Oxindole‐chromones C3 Synthons Directed Stereocontrolled Construction of Five Contiguous Stereocenters on Spiro[tetrahydrocyclopenta[b]chromanone‐oxindole]s

Abstract

The first example of bifunctional oxindole‐chromone C3 synthon directed organocatalytic cascade cycloaddition reaction is developed, serving as a fruitful strategy for the facile access of optically active tetrahydrocyclopenta[b]chromanone bearing one spirooxindole with five contiguous stereocenters. All the products are smoothly obtained with up to 83% yield, >20:1 d.r. and >99% ee. This is also the first asymmetric catalytic construction of tetrahydrocyclopenta[b] chromanone and tetrahydrocyclopenta[b]chromanone‐spirooxindole scaffold, thus to facilitate the search for new bioactive entities.magnified image

Recent advances in the synthesis of 4H-chromen-4-ones (2012 − 2021)

“…342 N-t-butyloxycarbonyl (Boc) oxindole-4H-chromen-4ones were synthesized via a four-step sequence, all at room temperature: (i) aldol reaction of isatins with chroman-4-ones mediated by diethylamine in ethanol; (ii) O-protection with MsCl in the presence of triethylamine in dichloromethane; (iii) N-protection using DMAP and (Boc) 2 O in dichloromethane; and (iv) double-bond migration carried out in triethylamine in dichloromethane. 343 A series of N-arylated pyrazol-3-yl-4H-chromen-4-ones was prepared via aldol condensation of N-arylpyrazolones with chroman-4-ones catalyzed by diethylamine in methanol, subsequent O-protection of the intermediates with MsCl in dichloromethane and finally elimination and [1,5]-proton transfer in triethylamine to afford the desired products (Scheme 54). 344 The synthesis of sulfone-containing 3-(indane-1,3-dion-2-yl)-4Hchromen-4-ones were accomplished through methanesulfonylation reaction of indanedione-chroman-4-one hybrids with methanesulfonyl chloride and triethylamine in dichloromethane at room temperature (Scheme 55).…”

Tandem 1,6-addition/cyclopropanation/rearrangement reaction of vinylogous para-quinone methides with 3-chlorooxindoles: construction of vicinal quaternary carbon centers

“…14 As such, the study of efficient procedures for the synthesis of spirocyclopentane oxindoles with rich structural diversity and complexity has attracted growing attention from numerous researchers. Regardless of the transition-metal catalyzed intramolecular coupling reaction of 2-substituted- N -phenylacrylamides 15 and other intramolecular cyclization approaches to spirocyclopentane oxindoles, 16 great effort has been focused on the intermolecular construction pathway to develop novel synthons for the construction of the core cyclopentane ring, such as spirocyclopropane oxindoles, 17 3-methyleneoxindoles, 18 3-vinyloxindoles, 19 3-allyloxindoles, 20 and other types of oxindole. 21 Despite the great progress, 3-halooxindoles, 22 a unique class of C1 synthons with pronounced reactivities, are still unexplored to date for the synthesis of the remarkable spirocyclopentane oxindole architecture (Scheme 1b).…”

Enantioselective Synthesis of Spirocyclopentane Oxindoles Bearing Five Consecutive Stereocenters through Secondary Amine‐Catalyzed [3+2] Cycloaddition

“…[9] In a report published by Liu and co-workers in 2019, quinidine-derived thiourea-catalyzed [3 + 2] annulation between C3-saturated oxindoles and nitroolefins has successfully led to the formation of cyclopentane-spirooxindoles with five contiguous chiral centers (Scheme 1b). [10] Soon afterward, the group of Lin reported an [3 + 2] cyclization between alkylidene oxindole derivatives and 3-homoacylcoumarins to give the enantioen- riched spirocyclopentane oxindoles in the presence of quininederived squaramide catalyst (Scheme 1c). [11] It is worth noting that the above-mentioned synthetic advancements were explored based on bifunctional hydrogenbonding catalysis, organocatalytic cascade reactions using other covalent catalysis are currently less explored and highly desirable in assembling such spiro architectures with five contiguous chiral centers.…”

“…In 2016, Du's group employed electron‐deficient methyleneoxindoles as substrates to react with α‐alkylidene succinimide derivatives through a bifunctional squaramide‐promoted double Michael addition, which realized the asymmetric synthesis of spirocyclopentane oxindoles (Scheme 1a) [9] . In a report published by Liu and co‐workers in 2019, quinidine‐derived thiourea‐catalyzed [3+2] annulation between C3‐saturated oxindoles and nitroolefins has successfully led to the formation of cyclopentane‐spirooxindoles with five contiguous chiral centers (Scheme 1b) [10] . Soon afterward, the group of Lin reported an [3+2] cyclization between alkylidene oxindole derivatives and 3‐homoacylcoumarins to give the enantioenriched spirocyclopentane oxindoles in the presence of quinine‐derived squaramide catalyst (Scheme 1c) [11] …”