Bismuth(III)-Catalyzed 1,8-Addition/Cyclization/Rearrangement of Propargylic para-Quinone Methides with 2-Vinylphenol: Synthesis of Indeno[2,1-c]chromenes

Abstract

The unique reactivity of in situ generated propargylic paraquinone methides as a new type of five-carbon synthon has been discovered by a novel bismuth(III)-catalyzed tandem annulation reaction. This 1,8-addition/ cyclization/rearrangement cyclization cascade reaction is characterized by unusual structural reconstruction of 2-vinylphenol, involving cleavage of the C1′�C2′ bond and formation of four new bonds. This method provides a convenient and mild approach to generate synthetically important functionalized indeno[2,1-c]chromenes. The mechanism of the reaction is proposed from several control experiments.

Acid-Mediated Cascade Cyclization Pathway to Indeno[2,1-c]chromen-6(7H)-ones

“…1−9 For instance, tetracyclic brazilin, brazilane, brazilein A, (±)-pestalachloride C, and (±)-pestalachloride D exist in nature (Figure 1). 10 Specifically, brazilin displays a series of biological and pharmacological activities, including anti-inflammatory, 11 anticancer, 12−14 neuroprotective, 15,16 hypoglycemic, 17,18 and vasorelaxant 19 activities, while the indano[2,1-c]chromans (+)-hematoxylin and (−)-brazilein A show tissue staining and immunosuppressive activities, respectively. 4 For instance, the Lewis/Brønsted acid-mediated cascade or domino organic transformation reaction for synthesizing valuable carbocyclic and heterocyclic organic frameworks from reasonably simple starting materials is a powerful tool in organic chemistry.…”

“…Indene and chromene skeletons and their fused tetracyclic framework are an essential core in many natural products, biologically and pharmacologically active molecules, and those that are relevant to material science. − For instance, tetracyclic brazilin, brazilane, brazilein A, (±)-pestalachloride C, and (±)-pestalachloride D exist in nature (Figure ). Specifically, brazilin displays a series of biological and pharmacological activities, including anti-inflammatory, anticancer, − neuroprotective, , hypoglycemic, , and vasorelaxant activities, while the indano­[2,1- c ]­chromans (+)-hematoxylin and (−)-brazilein A show tissue staining and immunosuppressive activities, respectively …”

“…Subsequently, the Yang group in 2020 explored a Pd-catalyzed intramolecular cyclization of 3-benzoyl-substituted coumarins that afforded the indeno­[2,1- c ]­chromen-6,7-diones (Scheme b). Recently, in 2023, Zhu and co-workers disclosed a Bi-catalyzed cascade cyclization protocol for the synthesis of indeno­[2,1- c ]­chromenes through a 1,8-addition/cyclization and rearrangement sequence of in situ -generated propargylic p -quinone methides with 2-vinylphenols (Scheme c). In another report, the research group of Yang, unveiled a stepwise route for synthesizing a few indeno­[2,1- c ]­chromen-6­(7 H )-ones through Pd-catalyzed intramolecular Heck coupling (Scheme d).…”

Rapid Assembly of Functionalized 2H-Chromenes and 1,2-Dihydroquinolines via Microwave-Assisted Secondary Amine-Catalyzed Cascade Annulation of 2-O/N-Propargylarylaldehydes with 2,6-Dialkylphenols

“…14 Furthermore, indeno [2,1-c]chromene is an attractive tetracyclic skeleton owing to its existence in various natural products with a broad spectrum of biological applications exemplified by brazilin VI. 15 Although a considerable number of synthetic methodologies have been established for the synthesis of 2H-chromenes, 16 1,2-dihydroquinolines, 17 and indeno [2,1-c]chromenes, 18 the development of rapid and operationally simple synthetic strategies to achieve these valuable heterocycles bearing additional functionalities remains an essential task. Furthermore, p-quinone methides (p-QMs) are important and widely useful electrophilic structural fragments that are frequently employed to access structurally diverse molecules.…”

Synthesis of Indenone-Fused Pyran Derivatives from Aryl Enaminones and Cyclopropenones through Unsymmetrical Relay C–H Bond Activation and Double C–C/C–O Bond Formation

“…Given the importance of both indenone and pyran moieties, it is reasonable to deduce that hybrid compounds containing these two privileged scaffolds might be endowed with unique physical, chemical, and biological properties. To date, while numerous methods for the respective preparation of indenone and pyran derivatives have been well-developed, reliable protocols for the construction of indenone-fused pyran skeletons are still rare . Therefore, the development of effective and concise methods for this purpose constitutes an urgent task for the synthetic and medicinal community.…”