Special Edition Thieme Chemistry Journals Awardees 2022
Rhodium(III) Iodide Catalyzed Carboamination of Alkynes through C–N Bond Activation
XinXin Li
a
Molecular Synthesis Center and Key Laboratory of Marine Drugs, Ministry of Education; School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, P. R. of China
,
Qingxing Yang
a
Molecular Synthesis Center and Key Laboratory of Marine Drugs, Ministry of Education; School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, P. R. of China
,
Yuna Zhang
a
Molecular Synthesis Center and Key Laboratory of Marine Drugs, Ministry of Education; School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, P. R. of China
a
Molecular Synthesis Center and Key Laboratory of Marine Drugs, Ministry of Education; School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao 266003, P. R. of China
b
Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology, 1 Wenhai Road, Qingdao 266237, P. R. of China
› Author AffiliationsNational Science Foundation of China (Nos. 82122063, 81991522, and 81973232); Shandong Science Fund for Distinguished Young Scholars (ZR2020JQ32); Fundamental Research Funds for the Central Universities (202041003); and Marine S&T Fund of Shandong Province for Pilot NLMST (2022QNLM030003-2).
Here, we report a RhI3-catalyzed intramolecular carboamination reaction to access polysubstituted indoles. The protocol features a broad substrate scope (>20 examples), good functional-group compatibility, and a low catalyst loading (5 mol% Rh). Good to excellent yields (up to 98%) were obtained. An unprecedented C–N bond-cleavage mode via a six-membered transition state σ-bond metathesis mechanism was proposed based on control experiments. A series of C3-allylated indole derivatives were accessed, proving that the system provides an alternative catalytic route to polysubstituted indoles.
8 CCDC 2215689 contains the supplementary crystallographic data for compound 7. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures
9
Zhang J,
Wang X,
Xu T.
Nat. Commun. 2021; 12: 3022
141-Methyl-3-(2-methylprop-2-en-1-yl)-2-phenyl-1H-indole (2a); Typical Procedure
In a nitrogen-filled glove box, an oven-dried 4 mL vial was charged with amine 1a (23.7 mg, 0.091 mmol) and RhI3 (2.3 mg, 0.005 mmol). Toluene (1 mL) was added, and the mixture was stirred at rt for 5 minutes until the solids fully dissolved. The vial was then sealed with a PTFE-lined cap and the mixture was stirred for 12 h on a pie-block preheated to 120 °C. The mixture was then directly filtered through Celite and silica gel, which were washed with EtOAc (20 mL). The solvent was removed under reduced pressure, and the crude residue was purified by flash column chromatography (silica gel) to give a yellow oil; yield: 22.9 mg (98%).
IR (FTIR): 3056, 2907, 1647, 1466, 1361, 1014, 890 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.64 (d, J = 7.8 Hz, 1 H), 7.53–7.47 (m, 2 H), 7.47–7.40 (m, 3 H), 7.37 (d, J = 8.2 Hz, 1 H), 7.30–7.24 (m, 1 H), 7.15 (ddd, J = 7.9, 6.9, 1.0 Hz, 1 H), 4.78 (s, 1 H), 4.70 (s, 1 H), 3.64 (s, 3 H), 3.40 (s, 2 H), 1.73 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 145.5, 138.7, 137.4, 132.1, 130.6, 128.4, 128.2, 128.1, 121.7, 119.7, 119.3, 110.8, 110.8, 109.4, 33.4, 31.1, 22.9. HRMS (ESI): m/z [M + Na]+ calcd for C19H19NNa: 284.1410; found: 284.1409.
