Diastereoselective, three-component cascade synthesis of tetrahydrofurans and tetrahydropyrans employing the tandem Mukaiyama aldol-lactonization process.
A full account of studies leading to the development of a cascade sequence that generates as many as two C-C bonds, one C-O bond, and three new stereocenters providing substituted tetrahydrofurans (THFs) from simple gamma-ketoaldehydes and thiopyridyl ketene acetals is described. The process involves a tandem Mukaiyama aldol-lactonization (TMAL) and accumulated evidence suggests the intermediacy of a silylated beta-lactone that is intercepted by the pendant ketone. Formation of a cyclic oxocarbenium is followed by reduction with silicon-based nucleophiles leading to a highly diastereoselective synthesis of tetrahydrofurans. This cascade process has now been extended to the synthesis of tetrahydropyrans from simple delta-ketoaldehydes. The stereochemical outcome of the cascade processes described was determined by NOE correlations, coupling constant analysis, and X-ray crystallography of the derived oxygen heterocycles and is in accord with established and recently proposed models for nucleophilic additions to cyclic 5- and 6-membered oxocarbenium ions. The utility of this process was demonstrated by the synthesis of the tetrahydrofuran fragment of colopsinol B.
Mitchell
T Andrew
TA
Department of Chemistry, Texas A&M University, P.O. Box 30012, College Station, Texas 77842-3012, USA.
Zhao
Cunxiang
C
Romo
Daniel
D
D000447:Aldehydes / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003500:Cyclization; D005663:Furans / Q000138:chemical synthesis*; D007659:Ketones / Q000138:chemical synthesis; D007783:Lactones / Q000138:chemical synthesis*; D008958:Models, Molecular; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D011714:Pyrans / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000447:Aldehydes; D005663:Furans; D007659:Ketones; D007783:Lactones; D011714:Pyrans