Catalyst free enantioselective amination via SN2 nucleophilic substitution reaction: a computational study. Issue 12 (12th August 2020)

• Record Type: Journal Article
• Authors: Singh, Amritpal; Chayawan, ; Mehta, S. K.; Singh, Kulvinder
• Is Part Of: Molecular simulation. Volume 46:Issue 12(2020)
• Page Start: 942
• Page End: 946
• Publication Date: 2020-08-12
• Subjects: Density functional theory -- amination -- enantioselective -- hydrogen bonding; Molecular dynamics -- Computer simulation -- Periodicals; Statistical mechanics -- Computer simulation -- Periodicals; 539.6
• DOI: 10.1080/08927022.2020.1795167
• Languages: English
• ISSNs: 0892-7022

Abstract

ABSTRACT: Herein, we have developed a new route towards the enantioselective synthesis of chiral amines without any chiralcatalyst through SN 2 nucleophilic substitution reaction of 5-dichloromethyl-4-difluoromethylene-2, 3-dimethyl-3, 4-dihydro-quinazoline [A] with methylamine using Density Functional Theory (DFT) framework. DFT results reveal that the formation of both the enantiomers are exothermic in nature. The activation energy for R- and S-enantiomer comes out to be 52.02 and 37.15 kcal/mol respectively. Also, the bond distance of hydrogen bonding (N1–H-----F–C=C–) in S-enantiomer comes out to be 2.10 Ǻ which is not feasible in R-enantiomer. Thus, the free energy profiles and structural parameters along the reaction coordinates provide enough evidence to conclude that amination will result in the enantioselective formation of S-enantiomer and this stereoselectivity is accredited to intramolecular H bonding (N–H-----F–C = C–) involved in the transition state corresponding to the formation of S-enantiomer. To the very best of our information, this is the first report proposing enantioselectivity in SN 2 reaction without any chiral catalyst/chiral auxiliary through intramolecular hydrogen bonding. GRAPHICAL ABSTRACT: