Divergent synthetic strategy leading to structurally diverse pyrrolidines and piperidines from common gamma-aminoalkyl butenolide and aldehyde precursors.
Condensation between aldehydes and the secondary amino function of 5-(aminoalkyl)furan-2(5H)-ones, obtained by the silyloxyfuran dienolate addition to imine-type derivatives, produces either aminoalkylbenzotriazoles or 1,2,3,4-tetrahydropyridines. The former can be reduced with SmI2 to generate alpha-aminoalkyl radicals that are trapped by the alpha,beta-unsaturated lactone moiety yielding substituted pyrrolidines diastereoselectively, while catalytic hydrogenation of the latter affords isomeric piperidine analogues. Alternatively, SmI2-promoted reduction of tetrahydropyridines in the presence of acid also leads to intermediate alpha-aminoalkyl radicals that participate in inter- or intramolecular olefin addition reactions. Further manipulation of the lactone functionality in various ways gives access to a number of interesting derivatives based upon either a pyrrolidine or a piperidine structural motif. As a result, a high degree of structural diversity is obtained in a few steps starting from a common set of simple materials.
Aurrecoechea
José M
JM
Departamento de Química Organica II, Facultad de Ciencia y Tecnología, Universidad del País Vasco, Apartado 644, 48080 Bilbao, Spain. jm.aurrecoechea@ehu.es
Suero
Rubén
R
de Torres
Esther
E
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry*; D003500:Cyclization; D005609:Free Radicals / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000447:Aldehydes; D005609:Free Radicals; D010880:Piperidines; D011759:Pyrrolidines; C004511:butenolide; D015107:4-Butyrolactone