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

Abstract

An efficient organo-photocatalytic method for the synthesis of tetrasubstituted pyrroles bearing a ketone, ester, alcohol, or nitro group at the 3-position has been developed. The reaction involves visible-light-mediated formal [3+2] dipolar cycloaddition between 2H-azirines and α-substituted nitroalkenes followed by a denitration or debromination sequence. The notable features of the protocol are excellent regioselectivity, wide substrate scope, and high yields of the products.

Bromonitroalkenes as efficient intermediates in organic synthesis

“…The reaction proceeds via [3 + 2] dipolar cycloaddition reaction, followed by the debromination sequence. 60…”

Recent advances in the synthetic applications of Morita–Baylis–Hillman and Rauhut–Currier adducts of nitroalkenes

“…Rastogi and co-workers achieved a visible light-mediated synthesis of highly functionalized pyrroles 32 by the reaction between MBH alcohols 5 and 2 H -azirines 31 (Scheme 11). 21 9-Mesityl-10-methylacridinium tetrafluoroborate (Mes-Acr + BF 4 − ) was employed as the photocatalyst for the formal [3 + 2] cycloaddition reaction of MBH alcohols 5 with 2 H -azirines 31 . Subsequent elimination of the nitro group resulted in the formation of tetrasubstituted pyrroles 32 in low to high yields.…”

Visible light-promoted synthesis of 4,6a-dihydropyrrolo[3,4-c]pyrrole-1,3(2H,3aH)-dionesvia[3+2] cycloaddition reaction of 2H-azirines with maleimides

“…5 Visible light-induced reactions using 2 H -azirines as substrates have been developed to synthesize various nitrogen-containing heterocycles (Scheme 1), such as oxazoles, 6 triazoles, 7 dihydro-oxadiazoles, 8 triazines, 9 dihydroimidazo[2,1- a ]isoquinolines, 10 benzo[ f ]isoindole-4,9-diones 11 and pyrroles. 12 Although there are many reported cyclizations of 2 H -azirines that proceed via light-induced pathways, light-induced diastereoselective transformations of 2 H -azirines remain unexplored; there are few examples of a diastereoselective transformation that proceeds via ring opening of 2 H -azirines under light irradiation. 13 The pyrrolo-[3,4- c ]pyrrole-1,3-dione moiety is an attractive scaffold that can be found in pharmacologically relevant compounds showing several different biological activities (Fig.…”