Azomethine ylides from nitrones: Using catalytic nBuLi for the totally stereoselective synthesis of trans-2-alkyl-3-oxazolines

The cycloaddition of azomethine ylide N-oxides (nitrone ylides) with aldehydes provides 3-oxazolines in a completely stereoselective manner in the presence of a catalytic amount of n-butyllithium. The process involves an initial nucleophilic attack on the aldehyde, followed by intramolecular oxygen addition to the nitrone moiety and lithium-assisted elimination of water, regenerating the catalytic species. Various Li-based catalytic systems are possible and the in situ generated water is required for continuing the catalytic cycle. The best results are observed with 20 mol % of n-butyllithium, whereas the use of stoichiometric amounts inhibit the rate of catalysis. Experimental, spectroscopic, and computational mechanistic studies have provided evidence of lithium-ion catalysis and rationalized several competing catalytic pathways.This work was supported by the Spanish Ministerio de Economía y Competitividad (MINECO) (project number CTQ2013-44367-C2-1-P), the Fondos Europeos para el Desarrollo Regional (FEDER), and the Gobierno de Aragón (Zaragoza, Spain, Biorganic Chemistry Group ,E-10). V. J.-N. thanks MINECO for a pre-doctoral grant (FPI program).Peer Reviewe