Intramolecular 1,4-Dipolar Cycloaddition: A New Approach to the Assembly of Ring-Fused Heterocycles

Article abstract of DOI:10.1021/jo00296a060

A new approach to ring-fused heterocycle construction involves facile intramolecular 1,4-dipolar cycloadditions with anhydro-4-hydroxy-6-oxo-1,3-thiazinium and -oxazinium hydroxides containing the dipolarophilic side chain (alkynes and alkenes) at the 2-position of the thiazinium and oxazinium nucleus and leads to benzopyrano<4,3-b>pyridin-2(1H)-ones.The anhydro-4-hydroxy-6-oxo-1,3-oxazinium hydroxides were not isolated, being generated in situ from the appropriately substituted benzamides and substituted malonyl dichlorides.The oxazinium cycloadditions were characterized by their "one-pot" nature, the extreme ease with which they occurred, the high yields of pure products obtained, and their versatility.In both series alkenic side chains led to endo cycloadducts; methyl substitution on the alkene resulted in exo cycloadducts.Heating the thiazinium cycloadducts at 200 deg C resulted in the loss of COS and rearrangement of the intermediate ylidic species to 3,4-dihydrobenzopyrano<4,3-b>pyridin-2(1H)-ones via a 1,5-H shift.Similarly, the oxazinium cycloadducts lost CO2 at 80-200 deg C, giving the pyridin-2(1H)-ones in excellent yields.With alkynic side chains the cycloadducts were not isolated.Cycloreversion occurred under these reaction conditions, giving benzopyrano<4,3-b>pyridin-2(1H)-ones.