An Efficient and Diastereoselective Intramolecular 1,3‐Dipolar Cycloaddition of Cyclic Azomethine Ylides and Nitrones

Abstract

Nitrones and azomethine ylides formed by condensation of chiral 2-formyl-perhydro benzoxazines and N-substituted hydroxylamines or cyclic α-amino acids cyclize intramolecularly yielding polycyclic isoxazolidine or pyrrolidine derivatives, respectively, with total diastereoselectivity. On the con-

Ethyl 1-benzyl-1,2,3,3a,4,10b-hexahydropyrrolo[2′,3′:3,4]pyrrolo[1,2-a]benzimidazole-2-carboxylate

“…1), the benzoimidazole unit is essentially planar, with a root mean square deviation of 0.0087 Å from the nine constituent atoms. The two pyrrolidine rings have envelope forms and are cis fused, which is consistent with conventional azomethine ylide cycloadditions in similar systems (Pedrosa et al, 2006;Yang et al, 2006). However, unlike the previously reported analogues obtained from an intramolecular azomethine ylide and alkene cycloaddition tethered by an oxazolidin-2-one (Cheng et al, 2001), the ester appendage in the title structure was unambiguously assigned as cis to the angular protons H2A and H10A by X-ray crystallography.…”

“…For related literature on the pharmaceutical properties of benzimidazole and pyrrolidine, see: Gudmundsson et al (2000); Hamilton & Steiner (1997). For related literature on the azomethine ylide cycloaddition in similar systems, Pedrosa et al (2006); Yang et al (2006).…”

A novel diastereoselective 1,3-dipolar cycloaddition approach to cis-fused bispyrrolidines

“…The high stereoselection of the cycloaddition reaction could be attributed to the selective addition of the anti-dipole to the tethered alkene through an exo-approach. 26 In the 13 C NMR spectrum, the methylene carbon displayed a signal at d 34.07 and the benzylic carbon in the thiozolidine ring exhibited a signal at d 74.72. Furthermore, the structure of the cycloadduct 10e was confirmed by the mass spectrum exhibiting a molecular ion peak at m/z 570.08 (M + ).…”

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

“…Inhibitors of protein methyltransferases [9], glycosyltransferases [10], agonists of various serotonin 5-HT-receptors [11][12][13], antagonists of integrin VLA-4 [14], promising structural analogs of antibacterial fluoroquinolones [15] have been found among the derivatives of hydrogenated pyrrolo [3,4-b]pyrroles, thereby causing a significant interest in the search for new synthetic approaches to this heterocyclic system. The most common strategy for its construction from non-cyclic precursors (Scheme 1, route A) is based on a multistage synthesis of N-alkenyl tethered aldehydes, which are further subjected to intramolecular cyclization with α-amino acids via the formation of azomethine ylides [11,12,[16][17][18][19][20][21].…”

“…Hydrogenated pyrrolo [3,4-b]pyrroles are also formed as a result of intramolecular 1,3-dipolar cycloaddition in phosphorus-containing azomethine ylides generated in situ from alkene-tethered imines, acid chlorides and phosphonites [22] or transition metal promoted carbonilative [2+2+1] carbocyclization of N-allene imines [23,24]. ref [11,12,[16][17][18][19][20][21][22] ref [29,30] N N ref [10] N N ref [14] [25,26] N ref [27] N ref [28] [32] ref [33] Another direction in the synthesis of pyrrolo [3,4-b]pyrroles is the annelation of the second pyrrole ring to already existing. Examples of such examples include intramolecular amidation [10,14], alkylation [25], condensation [26], nucleophilic addition [27], Paal-Knorr heterocyclization [28] in appropriately substituted pyrroles (Scheme 1, route B).…”