Novel Bicycloannulation via Tandem Vinylation and Intramolecular Diels-Alder Reaction of Five-Membered Heterocycles: A New Approach to Construction of Psoralen and Azapsoralen

Article abstract of DOI:10.1021/ja00334a044

trans-4-(Phenylsulfinyl)-3-buten-2-one (1) was found to undergo a new versatile addition-elimination reaction with five-membered compounds such as furans, pyrroles, imidazole, pyrazole, and 6-(dimethylamino)fulvene to give an excellent yield of the corresponding trans-4-aryl-3-buten-2-ones (3).The thermal reaction of the propargyl ethers 7a,b prepared from 3a,b gave a single intramolecular Diels-Alder adduct, 8a,b, in 59percent and 38percent yields, respectively.Treatment of 7a,b with t-BuOK in refluxing tert-butyl alcohol afforded another type of Diels-Alder adduct, 10a,b, in almost quantitative yields.This bicycloannulation strategy was applied to a new synthesis of psoralen which is of current interest due to its unique photoreactivity with DNA.The acid-catalyzed reaction of sulfoxide 12, prepared from ethyl acatoacetate in high yield, with furan gave 13 in 78percent yield.The intramolecular Diels-Alder reaction of the neopentyl acetal of 13 in the presence of Pd/C followed by acid hydrolysis afforded the tricyclic ketone 18 in 38percent yield.Baeyer-Villiger oxidation and dehydrogenation of 18 completed the synthesis of psoralen (11).Furthermore, hitherto unknown azapsoralen 20 was also synthesized by this method.