Pyrrolo isoquinolin-3-ones

In a recent example, Mironov used the rational replacement of starting materials for oligomerization reactions to discover new MCRs in a systematic way [31]. A reaction library of six alkenes/alkynes, two isonitriles, two nitriles and isoquinoline was set up, giving (n1 — n)/2 different reactions products. A minimum peak height of 30% of the total reaction product was used as a criterion for identifying an efficient MCR. In this way, a novel MCR that yields pyrrolo[2,l-a]isoquinolin-1-ones from electron-deficient olefins, isonitriles and isoquinoline was found (Scheme 10.6). 

The fully-unsaturated 1,3-benzodiazepine 310 is formed by a photoreaction of the 1-substituted isoquinoline 7V-imide 309 (Scheme 169) <1980CPB2602>. The same principle has been applied to prepare thieno-, furo-, and pyrrolo-fused 1,3-diazepines <1980CC454, 1981CPB1539>. The imidazolo-fused l,3-benzodiazepin-2-ones 313 can be prepared by the reaction of 5-amino-4-(cyanoformimidoyl)imidazoles 311 with tosyl isocyanate. The mechanism of this reaction includes a 1-exo-dig cyclization of intermediates 312 followed by a Dimroth rearrangement to give the thermodynamic products 313 (Scheme 170) <1996JHC855, CHEC-III(13.05.9.2.2)174>. 

The two-step one-pot total synthesis of Ro 22-1319, an antipsychotic agent featuring a rigid pyrrolo[2,3-g]isoquinoline skeleton, was accomplished by D.L. Coffen and co-workers. The cyclic 1,3-diketone precursor was prepared from arecoline and dimethyl malonate, and in the same reaction vessel an amino ketone hydrochloride was added. The pH of the reaction mixture was adjusted to 4 in order to initiate the formation of the pyrrole. 

Pyrolysis of suitably 3-substituted benzotriazinones 19 provides access to various fused heterocycles. Thus, pyrolysis of 19j at 250°C gives l,3-diphenyl-277-pyrrolo[3,4-f]isoquinolin-5-one 69 <1992JHC1309>, and a multistep sequence transforms 19k into the dione 70 <1982JCM295>. 

This methodology with some variations has been utilized in the synthesis of numerous heterocyclic systems, such as heterocycle-fused quinolinone derivatives [391], l,4-benzodiazepin-2-ones [392], benzo-, naphtho- and heterocycle-fused pyrrolo[2,l-c][l,4]diazepines [393], quinolinone or pyrrolidinone derivatives [394], dibenzo[fl,c]phenanthridines [395], thiazolo-fused quinolinones [396], isoindolinone and isoquinolin-2-one derivatives [397], indoline derivatives [398], 5-aroyl-pyrrolidinones [399,400], indazolone derivatives [401,402], substituted indolizidinones [403], 1-arylpyrrolopyrazinones [404], stmcturally diverse... 

One important visible-light-induced C-H oxidation/[3 + 2] cycloaddition/ oxidative aromatization tandem sequence was developed by Xiao and co-workCTS in 2011, allowing for concise synthesis of pyrrolo[2,l-a]isoquinolines (Scheme 3.7) [35]. 

Martinez R, Arzate MMT, Ramirez-Apan M (2009) Synthesis and cytotoxic activity of new azepino [3, 4 4, 5] pyrrolo [2, 1-a] isoquinolin-12-ones. Biootg Med Chem 17 1849-1856... 

SCHEME 18 One-pot three-component reaction of variously substituted isoquinolines, 2-bromoacetophenone, and N-arylmaleimide derivatives to form tetrahydropyrrolo-[3, 4 3.4]pyrrolo[2.1-fl]isoquinoline-9,ll-diones. 

Monsal and coworkers have achieved the construction of pyrrolidine nucleus in the synthesis of tetrahy-dropyrrolo[3, 4 3.4]pyrrolo[2.1-fl]isoquinoline-9,ll-diones 57 derivatives in an aqueous micellar medium [53]. The S5mthesis involves a one-pot three-component reaction of variously substituted isoquinolines 54, 2-bromoacetophenone 55, and N-arylmaleimide derivatives 56 in the presence of triethylamine as a base (Scheme 18). The preliminary investigation indicated that the presence of surfactant was essential for the success of reaction. Accordingly, the reactions were carried out in cationic, anionic, and nonionic surfactants well above their critical micelle concentrations (CMC). The maximum yields were obtained in cetyltrimethylammonium bromide (CTAB) (CTABiCMC value 0.29 mM at 80mM concentration). The mechanism of formation involves an in situ generation of isoquinolinium ylides followed by [2 -h3] cycloaddition of N-aryl maleimides. 

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