Highly Diastereo‐ and Enantioselective Synthesis of Tetrahydro‐5H‐Indolo[2,3‐b]quinolines through Copper‐Catalyzed Propargylic Dearomatization of Indoles

Abstract

The first copper-catalyzed intermolecular asymmetric propargylic dearomatization/annulation cascade sequence of indoles via a copper-allenylidene amphiphilic intermediate has been achieved. This protocol provides a direct asymmetric synthetic method for the preparation of tetrahydro-5H-indolo[2,3-b]quinolines, the core structure of indole alkaloids communesins A-H and perophoramidine. This method features excellent yields, high diastereoselectivity (up to >19:1 d.r.) and enantioselectivity (up to 94 % ee), mild conditions and wide substrate scope.

Base‐Mediated Decarboxylative [3+2] Annulation of Ethynyl Benzoxazinanones and Benzimidamides: Synthesis of Imidazole Derivatives

“…When transition metal catalyst such as copper catalyst was used, the propargylic compounds generate metal‐allenylidene intermediates through decarboxylation, which then work as an electrophile to furnish diverse annulation reactions [1,2] . Generally, in the presence of a copper catalyst, ethynyl benzoxazinanones produced the copper‐allenylidene intermediates, which act as a four, three or two‐membered synthon to accomplish intermolecular [4+n], [3+n] and [2+n] annulations (Scheme 1a) [3–13] . The versatility of copper‐allenylidene as four‐membered synthon had been demonstrated by [4+1] annulation of ethynyl benzoxazinanones with sulfur ylides, [3] several asymmetric [4+2] annulation reactions of ethynyl benzoxazinanones with different bisnucleophiles, [4–10] and asymmetric [4+3] cycloaddition of ethynyl benzoxazinanones with C,N‐cyclic azomethine imines [11] .…”

Formal [3+2] Annulation of Copper‐Allenylidenes with 3‐Oxo‐3‐Arylpropanenitriles: Synthesis of Tetrasubstituted Furans

“…Xiao and Lu reported [4+1] annulation of the above intermediate with sulfur ylides [8] . Several highly enantioselective [4+2] annulations were disclosed by Gong, [9] Wu, [10] You, [11] Sun, [12] Wang [13] and Mukherjee [14] . Gong [15] and Jiang [16] accomplished catalytic asymmetric [4+3] cycloaddition of copper allenylidenes with isatin‐derived enals or C,N‐cyclic azomethine imines.…”

Recent Developments in Transition Metal‐Catalyzed Dearomative Cyclizations of Indoles as Dipolarophiles for the Construction of Indolines

“…Catalytic cyclization reactions featuring Cu‐allenylidene amphiphilic intermediates generated from ethynylbenzoxazinanone via decarboxylation have been studied by several groups in the past decade . In 2017, You and a co‐worker disclosed Cu‐catalyzed asymmetric dearomative [4+2] cyclization reactions of substituted indoles 22 with Cu‐allenylidene 1,4‐dipoles 172 derived in situ from ethynylbenzoxazinanones 168 (Scheme ) . This flexible strategy allowed the synthesis of a broad range of tetrahydroquinolinoindolines 169 , which represent the core skeleton of the indole alkaloids communesins A–H and perophoramidine, in good yields and with high diastereoselectivities (up to dr >19:1) and enantioselectivities (up to 94% ee ).…”