Double π-Bond Isomerization/Friedel–Crafts Reaction Involving γ-­Amidocronates: Access to γ-Aryl/Heteroaryl GABA Scaffolds and Dihydropyrido[1,2-a]indoles

Abstract

A series of pharmacologically attractive γ-indolyl/furyl/aryl-substituted γ-amino esters/γ-aminoketones were obtained in good to high combined yields by π-bond isomerization of N-protected γ-aminocrotonates/γ-aminocrotonophenones in the presence of triethylamine, followed by tandem Friedel–Crafts alkylation involving several indole/furan/arene derivatives and the resultant N-protected enamines at room temperature by using B(C6F5)3(5 mol-%) as an efficient Lewis acid catalyst. Moreover, the easy synthesis of the important class of 8,9-dihydropyrido[1,2-a]indole scaffolds was realized by this unique procedure. Thus, a simple, convenient, and metal-free-based protocol may provide an alternative powerful synthetic route for heteroarylation/arylation at the γ positions of GABA derivatives in a practical manner. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim