Synthesis of Medium-Sized Heterocycles: Bridged Structures

AGUSTINA LA VENIA; PILAR VENTOSA-ANDRES; VIKTOR KRCHNAK

Estambul

Congreso; 5th EuCheMS Chemistry Congress; 2014

Medium-sized heterocycles are important key intermediates in the synthesis of complex molecules, as well as core structures in natural and pharmaceutical compounds. In particular, seven- and eight- membered heterocyclic systems bearing oxygen or nitrogen atoms are constituents of a large number of medicinal interesting compounds. Therefore the synthesis of this class of heterocyles remains a challenging task for organic chemists. Herein, we present an efficient strategy based on the tandem N-acyliminium ion formation followed by nucleophilic addition, which yields diverse 7- and 8-membered heterocyclic rings from easily accessible acyclic precursors. The key step of the sequence, in which the aldehyde is unmasked under acidic conditions, consists in a series of reactions that exhibit two possible mechanisms controlled by the competition among the different internal nucleophiles. The main route enables the formation of complex bridged bi-, tri- and tetracyclic molecular scaffolds with full stereocontrol of the new chiral carbon. The competing path led to unstable cyclic hemiacetals.