Indole, diazepine-fused

In 2008, Fujii, Ohno and their co-workers developed an interesting method for the preparation of indole-fused 1,4-diazepines by eopper-catalyzed domino three-component coupling-indole formation-lV-aiylation. ... 

In Chap. 4, the author describes a direct access to indole-fused tetracyclic compounds containing a 1,4-diazepine framework by copper-catalyzed domino three-component coupling, cyclization, and A -arylation, which involve the formation of one carbon-carbon bond and three carbon-nitrogen bonds. 

Concise Synthesis of Indole-Fused 1,4-Diazepines through Copper(I)-Catalyzed Domino Three-Component Coupling-Cyclization- -Arylation under Microwave Irradiation... 

Indole and 1,4-benzodiazepine frameworks are useful templates for drug discovery. Indole-fused 1,4-diazepine [24-31], found in various bioactive compounds, can also be an attractive drug template. In Scheme 1, the author reported a novel... 

Carboline stmcture was constructed by one-pot reaction, which involves the three-component indole formation and nucleophilic cycUzation by the addition of t-BuOK or MsOH. This is the first example of multi-component synthesis of carbolines, except for those using the Pictet-Spengler type reaction. Utilizing the three-component indole formation, indole-fused 1,4-diazepines were also synthesized through deprotection/iV-arylation at nitrogen atom of indole by one-pot addition of MeONa after the formation of indole. These reactions form four bonds in a single reaction vessel, which involves two C-C bonds/two C—N bonds or one C-C bond/three C-N bonds. 

By use of the versatile reactivity of the copper catalysts, the Ohno group expanded their three-component indole formation (Scheme 19.78) to a one-pot synthesis of diazepine-fused indoles [152]. After formation of 2-(aminomethyl)indoles 307 using 2-ethynyl-At-mesylanilines 305, formaldehyde, and 2-bromobenzylamines 288b, addition of NaOMe furnishes removal of Ms group and spontaneous copper-catalyzed N-arylation to produce indole-fused 1,4-diazepines 308 (Scheme 19.82). 

More complex cascade processes involving this type of three-component couphng include the Cu(I)-catalyzed cascade coupling/cyclization reaction for the synthesis of 2-(aminomethyl) indoles 104 (Scheme 5.69) [72] and 105 (Scheme 5.70) [73], and the Cu(I)-catalyzed domino three-component coupling/cyclization/N-arylation reaction, which provided a concise synthesis of indole-fused 1,4-diazepines 106 (Scheme 5.71) [74]. 

SCHEME 5.71 Cu(I)-catalyzed cascade couphng/cyclization/N-arylation reaction for the synthesis of indole-fused 1,4-diazepines 106. 

Starting from simple 2-ethynylanilines 199 and o-bromobenzylamines 200, complex indole-fused 1,4-diazepines 201 were easily and directly synthesized in a single reaction vessel (Scheme 70) [115], This transformation included a sequential Cu-catalyzed three-component crmdensation/indole formation/A -aiylation process. o-Bromoheteroarylamines were also available for this domino process and various indole-fused tetracyclic compounds were obtained. 

Ohta et al. (2008) synthesized indole-fused benzo-l,4-diazepines by copper catalyzed domino three component coupling, indole formation and N-arylation under microwave irradiation from a simple N-mesyl-2-ethynylaniline at 170"C for 20-40 min. 

The susceptibility of the pyrrole ring to electrophilic attack has been used in the synthesis of pyrrolo-fused 1,4-diazepines, for example, A-(3-acetylaminopropyI)-3-methyl indole underwent a Bischler-Napierelski-type cyclodehydration on treatment with phosphorous oxychloride in benzene to give ll-methyl-4,5-dihydro-3ff-l,4-diazepine[l,2-a]indole <91IJC(B)1018>. In another example the acyl azide (143) cyclized to the furo[2,3-e]pyrrolo[l,2-a]-l,4-diazepine-9-one (144) (Scheme 25) <92JHC1507>. 

A range of indolo(triazolo)-l,4-diazepine derivatives 104 were obtained by a microwave-heated three-component reaction involving tandem N-alkylation of indole 101 with epichlorohydrin 102, ring-opening of the epoxide with azide 103, and intramolecular azide-alkyne 1,3-dipolar cycloaddition reactions (13BJO401). Fused triazolodiazepinones were obtained via azide-alkyne 1,3-dipolar cycloaddition followed by lactamization (13JHC430). 

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