SYNTHETIC APPROACHES TOWARD SPIRO[2,3-DIHYDRO-4H-1-BENZOPYRAN-4,1'-CYCLOHEXAN]-2-ONE DERIVATIVES VIA RADICAL REACTIONS - TOTAL SYNTHESIS OF (+/-)-LYCORAMINE

Syntheses of spiro[2,3-dihydro-4H-1-benzopyran-4,1'-cyclohexan]-2-one derivatives by reaction sequences including a radical reaction and a total synthesis of (+/-)-lycoramine (2) are described. Radical reactions (Bu3SnH,AIBN) of 1-[(1'-cyclohexenylmethyl)oxy]-2-halobenzenes 23b-d in boiling benzene gave the corresponding spiro[2,3-dihydrobenzofuran-3,1'-cyclohexanes] 26a,b in good yields, whereas the reaction of 1-(1'-cyclohexenylethoxy)-2-bromobenzene (25) under similar conditions afforded a mixture of spiro[2,3-dihydro-4H-1-benzopyran-4,1'-cyclohexane] 27 and benzoxepin 28. Furthermore, the radical reaction of ethyl 2-[(2'-bromoaryl)oxy]-1-cyclohexenylacetate 37a produced ethyl 2-spiro[2,3-dihydrobenzofuran-3,1'-cyclohexane]carboxylate 38 in good yield. Compound 38 was converted to spiro[2,3-dihydro-4H-1-benzopyran-4,1'-cyclohexane]-2,4'-dione 40 by treatment With SmI2 and then with 3 N HCl. Spiro[2,3-dihydro-4H-1-benzopyran-4,1'-cyclohexane]-2,4'-dione 40 was transformed to (+/-)-lycoramine (2) in four steps and 43% overall yield.