Synthesis of Pyrrolo[1,2-a]quinoxaline Derivatives by Lewis Acid-Catalyzed Reactions of 1-(2-Isocyanophenyl)pyrroles

Abstract

1-(2-Isocyanophenyl)pyrroles have been prepared. They react in moderate to good isolated yields with aldehydes (or ketones), oxiranes, and acetals in the presence of catalytic amounts of diethyl ether–boron trifluoride to give pyrrolo[1,2-a]quinoxalines carrying an oxyalkyl substituent, such as α-hydroxyalkyl, β-hydroxyalkyl, or α-alkoxyalkyl, at the 4-position.

A one-pot catalyst-free synthesis of functionalized pyrrolo[1,2-a]quinoxaline derivatives from benzene-1,2-diamine, acetylenedicarboxylates and ethyl bromopyruvate

“…Recently, Patil et al developed the PtBr 2 and Au(I)-catalyzed hydroamination–hydroarylation cascade reactions of 2-(1 H -pyrrol-1-yl)anilines with alkynes to form 4,5-dihydropyrrolo[1,2- a ]quinoxalines [23–24]. Kobayashi and co-workers have described the Lewis acid catalyzed cyclization of 1-(2-isocyanophenyl)pyrroles to give pyrrolo[1,2- a ]quinoxalines in good yields; however, the isocyanide substrates required multistep synthesis [25–26]. Ma and Yuan have reported the synthesis of pyrrolo[1,2- a ]quinoxalin-4(5 H )-ones by CuI/L-proline-catalyzed coupling of N -trifluoroacetyl-2-haloanilines with methyl pyrrole-2-carboxylates [27].…”

Pyrrolo[1,2-a]quinoxalines based on pyrroles (Review)

“…i 1 a R = H, b R = Me; 3 a-e R 2 = H, a R 1 = Et, b R 1 = 2-Pr, c R 1 = CMe 2 Et, d R 1 = Ph, е R 1 = 2-furyl; f R 1 = R 2 = Me; g R 1 +R 2 = (CH 2 ) 6 ; h R 1 = Ph, R 2 = Me; i R 1 = Me, R 2 = CO 2 Et; j R 1 = Me, R 2 = (CH 2 ) 2 CO 2 Et; 4 a R = R 2 = H, R 1 = R 3 = Me; b R = R 2 = H, R 1 = Me, R 3 = Et; c R = H, R 1 = R 2 = Me, R 3 = Et, d R = R 2 = H, R 1 = vinyl, R 3 = Et, e R = R 2 = H, R 1 = Ph, R 3 = Me; f R = R 1 = Me, R 2 = H, R 3 = Et; 9 a R = R 1 = R 2 = H, R 3 = Me; b R = R 1 = R 2 = H, R 3 = Ph; c R = R 3 = H, R 1 +R 2 = (CH 2 ) 4 ; d R = R 1 = R 2 = H; R 3 = (CH 2 ) 2 CH=CH 2 ; e R = Me, R 1 +R 2 = (CH 2 ) 4 , R 3 = H; 10 a R = H, b R = Me a POCl 3 /Et 3 N mixture in THF. The reaction takes place in the presence of catalytic amounts of boron trifluoride etherate under mild conditions (CH 2 CH 2 , 0°C), resulting in the formation of unsubstituted pyrrolo[1,2-a]quinoxaline (2) with an almost quantitative yield [2,3]. The cyclization of compound 1 catalyzed by boron trifluoride etherate also goes well in the presence of various aldehydes and ketones [2,3], semiacetals [2], and 2,5-diethoxytetrahydrofuran [2] and by the action of various epoxides [2]; here, various derivatives of pyrrolo[1,2-a]quinoxalines 2-5, 7, and 9 substituted at position 4 are formed with yields of 3-97%, depending on the employed carbonyl component [2,3].…”

“…The reaction takes place in the presence of catalytic amounts of boron trifluoride etherate under mild conditions (CH 2 CH 2 , 0°C), resulting in the formation of unsubstituted pyrrolo[1,2-a]quinoxaline (2) with an almost quantitative yield [2,3]. The cyclization of compound 1 catalyzed by boron trifluoride etherate also goes well in the presence of various aldehydes and ketones [2,3], semiacetals [2], and 2,5-diethoxytetrahydrofuran [2] and by the action of various epoxides [2]; here, various derivatives of pyrrolo[1,2-a]quinoxalines 2-5, 7, and 9 substituted at position 4 are formed with yields of 3-97%, depending on the employed carbonyl component [2,3].…”

“…However, during the production of pyrrolo-1,4-benzodiazepines by the insertion of carbon monoxide into 2-[N-R-N-(2-bromophenyl)aminomethyl]pyrrolidines 51 in the presence of catalytic amounts of Pd(OAc) 2 and PPh 3 pyrrolo[1,2-a]quinoxalines 54 were found together with other products formed as a result of the migration of, for example, an acyl group from the aniline nitrogen atom to the pyrrolidine nitrogen atom [27]. The structure and the mechanism of formation of the pyrroloquinoxaline 54 in this reaction were partly clarified by realizing closure of the ring in compound 51 in an atmosphere of argon in the absence of carbon monoxide.…”

“Multi-component Reactions : Emerging Chemistry in Drug Discovery” ‘From Xylocain to Crixivan’

“…The preparation of medicinally relevant [33] pyrrolo[1,2-α]quinoxaline derivatives 26 by Lewis acid catalyzed reactions of 1-(2-isocyano) pyrroles 25 has recently bee reported by Kobayashi [34]. Interestingly, the ortho substituted pyrrole may be viewed as a carboxylic acid equivalent, which traps the hydroxy-nitrilium ion intermediate, Scheme 5.…”