Enantioselective synthesis of 3,4-dihydro-1,2-oxazepin-5(2H)-ones and 2,3-dihydropyridin-4(1H)-ones from ?-substituted ?-hydroxyaminoaldehydes.

ABSTRACT: The synthesis of 3,4-dihydro-1,2-oxazepin-5(2H)-ones and 2,3-dihydropyridin-4(1H)-ones from ?-substituted ?-hydroxyaminoaldehydes is reported. The ?-hydroxyaminoaldehydes were prepared by enantioselective organocatalytic 1,4-addition of N-tert-butyl (tert-butyldimethylsilyl)oxycarbamate to ?,?-unsaturated aldehydes (MacMillan protocol). Alkyne addition to the aldehydes followed by alcohol oxidation furnished N-Boc O-TBS-protected ?-aminoynones. Removal of the TBS protecting group initiated a 7-endo-dig cyclization to yield previously unknown 3,4-dihydro-1,2-oxazepin-5(2H)-ones. Reductive cleavage of the N-O bond of the oxazepinones and Boc-deprotection provided 2-substituted 2,3-dihydropyridin-4(1H)-ones via 6-endo-trig cyclization. 2,3-Dihydropyridin-4(1H)-ones are versatile intermediates that have been used for the synthesis of many alkaloids. The new protocol allows the synthesis of 3-dihydropyridin-4(1H)-ones carrying an array of substituents at C2 that cannot be prepared from commercial ?-amino acids or by one-carbon homologation of proteinogenic amino acids. The use of readily available ?-hydroxylaminoaldehydes expands the utility of our previously reported method to prepare 2,3-dihydropyridin-4(1H)-ones from ?-amino acids as the source of diversity and chirality. A broad substrate scope is possible because ?-aminoaldehydes can be prepared from ?,?-unsaturated aldehydes by an enantioselective organocatalytic process.

SUBMITTER: Ranade AR 

PROVIDER: S-EPMC3985460 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature