First synthesis of fused-Δ¹-pyrrolines via intramolecular 1,3-dipolar cycloaddition of ketoimine: A complete diastereoselective approach

Abstract

Intramolecular formal 1,3-dipolar cycloaddition of ketoimine is developed with PhIO for the first synthesis of fused-Δ(1)-pyrrolines. The scope of the reaction, complete diastereoselectivity and its rationalization by a computational study are reported.

Recent Advances in Iodosobenzene‐Mediated Construction of Heterocyclic Scaffolds: Transition‐Metal‐Free Approaches and Scope

“…In contrast to aldimine dimerisation, the ketoimine counterpart showed completely different fate upon treatment with PhIO . On treating the ketoimine 108 with PhIO, intramlecular cycloaddition led to cis‐cis isomer 109 (Scheme ).…”

Diastereoselective Nucleophilic Ring‐Opening Reactions of 2,6‐Diazasemibullvalenes for the Synthesis of Diverse Functionalized Δ1‐Bipyrroline Derivatives

“…1 H NMR (300 MHz, CDCl 3 , 258C, TMS): d = 1.22 (s, 9 H; CH 3 ), 1.25-1.26 (m, 5 H; CH 2 ), 1.33 (s,9 H;CH 3 ), 2.06-2.10 (m, 2 H; CH 2 ), 2.82-2.94 (m, 3 H; CH 2 ), 5.06 (s, 1 H; CH), 6.98-7.09 (m, 2 H; C 6 H 5 ), 7. 10-7.26 (m, 4 H; C 6 H 5 ), 7.37-7.42 ppm (m, 4 H; C 6 H 5 ); 13 C NMR (75 MHz, CDCl 3 , 258C, TMS): d = 18.37, 19.36, 26.95, 28.08, 29.16, 35.31, 36.07, 35.62, 44.49, 77.84, 79.51, 83.58, 121.47, 121.55, 122.16, 123.05, 128.54, 128.84, 147.31, 151.09, 180.30, 181.97 Nucleophilic ring opening of 1 a with N-methylindole in the presence of lanthanum triflate Compound 1 a (0.5 mmol, 136 mg) in toluene (2 mL) was treated with N-methylindole (0.6 mmol, 79 mg) and lanthanum triflate (0.05 mmol, 30 mg). The reaction mixture was stirred at 50 8C for 12 h. The solvent was evaporated under vacuum to give yellow oil, which was purified by column chromatography (silica gel, petroleum ether/diethyl ether/triethylamine = 100:5:1) to afford 11 as a colorless solid (93 %, 187 mg).…”

“…Diverse functionalized D 1 -bipyrroline derivatives were obtained in good yields with high regio-and diastereoselectivity. D 1 -Bipyrroline derivatives, [13] because of their unique N-containing fused-ring structures, are useful building blocks for biologically relevant compounds and important synthetic intermediates for organic synthesis. However, synthetic methods for D 1 -bipyrroline derivatives are very limited.…”

“…However, synthetic methods for D 1 -bipyrroline derivatives are very limited. [13] Results and Discussion Nucleophilic ring opening of 2,6-diazasemibullvalenes with neutral proton-containing nucleophiles: diastereoselective synthesis of functionalized D 1 -bipyrroline derivatives A wide variety of proton-containing nucleophiles were applied to react with NSBVs 1 under mild reaction conditions (Scheme 2). Nucleophilic ring-opening reactions of NSBVs 1 took place smoothly to afford functionalized D 1 -bipyrroline derivatives 2-10 in good-to-excellent isolated yields with excellent diastereoselectivity.…”

Metal-mediated synthesis of pyrrolines

“…[24][25][26][27][28][29][30][31][32][33][34][35][36][37] A variety of well-established methods of pyrrolines synthesis are available. 38,39 These methods include intramolecular cyclizations of bifunctional compounds and multi-component cyclizations, [39][40][41][42][43][44][45] 1,3-dipolar cycloadditions, [46][47][48][49][50][51] photo-and thermoinduced reactions, [52][53][54] and ring expansion of aziridines, 55,56 among others. However, metal-mediated syntheses have emerged as a valuable complement to these methods 20,57,58 due to their high atom economy, their mild reaction conditions, and the high functional group tolerance of the transition metalcatalyzed reactions.…”