Base-controlled diastereodivergent synthesis of (R)- and (S)-2-substituted-4-alkylidenepiperidines by the Wadsworth-Emmons reaction.
Significant base and reaction time effects have been observed in the Wadsworth-Emmons reaction between a chiral 2-substituted-4-oxopiperidine and phosphonates. In the reactions carried out using a large excess of DBU as the base and prolonged reaction times, the initially formed 2R products epimerized into thermodynamically more stable products through a retro-conjugate/conjugate addition sequence and 2-substituted-4-alkylidenepiperidines of 2S configuration were selectively synthesized. In contrast, when the reaction was carried out using LDA as the base, epimerization did not occur and 2-substituted-4-alkylidenepiperidines of 2R configuration were obtained with excellent yields.
Etayo
Pablo
P
Departamento de Química OrgAnica, Instituto de Ciencia de Materiales de Aragón, Instituto Universitario de CatAlisis Homogénea, Universidad de Zaragoza-CSIC, E-50009 Zaragoza, Spain.
Badorrey
Ramón
R
Díaz-de-Villegas
María D
MD
Galvez
José A
JA
D000466:Alkadienes / Q000138:chemical synthesis*; D008024:Ligands; D008956:Models, Chemical; D063065:Organophosphonates / Q000737:chemistry*; D010880:Piperidines / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013816:Thermodynamics
D000466:Alkadienes; D008024:Ligands; D063065:Organophosphonates; D010880:Piperidines