Nitrogenous Natural Products Synthesis via N-Acylnitroso Diels-Alder Methodology

N-Acylnitroso compounds bearing an attached conjugated diene system, generated in situ by periodate oxidation of the corresponding hydroxamic acids, are highly reactive with respect to intramolecular cycloaddition to form the corresponding bicyclic 1,2-oxazinolactams. When the reaction is performed in aqueous media with chiral hydroxamic acids, significant enhancement of trans selectivity is observed. A key feature involved in this approach is completely stereocontrolled introduction of an alkyl side chain or aryl group into the pyridoxazine ring by means of the Grignard addition-reduction sequence. Various derivatives of the pyridoxazine nucleus are thus obtained in racemic and chiral forms, which, on reductive cleavage of the nitrogen-oxygen bond, give rise to 4-amino alcohols. The latter can be utilized as building blocks for the development of stereoselective total syntheses of nitrogen-containing natural products including the piperidine, indolizidine, and decahydroquinoline alkaloids.

N-acylnitroso compounds - intramolecular hetero Diels-Alder reaction - bicyclic 1,2-oxazinolactams - alkaloids - enantioselective synthesis