Rapid and practical access to diverse quindolines by catalyst-free and regioselectivity-reversed Povarov reaction

Zhang, Yingqi; Zhang, Yiping; Zheng, Yan-Xin; Li, Zhaoyang; Ye, Long‐Wu

doi:10.1016/j.xcrp.2021.100448

Cited by 34 publications

(5 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the contrary, the occurrence of transfer hydrogenation between LZU-600-imine and H 2 PTCQ was prevented in the solid phase. Alternatively, aerobic oxidation 92 of H 2 PTCQ (Path B) dominated the formation of LZU-600, the high selectivity of which was therefore governed by intramolecular dehydroaromatization. This discrepancy emphasized that, in addition to the difference in reactivity, the reaction pathway may further be altered: only the transition states restricted in confined spaces are allowed in the COF synthesis.…”

Section: ■ Discussionmentioning

confidence: 99%

Fused-Ring-Linked Covalent Organic Frameworks

Feng

Zhang

et al. 2022

J. Am. Chem. Soc.

View full text Add to dashboard Cite

The development of linkage chemistry in the research area of covalent organic frameworks (COFs) is fundamentally important for creating robust structures with high crystallinity and diversified functionality. We reach herein a new level of complexity and controllability in linkage chemistry by achieving the first synthesis of fused-ring-linked COFs. A series of bicyclic pyrano [4,3-b]pyridine COFs have been constructed via a cascade protocol involving Schiffbase condensation, intramolecular [4 + 2] cycloaddition, and dehydroaromatization. With a broad scope of Brønsted or Lewis acids as the catalyst, the designed monomers, that is, O-propargylic salicylaldehydes and multitopic anilines, were converted into the fused-ring-linked frameworks in a one-pot fashion. The obtained COFs exhibited excellence in terms of purity, stability, and crystallinity, as comprehensively characterized by solid-state nuclear magnetic resonance (NMR) spectroscopy, powder X-ray diffraction, high-resolution transmission electron microscopy, and so on. Specifically, the highly selective formation (>94%) of pyrano [4,3-b]pyridine linkage was verified by quantitative NMR measurements combined with 13 C-labeling synthesis. Moreover, the fused-ring linkage possesses fully locked conformation, which benefits to the high crystallinity observed for these COFs. Advancing the linkage chemistry from the formation of solo bonds or single rings to that of fused rings, this study has opened up new possibilities for the concise construction of sophisticated COF structures with high controllability.

show abstract

Section: ■ Discussionmentioning

confidence: 99%

Fused-Ring-Linked Covalent Organic Frameworks

Feng

Zhang

et al. 2022

J. Am. Chem. Soc.

View full text Add to dashboard Cite

show abstract

“… 1 Due to its importance, development of efficient methods to construct the THQ skeleton has been extensively explored in organic synthesis. Various approaches have been established, including intramolecular cyclization, 2 Povarov reactions, 3 hydrogenation of quinolines 4 and others. 5 Among all the strategies, the oxidative Povarov reaction, a dehydrogenative [4 + 2] annulation reaction between N -alkylanilines and alkenes, represents a promising protocol for the construction of THQs from simple starting materials ( Scheme 1a ).…”

Section: Introductionmentioning

confidence: 99%

Borane-catalyzed cascade Friedel–Crafts alkylation/[1,5]-hydride transfer/Mannich cyclization to afford tetrahydroquinolines

et al. 2022

View full text Add to dashboard Cite

show abstract

“…To our surprise, in all the investigated azido-quinone substrates, it is fascinating to note that we did not observe Povarov type [4 + 2] annulation product 4A1 with the elimination of HN 3 , and the other feasible regioisomeric p -quinone fused 4-substituted-1,5-benzodiazepine 4A2 either via iminodiazonium ionic intermediate followed by intramolecular cyclization with the extrusion of dinitrogen or through intermolecular C–H amination of azidoquinone with aniline (refer to Supporting Information Discussions S312 for details). Hence, we conducted a comparative experiment to understand the reaction course of azido-quinone versus α-phenyl-vinyl azide.…”

Section: Resultsmentioning

confidence: 89%

“…Given the biological importance of the privileged quinoline-5,8-dione scaffold 20 in pharmaceuticals and natural products such as streptonigrin and lavendamycin, we extended this protocol to synthesize quinoline-5,8-dione fused 5-substituted-1,4-benzodiazepines (Figure 6). The reaction of 7-azidoquinoline-5,8-dione 25 with 3,5-dimethylaniline 2a and p-tolualdehyde 3a using standard conditions at 100 °C afforded a complex mixture of tarry products.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Direct Access to Quinone-Fused 5-Substituted-1,4-Benzodiazepine Scaffolds from Azidoquinones with/without [1,2]-Azide-Nitrogen Migration: Mechanistic Insights

Krishnan,

Kamaraj

2023

J. Org. Chem.

View full text Add to dashboard Cite

Seven-membered nitrogen heterocycles have a strong influence in drug discovery due to their inherent 3D character, which allows the ability to explore a vast conformational space with a biological target. Notably, the privileged 1,4-benzodiazepine scaffold is dominant in treating the central nervous system due to its binding affinity with the GABAA receptor. Herein, we report a protocol for the transformation of azidoquinones to p-quinone fused 5-substituted-1,4-benzodiazepines (p-QBZDs) from InCl3-catalyzed intermolecular tandem cycloannulation of azidoquinones with amines and aldehydes. Detailed mechanistic studies reveal that the EDA complex between azidoquinones and InCl3 is crucial in determining the reaction pathway. In the absence of EDA complex formation, the reaction proceeds via the intermediacy of 2,3-bridged-2H-azirine followed by regiospecific addition of an amine to CN/ring opening/cyclization to deliver p-QBZD with 1,2-azide-nitrogen migration. In the case of EDA complex formation, the reaction proceeds through regioselective aza-Michael addition/nitrene insertion with aldehyde and subsequent cyclization to deliver p-QBZD and p-quinone fused imidazole as a secondary product without 1,2-azide-nitrogen migration. This protocol provides straightforward access to redox-active quinone embedded 5-substituted-1,4-benzodiazepines from azidoquinones with diverse substrate scopes that would find potential applications in medicinal chemistry and drug discovery.

show abstract

Rapid and practical access to diverse quindolines by catalyst-free and regioselectivity-reversed Povarov reaction

Cited by 34 publications

References 66 publications

Fused-Ring-Linked Covalent Organic Frameworks

Fused-Ring-Linked Covalent Organic Frameworks

Borane-catalyzed cascade Friedel–Crafts alkylation/[1,5]-hydride transfer/Mannich cyclization to afford tetrahydroquinolines

Direct Access to Quinone-Fused 5-Substituted-1,4-Benzodiazepine Scaffolds from Azidoquinones with/without [1,2]-Azide-Nitrogen Migration: Mechanistic Insights

Contact Info

Product

Resources

About