Synthesis of Pyrrolo[2,1-a]isoquinolines through Cu-Catalyzed Condensation/Addition/Oxidation/Cyclization Cascade

Abstract

We have developed a copper-catalyzed synthesis of pyrrolo[2,1-a]isoquinolines with terminal alkynes, aldehydes, and tetrahydroisoquinolines. A variety of pyrrolo[2,1-a]isoquinolines have been prepared in 17−69% yield via a condensation/Mannichtype addition/oxidation/cyclization cascade sequence. Modifications through simple chemical transformations provided highly functionalized molecules containing a privileged framework.

NH4OAc/DMSO-Promoted Benzylation of Pyrrolo[2,1-a]isoquinolines

“…FeCl 3 was purchased from Shanghai Titan Scientific Co., Ltd. (≥98%). Compounds 1 and 4 were prepared following our reported procedures . All compounds 1 and 4 were known compounds.…”

Photocatalytic Oxidative [3+2] Cycloaddition for Pyrrolo[2,1‐a]isoquinoline Synthesis Using a Porphyrin‐Based Covalent Organic Framework

“…Therefore, great efforts have been devoted to the development of methodologies for the construction of pyrrolo[2,1‐ a ]isoquinolines, including electrocyclization pathway, double‐barreled Heck cyclization, and so on [6–15] . Among them, the dipolar [3+2] cycloadditions between azomethine ylides and dipolarophiles have attracted special attention, because it allows the construction of pyrrolo[2,1‐ a ]isoquinolines in a straightforward and convenient way [16–26] . In this strategy, a variety of metal complexes based on Cu (II), Co(II), Rh(II), or molecular KI, I 2 , N ‐heterocyclic carbene were employed as the catalysts in conjunction with suitable oxidants.…”

“…[6][7][8][9][10][11][12][13][14][15] Among them, the dipolar [3 + 2] cycloadditions between azomethine ylides and dipolarophiles have attracted special attention, because it allows the construction of pyrrolo [2,1-a]isoquinolines in a straightforward and convenient way. [16][17][18][19][20][21][22][23][24][25][26] In this strategy, a variety of metal complexes based on Cu (II), Co(II), Rh(II), or molecular KI, I 2 , N-heterocyclic carbene were employed as the catalysts in conjunction with suitable oxidants. Recently, the use of visible light mediated photoredox catalysis [27][28][29][30][31] as an eco-friendly and powerful synthetic technique for the dipolar [3 + 2] cycloaddition reaction has also been reported, with [Ru(bpy) 3 ]Cl 2 , Bodipy species, Rose Bengal or Methylene Blue as the photocatalyst.…”

Mechanosynthesis of Pyrrole-2-carboxylic Acids via Copper-Catalyzed Spiroannulation/Ring-Opening Aromatization of 4-Arylidene Isoxazol-5-ones with Enamino Esters

“…13 Cui's group reported a CuCl 2 -catalyzed multicomponent synthesis of pyrrole derivatives from tetrahydroisoquinolines, aldehydes, and terminal alkynes. 14 Ye et al achieved a CuBr-catalyzed [4 + 1] annulation of N-propargyl ynamides with diketones and synthesized a series of dioxole-substituted pyrroles. 15 Recently, a novel CuTc-catalyzed trisannulation of α,β-unsaturated ketoximes with 1,3-dicarbonyls and paraformaldehyde to access 2,3disubstituted pyrroles was developed by Duan's group.…”

“…The Córdova and Bäckvall group disclosed a Cu-AmP-MCC-catalyzed and solvent-controlled pyrrole synthesis via intramolecular cyclization of allenynamides . Cui’s group reported a CuCl 2 -catalyzed multicomponent synthesis of pyrrole derivatives from tetrahydroisoquinolines, aldehydes, and terminal alkynes . Ye et al.…”