Light‐Driven Intramolecular C−N Cross‐Coupling via a Long‐Lived Photoactive Photoisomer Complex

Abstract

Reported herein is a visible‐light‐driven intramolecular C−N cross‐coupling reaction under mild reaction conditions (metal‐ and photocatalyst‐free, at room temperature) via a long‐lived photoactive photoisomer complex. This strategy was used to rapidly prepare the N‐substituted polycyclic quinazolinone derivatives with a broad substrate scope (>50 examples) and further exploited to synthesize the natural products tryptanthrin, rutaecarpine, and their analogues. The success of gram‐scale synthesis and solar‐driven transformation, as well as promising tumor‐suppressing biological activity, proves the potential of this strategy for practical applications. Mechanistic investigations, including control experiments, DFT calculations, UV‐vis spectroscopy, EPR, and X‐ray single‐crystal structure of the key intermediate, provides insight into the mechanism.

Visible-Light-Mediated Synthesis of Rutaecarpine Alkaloids through C–N Cross-Coupling Reaction

“…Initially, 2-aminobenzamide (2a) was chosen as the model substrate to investigate C-N cross coupling reactions under the irradiation with 220 Watt • m -2 , 395 nm light, (Table 1). It was reported the phosphate catalysts worked well in this visiblelight-driven C-N cross-coupling reaction based on 2-aminobenzamide derivatives by Zheng's group 23 . We first tried methyl phosphate as a catalyst.…”

“…22 Recently a visible-light-driven intramolecular C-N cross-coupling reaction was used to prepare the N-substituted polycyclic quinazolinone derivatives by Zheng's group. 23 In the reaction a long-lived photoactive photoisomer complex was formed and metal catalysts and photo-catalysts were free. For our research interest resides in the investigation on the synthesis and bioactivity of quinazolinone alkaloids, 24 this article reported using the lightdriven intramolecular C-N cross-coupling reaction to synthesis rutaecarpine and its derivatives, as depicted in Scheme 1e.…”

“…The longlived photoenolization complex II is obtained by the coordination of (R)-BPA through the hydrogen bonding interaction. 23 Then the radical pair III is generated by a SET process induced by irradiation of visible light. Then the superoxide radical anion O2 •abstracts a H + from the amino radical cation to generate the amino radical IV, 25a followed by an intramolecular 1, 6-HAT process, 25b thereby affording the carbon-centered radical V. Next, the radical recombination of V and HO2 • gives the crucial intermediate VI, an active hydroperoxide species.…”

“…Then the superoxide radical anion O2 •abstracts a H + from the amino radical cation to generate the amino radical IV, 25a followed by an intramolecular 1, 6-HAT process, 25b thereby affording the carbon-centered radical V. Next, the radical recombination of V and HO2 • gives the crucial intermediate VI, an active hydroperoxide species. 23 The following reactions could be accomplished in two paths. In the path A, the ketone intermediate VII is produced via the e li mi n a t i o n o f o n e wa te r m o le c ul e f r o m VI.…”

Recent Advances in Photocatalytic C–N Bond Coupling Reactions

“…Zheng and co-workers have reported a long-lived photoactive photoisomer complex for intramolecular C-N coupling reactions (Scheme 76). 80 More than fifty N-substitut-ed polycyclic quinazolinones were synthesized using a catalytic amount of a phosphoric acid [(R)-binol-phosphoric acid] [(R)-BPA] and 2.0 equivalents of pinacolborane as the reducing agent. Initiated by the coordination of (R)-BPA to the starting material through hydrogen bonding, a SET process can be induced to produce an N-centered radical.…”