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.
Departamento de Síntesis y Estructura de Biomoléculas, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), Universidad de Zaragoza, CSIC, 50009, Zaragoza, Aragón, Spain.
Veronica
http://orcid.org/0000-0002-5094-2843
V
Juste-Navarro
Servicio de Resonancia Magnética Nuclear, Centro de Química y Materiales de Aragón (CEQMA), Universidad de Zaragoza, CSIC, Campus San Francisco, 50009, Zaragoza, Spain.
Ignacio
http://orcid.org/0000-0001-8355-2289
I
Delso
Departamento de Síntesis y Estructura de Biomoléculas, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), Universidad de Zaragoza, CSIC, 50009, Zaragoza, Aragón, Spain.
Tomás
http://orcid.org/0000-0003-3433-6701
T
Tejero
Departamento de Síntesis y Estructura de Biomoléculas, Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), Universidad de Zaragoza, CSIC, 50009, Zaragoza, Aragón, Spain. pmerino@unizar.es.
Pedro
http://orcid.org/0000-0002-2202-3460
P
Merino
azomethine ylides; density functional calculations; lithium; nitrones; oxazolines