A Facile Entry into Naphthopyran Quinones via an Annelation Reaction of Levoglucosenone. The Total Synthesis of (-)-Hongconin(1)

The annelation reactions of levoglucosenone, prepared by pyrolysis of paper, with 3-cyano-1(3H)-isobenzofuranone and 3-cyano-5-methoxy-1(3H)-isobenzofuranone have been studied. Reductive ring-opening of the annelation products with zinc/copper couple and subsequent chemical transformations provide a facile entry into the naphthopyran quinone ring system. Standard chemical transformations of the annelation product from 3-cyano-5-methoxy-1(3H)-isobenzofuranone and levoglucosenone afforded (1R)-5,9,10-trimethoxy-1-methyl-1H-naphtho[2,3-c]pyran-4(3H)-one. The lithium enolate of this compound undergoes an interesting and potentially useful reaction with oxygen to afford (3R)-4,5,9-trimethoxy-3-methylnaphtho[2,3-c]furan-1(3H)-one. When oxygen is rigorously excluded, methylation of the enolate could be performed in good yield using 10 equiv of methyl iodide in the presence of 10 equiv of DMPU. This chemistry culminated in a total synthesis of (-)-hongconin in six steps from levoglucosenone.