Visible Light‐Induced, Metal‐Free Denitrative [3+2] Cycloaddition for Trisubstituted Pyrrole Synthesis

Abstract

Am etal-free, regioselective synthesis of trisubstituted pyrroles has been developed throughaformal [3+ +2] cycloaddition reactionb etween 2H-azirines and nitroalkenes under visible light/photoredox-catalyzedc onditions. The re-action proceeds through 2H-azaallenyl radical addition on bnitrostyrenes in aM ichael fashion followed by ab ase-mediated denitration reaction. The directive group influence of the nitro group controlst he regiochemistry of the reaction.

Organo-photocatalytic Synthesis of Functionalized Pyrroles from 2H-Azirines and α-Substituted Nitroalkenes

“…2 Recent progress in the field of visible-light-mediated heterocycle synthesis 3 has inspired the discovery of several elegant protocols for the synthesis of pyrrole derivatives, including organometallic photocatalyst-mediated protocols such as the Hantzsch synthesis of 2,5-diaryl-substituted pyrroles, 4 the Paal–Knorr type synthesis of 1,3,4-trisubstituted pyrroles via condensation of aryl azides with aldehydes, 5 and the synthesis of the 2,3-fused pyrrole motif via coupling of naphthols and naphthoquinones with 2 H -azirines. 6 Moreover, strategies employing organic dyes as photocatalysts for the synthesis of thio-functionalized pyrroles 7 and tetra-/trisubstituted pyrroles through formal [3+2] cycloaddition of 2 H -azirines with alkynes 8 or nitroalkenes 9 have been reported. Our group recently employed pyrylium salts in a dual role as a photosensitizer and dipolarophile in the dipolar cycloaddition with 2 H -azirines for accessing chalcone-bearing tetrasubstituted pyrroles.…”

“…Herein we present an extension of our previous work 9 utilizing α-substituted nitroalkenes as dipolarophiles in organo-photocatalytic formal [3+2] cycloadditions with azirines to prepare tetrasubstituted pyrroles (Scheme 1 ).…”

“…9-Mesityl-10-methylacridinium tetrafluoroborate (Mes-Acr + BF 4 – ; PC-I ) was employed as the photocatalyst after consideration of the thermodynamic feasibility of the single-electron transfer between PC-I and 1a , owing to their compatible redox potentials (Table 1 ). 8 9…”

Strain Release Chemistry of Photogenerated Small‐Ring Intermediates

“…Although the authors did not incorporate the photogeneration of azirine 60 in succeeding studies, several other groups were able to extend the demonstrated methodology to other reaction partners furnishing oxazoles, [26] 2‐acyloxazoles, [27] 2,5‐dihydro imidazoles, [26] 2,5‐dihydroisoxazoles, [28] 1,2,4‐triazoles [29] and 2,4,5‐trisubstituted pyrroles [30] …”

Redox-Neutral 1,3-Dipolar Cycloaddition of 2H-Azirines with 2,4,6-Triarylpyrylium Salts under Visible Light Irradiation

“…Recently, our group also successfully applied the same approach for the regioselective synthesis of trisubstituted pyrroles employing nitroalkenes as dipolarophiles . Evidently, in both the reactions, the high oxidation potential of 2 H -azirines warrants the usage of a strongly oxidizing acridinium photocatalyst for the photocatalytic cleavage of the azirine ring, generating an azaallenyl radical cation intermediate (Scheme a). , …”