Straightforward Regio- and Diastereoselective Synthesis, Molecular Structure, Intermolecular Interactions and Mechanistic Study of Spirooxindole-Engrafted Rhodanine Analogs

Abstract

Straightforward regio- and diastereoselective synthesis of bi-spirooxindole-engrafted rhodanine analogs 5a–d were achieved by one-pot multicomponent [3 + 2] cycloaddition (32CA) reaction of stabilized azomethine ylide (AYs 3a–d) generated in situ by condensation of L-thioproline and 6-chloro-isatin with (E)-2-(5-(4-chlorobenzylidene)-2,4-dioxothiazolidin-3-yl)-N-(2-morpholinoethyl)acetamide. The bi-spirooxindole-engrafted rhodanine analogs were constructed with excellent diastereo- and regioselectivity along with high chemical yield. X-ray crystallographic investigations for hybrid 5a revealed the presence of four contiguous stereocenters related to C11, C12, C19 and C22 of the spiro structure. Hirshfeld calculations indicated the presence of many short intermolecular contacts such as Cl...C, S...S, S...H, O...H, N...H, H...C, C...C and H...H interactions. These contacts played a very important role in the crystal stability. The polar nature of the 32CA reaction was studied by analysis of the conceptual DFT reactivity indices. Theoretical study of this 32CA reaction indicated that it takes place through a non-concerted two-stage one-step mechanism associated with the nucleophilic attack of AY 3a to the electrophilic ethylene derivative.

A Molecular Electron Density Theory Study of the [3+2] Cycloaddition Reaction of Pseudo(mono)radical Azomethine Ylides with Phenyl Vinyl Sulphone

“…The intrinsic reaction coordinate (IRC) paths [30] were obtained to establish Thus, the 32CA reaction of AY 21, generated in situ from the reaction of 6-chloroisatin 18 and L-proline 19, with phenyl vinyl sulphone 20 yielded the spirooxindole 23 with total meta regio-and endo stereo-selectivities (see Scheme 5) [25]. Very recently, Barakat et al have experimentally studied a series of 32CA reactions of AYs 14, obtained in situ from isatin derivatives and secondary amines, with different ethylene derivatives 15, in the synthesis of spirooxindoles 16 and 17, with high regio-and stereoselectivity (see Scheme 4) [22][23][24]. While these 32CA reactions were endo stereoselective, the regioselective formation of spirooxindoles 16 or 17 was found to be dependent on the substitution on the ethylene derivative 15.…”

“…Scheme 3. Cb-type 32CA reactions of fluorinated AY 11.Very recently, Barakat et al have experimentally studied a series of 32CA reactions of AYs 14, obtained in situ from isatin derivatives and secondary amines, with different ethylene derivatives 15, in the synthesis of spirooxindoles 16 and 17, with high regio-and stereoselectivity (see Scheme 4)[22][23][24]. While these 32CA reactions were endo stereoselective, the regioselective formation of spirooxindoles 16 or 17 was found to be dependent on the substitution on the ethylene derivative 15.…”

Synthesis and Structure Elucidation of Novel Spirooxindole Linked to Ferrocene and Triazole Systems via [3 + 2] Cycloaddition Reaction

“…The chemical architecture was assigned, based on single-crystal X-ray-diffraction analysis and a set of spectroscopic tools, including NMR and IR spectra. The plausible mechanism is depicted in Scheme 2, based on the previously reported literatures [33][34][35][36][37][38][39].…”

[3+2] Cycloaddition Reaction for the Stereoselective Synthesis of a New Spirooxindole Compound Grafted Imidazo[2,1-b]thiazole Scaffold: Crystal Structure and Computational Study

“…1 H NMR (400 MHz, CDCl 3 ) δ 8.74 (s, 1H), 7.55-7.16 (m, 14H), 7.14 (d, J = 5.0 Hz, 1H), 6.98 (d, J = 8.0 Hz, 1H), 6.76 (s, 1H), 4.88 (q, J = 7.6 Hz, 1H), 4.15 (d, J = 9.0 Hz, 1H), 3.76 (d, J = 5.9 Hz, 1H), 3.58 (d, J = 5.9 Hz, 1H), 2.96 (dd, J = 9.8, 5.5 Hz, 1H), 2.84-2.73 (m, 1H); 13 ). The transition states were proposed to afford the only regioisomer and diastereoisomer based on the recent literature [19][20][21][22]24] (Scheme 2). The chemical feature of the bis-spiro compound 4 was assigned based on 1 H-NMR, 13 C-NMR, IR and single-crystal X-ray diffraction analysis.…”