STEREOCHEMICAL EVIDENCE ON THE MECHANISM OF RING CLOSURE OF AMIDOALCOHOLS TO OXAZOLINES PROMOTED BY PPA ESTERS

MARÍA CRUZ MOLLO; LILIANA R. ORELLI

Carlos Paz

Conferencia; 13th Latin American Conference on Physical Organic Chemistry; 2015

Universidad Nacional de Córdoba

2-Oxazolines represent a heterocyclic core of great interest due to its biological properties. In organic chemistry, such compounds can be used as protective groups of carboxylic acids, aminoalcohols and aldehydes and as synthetic intermediates or precursors. Besides, chiral oxazolines and bisoxazolines are widely employed as ligands in asymmetric synthesis. As a consequence, new methods toward their synthesis are constantly developed. Poyphosphoric acid (PPA) ethyl and trimethylsilyl esters (PPE and PPSE, respectively) find application in a variety of organic reactions, acting as mild irreversible dehydrating agents of the Lewis acid type. We have previously demonstrated their efficiency in the microwave-assisted synthesis of various dinitrogen heterocycles. More recently, we have investigated their use in the heterocyclization of amidoalcohols leading to 2-oxazolines and their 6 and 7-membered homologues. In the present work, we explore the scope of the method and focus on the mechanism of the ring closure reaction involved in the microwave-assisted synthesis of 2-oxazolines from amidoalcohols promoted by PPA esters. In particular, we studied the reaction of chiral amidoalcohols bearing a 5-methyl substituent (R2=Me). The stereochemical outcome of the reaction was investigated, allowing us to propose a plausible mechanism for the reaction and to evaluate the role of PPA esters in this synthetically useful transformation.