Cu(I)–NHC-Catalyzed (2 + 3)-Annulation of Tetramic Acids with 2H-Azirines: Stereoselective Synthesis of Functionalized Hexahydropyrrolo[3,4-b]pyrroles

Abstract

A stereoselective and high-yield synthesis of hexahydropyrrolo[3,4-b]pyrroles from tetramic acids and 2H-azirines under Cu(I)-NHC catalysis is developed. An unusual N-C2 azirine bond cleavage, initiated by a copper enolate, was rationalized in terms of a free radical reaction mechanism.

Metal-Catalyzed and Metal-Mediated Approaches to the Synthesis and Functionalization of Tetramic Acids

“…It is noteworthy that various metals, such as Mg(II), Cd(II), Fe(III), and Ni(II), which are known to catalyze intramolecular and intermolecular transformations of azirines to ring expansion products, were tried without result. Three years later, the same group reported a Cu(I)-catalyzed (2 + 3) annulation reaction of tetramic acids 69 with 2H-azirine 70 toward hexahydropyrrolo[3,4-b]pyrrole 71 [144]. The reaction is catalyzed by Cu(II) as well, but the best results were obtained with the use of the N-heterocyclic carbene-copper(I) complex IPrCuCl (Scheme 22).…”

“…Three years later, the same group reported a Cu(I)-catalyzed (2 + 3) annulation reaction of tetramic acids 69 with 2H-azirine 70 toward hexahydropyrrolo [3,4-b]pyrrole 71 [144]. The reaction is catalyzed by Cu(II) as well, but the best results were obtained with the use of the N-heterocyclic carbene-copper(I) complex IPrCuCl (Scheme 22).…”

Catalyst‐Controlled Regioselective Synthesis of α‐Amino Oxime Esters from N‐(Acyloxy)amides and 2H‐Azirines

“…In fact, Pd 2 (dba) 3 was found to be a better catalyst because 3a was generated in 64 % yield ( Table 1, entries 7-9). Rh I and Rh III catalysts also showed low activities, but Rh II catalyst was totally inactive (Table 1, entries [10][11][12][13][14]. We further screened the effects of bases on the catalytic activity of Pd 2 (dba) 3 (Table 1, entries [13][14][15][16][17].…”

“…[10] Cu I -catalyzed stereoselective reaction of tetramic acids and 2H-azirines leading to hexahydropyrrolo [3,4-b]pyrroles proceeded through a free radical reaction mechanism initiated by N-C2 bond cleavage. [11] To date, most of the known reactions of 2H-azirines involve the formation of heterocycles. The ring-opening reaction of 2Hazirines to chain nitro-containing compounds has not been well studied.…”

A New Synthetic Route to Polyhydrogenated Pyrrolo[3,4-b]pyrroles by the Domino Reaction of 3-Bromopyrrole-2,5-Diones with Aminocrotonic Acid Esters

“…Hexahydropyrrolo[3,4- b ]indoles were obtained as a result of organocatalytic asymmetric anellation of N-hydroxymaleimides with nitrosobenzene [ 31 ]. Synthetic equivalents of C–C–N synthon are also 2 H -azirines, which form hexahydropyrrolo[3,4- b ]pyrroles in Cu-catalyzed domino-reactions with tetramic acid derivatives [ 32 , 33 ]. Oxidative cyclization of maleimides with amines and alkyne esters is also catalyzed by copper (I) salts [ 34 ] ( Scheme 1 , Route D).…”