Isatin N-protected ketimines with nitromethane catalyzed by chiral binol linked monomeric macrocyclic Cu(II)–salen complex. Issue 49 (6th December 2018)

• Record Type: Journal Article
• Authors: Menapara, Tusharkumar; Tak, Raj kumar; Saravanan, S.; Kureshy, Rukhsana I.; Khan, Noor-ul H.; Ganguly, B.; Si, Mrinal Kanti
• Is Part Of: Tetrahedron. Volume 74:Issue 49(2018)
• Page Start: 7000
• Page End: 7008
• Publication Date: 2018-12-06
• Subjects: Asymmetric aza-Henry -- Cu(II) -- Macrocyclic ligand -- Recyclability -- (S)-Diamine; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2018.10.001
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: ChiralCu-1B generated in situ was used as an efficient catalyst for the synthesis of β -nitroamines in high yield (88%) with excellent enantioselectivity (ee up to 99%) at RT in absence of co-catalyst via asymmetric aza-Henry reaction of various isatin derived N -Boc ketimines with nitromethane. This catalytic system did not work well with other nitroalkanes under the above optimized reaction conditions. To examine this catalytic behaviour, quantum chemical DFT calculations were performed with the nucleophiles (CH2 NO2 − and CH3 CHNO2 − ) for the conversion of1a to2a using macrocyclicCu-1B complex. The DFT calculated results have shown that the reaction with CH2 NO2 − is more favourable than the corresponding CH3 CHNO2 − . The calculated activation barriers suggest that the reaction with CH2 NO2 − is ∼8.0 kcal/mol energetically favoured than CH3 CHNO2 − . This catalytic protocol was further used to obtain chiral β -diamines (a building block for pharmaceuticals) at gram scale. In order to elucidate the reaction mechanism of asymmetric aza Henry reaction kinetic experiments were performed with different concentrations of the catalystCu-1B, nitromethane and1g as the representative substrate. The reaction of isatin N-Boc ketimine was first order with respect to the concentration of the catalyst and the nitromethane but did not depend on the initial concentration of the substrate. A possible mechanism for the aza Henry reaction was proposed. Graphical abstract: