Intramolecular 1,3-dipolar cycloaddition reactions in the synthesis of complex annelated quinolines, α-carbolines and coumarins

Abstract

In this study, we report the synthesis of several novel dihydroisoxazole-, tetrahydroisoxazole- and dihydropyrazole-fused pyrido[2,3-b]quinolines, α-carbolines, and pyrido[2,3-c]coumarins, respectively, from simple precursors and by exploring intramolecular 1,3-dipolar cycloaddition reactions involving nitrile oxides, nitrones, and nitrile imines as 1,3-dipoles.

Unveiling the intramolecular [3 + 2] cycloaddition reactions ofC,N-disubstituted nitrones from the molecular electron density theory perspective

“…In 2017, tricyclic fused isoxazolidines were synthesized regioselectively from the IM32CA reactions of 1,1,1,-trifluoromethyl styrene derived nitrones 17 and recently, in 2020, Bakthados and Mushaf 18 have reported the IM32CA reactions of nitrone 13 generated from substituted o-allyl salicylaldehyde 12 for the synthesis of complex bicyclo [3.2.1] scaffolds 14 (Scheme 2). The IM32CA reactions of nitrones have been experimentally studied by numerous synthetic chemists [7][8][9][10][11][12][13][14][15][16][17][18] as a well established synthetic strategy for fused isoxazolidines. However, the theoretical implications of these reactions still remain a cornerstone relative to those addressing intermolecular 32CA reactions.…”

Coumarin heterocyclic derivatives: chemical synthesis and biological activity

“…202 A related more recent example of such reactivity was reported by Bhuyan and coworkers, allowing general access to dihydroisoxazolo[3 0 ,4 0 :4,5]pyrido [2,3-c]coumarin 280 via an intramolecular 1,3-dipolar cycloaddition, involving nitrile oxides as 1,3-dipoles (Scheme 87). 203 An efficient three-component synthesis of 2,3-dihydrochromeno [4,3-d]pyrazolo[3,4-b]pyridine-1,6-diones 282 from 3-aminopyrazol-5-ones 281, salicylic aldehydes 16 and acetylacetic ester 17, involving an in situ formation of 3-acetylcoumarins and subsequent condensation with aminopyrazolones 281, has been described by Frolova and co-workers (Scheme 88). 204 A similar strategy was developed for the synthesis of 3-(4-alkyl-4,5-dihydropyrrolo[1,2-a]quinoxalin-4-yl)-2H-chromen-2-one derivatives 284, using piperidine-iodine as a dual system catalyst (Scheme 89).…”

Hydrazones as substrates for cycloaddition reactions

“…280 However, such reaction are often characterized by simultaneous formation of two five-membered rings 282 ± 284 or combinations of six-and five-membered rings. 281,285 For example, heating cis-alkene 206 at reflux in toluene affords dihydropyrazolobenzoxazines 208 via intermediate nitrile imine 207 in a good yield (Scheme 86). 281 Conversely, heating trans-alkene 206 under the same conditions yields benzoxadiazine 209 as the major product (Scheme 87).…”