: 10.1038/s41570-021-00291-4.

References

OHagan D . Pyrrole, pyrrolidine, pyridine, piperidine and tropane alkaloids. Nat Prod Rep. 2000; 17(5):435-46. DOI: 10.1039/a707613d. View

Ragaini F, Penoni A, Gallo E, Tollari S, Li Gotti C, Lapadula M . Amination of benzylic C-H bonds by arylazides catalyzed by CoII-porphyrin complexes: a synthetic and mechanistic study. Chemistry. 2002; 9(1):249-59. DOI: 10.1002/chem.200390018. View

Leung S, Tsui W, Huang J, Che C, Liang J, Zhu N . Imido transfer from bis(imido)ruthenium(VI) porphyrins to hydrocarbons: effect of imido substituents, C-H bond dissociation energies, and Ru(VI/V) reduction potentials. J Am Chem Soc. 2005; 127(47):16629-40. DOI: 10.1021/ja0542789. View

Campos K, Klapars A, Waldman J, Dormer P, Chen C . Enantioselective, palladium-catalyzed alpha-arylation of N-Boc-pyrrolidine. J Am Chem Soc. 2006; 128(11):3538-9. DOI: 10.1021/ja0605265. View

Ruppel J, Kamble R, Zhang X . Cobalt-catalyzed intramolecular C-H amination with arylsulfonyl azides. Org Lett. 2007; 9(23):4889-92. DOI: 10.1021/ol702265h. View

Albertin G, Antoniutti S, Baldan D, Castro J, Garcia-Fontan S . Preparation of benzyl azide complexes of iridium(III). Inorg Chem. 2007; 47(2):742-8. DOI: 10.1021/ic701907y. View

Badiei Y, Dinescu A, Dai X, Palomino R, Heinemann F, Cundari T . Copper-nitrene complexes in catalytic C-H amination. Angew Chem Int Ed Engl. 2008; 47(51):9961-4. DOI: 10.1002/anie.200804304. View

King E, Betley T . C-H bond amination from a ferrous dipyrromethene complex. Inorg Chem. 2009; 48(6):2361-3. DOI: 10.1021/ic900219b. View

Sun K, Sachwani R, Richert K, Driver T . Intramolecular Ir(I)-catalyzed benzylic C-H bond amination of ortho-substituted aryl azides. Org Lett. 2009; 11(16):3598-601. PMC: 2743533. DOI: 10.1021/ol901317j. View

10.

Fantauzzi S, Gallo E, Caselli A, Ragaini F, Casati N, Macchi P . The key intermediate in the amination of saturated C-H bonds: synthesis, X-ray characterization and catalytic activity of Ru(TPP)(NAr)(2) (Ar = 3,5-(CF(3))(2)C(6)H(3)). Chem Commun (Camb). 2009; (26):3952-4. DOI: 10.1039/b903238j. View

11.

Lloyd J, Finlay H, Vacarro W, Hyunh T, Kover A, Bhandaru R . Pyrrolidine amides of pyrazolodihydropyrimidines as potent and selective KV1.5 blockers. Bioorg Med Chem Lett. 2010; 20(4):1436-9. DOI: 10.1016/j.bmcl.2009.12.085. View

12.

Lu H, Tao J, Jones J, Wojtas L, Zhang X . Cobalt(II)-catalyzed intramolecular C-H amination with phosphoryl azides: formation of 6- and 7-membered cyclophosphoramidates. Org Lett. 2010; 12(6):1248-51. DOI: 10.1021/ol100110z. View

13.

Collet F, Dodd R, Dauban P . Catalytic C-H amination: recent progress and future directions. Chem Commun (Camb). 2010; (34):5061-74. DOI: 10.1039/b905820f. View

14.

Driver T . Recent advances in transition metal-catalyzed N-atom transfer reactions of azides. Org Biomol Chem. 2010; 8(17):3831-46. PMC: 3095841. DOI: 10.1039/c005219c. View

15.

Collet F, Lescot C, Dauban P . Catalytic C-H amination: the stereoselectivity issue. Chem Soc Rev. 2011; 40(4):1926-36. DOI: 10.1039/c0cs00095g. View

16.

Che C, Lo V, Zhou C, Huang J . Selective functionalisation of saturated C-H bonds with metalloporphyrin catalysts. Chem Soc Rev. 2011; 40(4):1950-75. DOI: 10.1039/c0cs00142b. View

17.

Ichinose M, Suematsu H, Yasutomi Y, Nishioka Y, Uchida T, Katsuki T . Enantioselective intramolecular benzylic C-H bond amination: efficient synthesis of optically active benzosultams. Angew Chem Int Ed Engl. 2011; 50(42):9884-7. DOI: 10.1002/anie.201101801. View

18.

Mitch C, Quimby S, Diaz N, Pedregal C, de la Torre M, Jimenez A . Discovery of aminobenzyloxyarylamides as κ opioid receptor selective antagonists: application to preclinical development of a κ opioid receptor antagonist receptor occupancy tracer. J Med Chem. 2011; 54(23):8000-12. DOI: 10.1021/jm200789r. View

19.

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

20.

Nguyen Q, Sun K, Driver T . Rh2(II)-catalyzed intramolecular aliphatic C-H bond amination reactions using aryl azides as the N-atom source. J Am Chem Soc. 2012; 134(17):7262-5. PMC: 3397916. DOI: 10.1021/ja301519q. View