DNMR study of atropisomeric 1-arylpyrrolidin-2-imines

JIMENA E. DÍAZ; ANDREA MAZZANTI; MICHELE MANCINELLI; LILIANA R. ORELLI

Praga

Simposio; CHIRALITY 2014. 26th International Symposium on Chiral Discrimination, ISCD-26; 2014

Academy of Sciences of the Czech Republic

Atropisomerism is a property of some molecules that exist as enantiomeric forms due to restricted rotation around peculiar single bonds, which behave as chiral axes. In the last years, there was a growing interest for the development of stable non-biaryl atropisomers, due to their potential employment in stereoselective synthesis. Our group has discovered and investigated some new families of atropisomeric heterocycles.1,2 1-Arylpyrrolidin-2-imines 1 are cyclic amidines where the sp2 nitrogen is exocyclic. When the aryl moiety is 2-substitued (Ar*), the two rings adopt a non-coplanar conformation, allowing for the existence of an atropisomeric pair. 1, Ar= 2-F,Cl,Br,OCH3,CH3C6H4; 2, Ar=2-ClC6H4 In this work we present the determination of the enantiomerization barriers of compounds 1 by means of variable temperature NMR and lineshape analysis (DNMR). We discuss the influence of the stereoelectronic nature of the substituents on the magnitude of the enantiomerization barriers. We also determined the barrier for the E/Z equilibrium entailed by the =NH moiety in two derivatives. We additionally report the barrier of compound 2, in which the NH moiety is substituted by an oxygen, in order to address the influence of the exocyclic heteroatom. The conformational ground states and the structures of the transition states were calculated using Density Functional Theory (DFT).