Highly regio- and diastereoselective [3 + 2]-cycloadditions involving indolediones and α,β-disubstituted nitroethylenes

Abstract

Diastereoselective [3 + 2]-cycloadditions of oxindoles with α,β-disubstituted nitroethylenes: regioreversed spiropyrrolidines show potent MRSA activity.

Unveiling the high regioselectivity and stereoselectivity within the synthesis of spirooxindolenitropyrrolidine: A molecular electron density theory perspective

“…(ii) The formation of cycloadduct 10 with C1-C4 and C3-C5 bonding regiochemistry and trans stereochemical disposition of the nitro and indolinone substituents on the C1 and C4 carbons is theoretically predicted via TS1 presenting the lowest activation energy among the four possible reaction paths both in gas phase and in methanol. The activation enthalpy of TS1 is lowered by 5.1, 3.5 and 7.7 kcal mol −1 in gas phase and by 3.4, 6.3 and 9.3 kcal mol −1 in methanol relative to TS2, TS3 and TS4, respectively, suggesting complete regioselectivity and stereoselectivity in clear agreement with the experimental results [42] showing generation of spirooxindolepyrrolidine adduct 10 as the major product. (iii) A reasonably low activation enthalpy of 1.0 kcal mol −1 in gas phase and 1.9 kcal mol −1 in methanol is calculated for the 32CA reaction of AZY 8 with BNS 9 leading to cycloadduct 10 via TS1, which agrees with the polar character of the reaction and pseudodiradical electronic structure of AZY 8 (Section 3.1).…”

“…Thus, favourable two-centre interaction along the polar process is predicted between the C3 carbon of AZY 8 and C5 carbon of BNS 9, in agreement with the experimentally observed regioselectivity. [42] 3.3 | Analysis of the PES of the 32CA reaction between AZY 8 and BNS 9…”

“…We hereby present a detailed MEDT study at B3LYP/6-31G(d) level of theory for the highly regioselective and stereoselective synthesis of spirooxindole-pyrrolidine derivative from 32CA reactions of isatin 6 and N-Me glycine 7 (involving in situ generation of the azomethine ylide AZY 8) with (E)-1-bromo-1-nitrostyrene BNS 9 experimentally realised by Rao et al in 2019 (Scheme 4). [42] It is worth to note that AZY 8 involves primary carbanion as the TAC, whereas azomethine ylide 4 (Scheme 3) involves the participation of secondary carbanion in the 32CA reaction. The reagents isatin 6, N-Me glycine 7 and (E)-1-bromo-1-nitrostyrene BNS 9 were heated in methanol with 70% conversion and the spirooxindolenitropyrrolidine isomer 10 was obtained as the major product.…”

“…The reactions were also inferior in DMSO, DMF, THF and CCl 4 . [42] The B3LYP/6-31G(d) computational level has been applied to successfully understand the selectivity and mechanism of several recent 32CA reactions, [34,[43][44][45][46][47] which justifies its applicability in the present MEDT study.…”

α‐Iodonitroalkenes as Potential Antifungal and Antitubercular Agents

“…In a quest to unleash the properties of halogen and nitro groups, we had earlier synthesized α‐bromonitroalkenes and applied in the cross‐coupling chemistry . Further, its extended work on the synthesis of bioactive spirooxindoles has been reported by us . The antibacterial and antineoplastic properties of halogenonitro olefins were formerly documented in non‐english journals .…”