Pyrrole Functionalization by Copper‐Catalyzed Nitrene Transfer Reactions

Abstract

The catalytic functionalization of pyrroles by incorporation of a nitrene group is reported. The Cα-H bond of 1H-pyrrole is amidated upon the formal insertion of the NTs (Ts = p-toluenesulfonyl) group catalyzed by Tp Br3 Cu (NCMe) (Tp Br3 = hydrotris(3,4,5-tribromo-pyrazolyl)borate). N-substituted pyrroles also verify the same transformation. The mechanism proposal is similar to that previously described for benzene amidation with the same catalyst and PhI=NTs, which takes place through aziridine formation, ring opening and 1,2-hydrogen shift. A cascade reaction involving the coupling of 2,5-dimethylfuran, 1,2,3-trimethyl-pyrrole and a nitrene NTs group is also described, leading to a 1,2dihydropyridine-imine compound. Scheme 1. Most common CÀ N bond formation by metal catalysed nitrene insertion: olefin aziridination and CÀ H amidation. Scheme 2. Left: potential reaction sites toward attack by the metalÀ nitrene species. This work: the reaction with 1H-or Nsubstituted pyrroles takes place onto the C sp2 À H bond in an exclusive manner. Scheme 4. Substituted pyrroles as substrates. Scheme 5. Competition experiments toward relative reactivity.

Recent Advances in Functionalization of Pyrroles and their Translational Potential

“…The proposed mechanism depicted benzene amidation with the catalyst and PhI=NTs, undergoing via aziridine formation, ring opening and 1,2‐hydrogen shift. A cascade reaction including the coupling of 2,5‐dimethylfuran, 1,2,3‐trimethyl‐pyrrole and a nitrene bunch is clarified prompting a 1,2‐dihydropyridine‐imine compound [69] . Further in 2020, Jiang et al .…”

Theoretical Exploration of Energy Transfer and Single Electron Transfer Mechanisms to Understand the Generation of Triplet Nitrene and the C(sp3)–H Amidation with Photocatalysts

“…As a prominent example, nitrene can be applied as a critical reactive intermediate for the synthesis of valuable N-containing molecules, − which is mainly generated by the photolysis of various precursors. ,− However, the direct photolysis of nitrene precursors requires very harsh short-wavelength irradiation, which leads to poor functional group tolerance and competitive photodecomposition processes that diminish the reaction yield. − The strategy of indirect excitation with the help of visible-light photocatalysts, for example, polypyridyl complexes of ruthenium or iridium, was used to overcome this problem. In 2011, Liu and co-workers first reported that a nitrene radical anion can be generated by one-electron reduction of the aryl azide, in which [Ru­(bpy) 3 ] 2+ was employed as the photocatalyst .…”