Abstract
The nitrogen containing spiro-heterocycle is one of the privileged synthetic motif that constitutes various naturally occurring molecules and displays a broad range of pharmaceutical and biological activities. A new methodology was developed for the synthesis of 2,4-diazaspiro[ 5.5] undecane-1,3,5,9-tetraones spiro-heterocyclic derivatives via cascade cyclization of [5+ 1] double Michael addition reaction of N, N-dimethylbarbituric acid with the derivatives of diaryl-divinylketones in the presence of diethylamine at ambient temperature. The developed protocol is highly capable of furnishing diazaspiro[5.5] undecane derivatives 3a-m in excellent yields (up to 98%), from easily accessible symmetric and non-symmetric divinylketones 2a-m, containing aryl and heteroaryl substituents. The diazaspiro-heterocyclic structure was mainly elucidated by NMR and X-ray crystallographic techniques. The single-crystal X-ray studies revealed that, the cyclohexanone unit of spirocycles often prefers a chair conformation rather than twisted conformation. The intermolecular hydrogen bonding and C-Ar-H center dot center dot center dot pi,pi-pi stacking interactions driving forces are mainly responsible for the crystal packing. (C) 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University.