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A new methodology for the use of alkoxides as nucleophiles in (ir-allyl)palladium chemistry has been developed. In this process an allylic alcohol serves as the precursor to the ir-allyl complex and a triethylsilyl (TES) ether as precursor to the alkoxide nucleophile. By using Pd(PPh3)4 in CC14, PPh3Cl+CCl3" is generated transposing the ROH into an oxyphosphonium group, R-0-P+Ph3, and liberating Cl". The Cl deprotects the TES ether, providing the nucleophile in situ. Application of this reaction to the preparation of a variety of furans is discussed. This process was determined to proceed with overall predominant retention of configuration. Mechanistic studies suggest a small energy difference between attack by alkoxide on the allyl ligand of the intermediate complex and attack on the metal, followed by reductive elimination.

In order to investigate new antiulcer agents, spizofurone 1 (AG-629) was fragmented and reassembled to generate 5-phenyl-2,2-dimethyl-3(2H)-furanone (bullatenone, 2). Because of the antiulcer activity of 2,5-phenyl-substituted 2,2-dimethyl-3(2H)-furanones (3-6) were made and shown to have poor activity. Insertion of an ethenyl link between the furanone and phenyl rings gave 5-(2-phenylethenyl)-2,2-dimethyl-3(2H)- furanone (7). This compound had better activity than 2. Compounds 8-41 were synthesized to evaluate the SAR in 5-(2-ethenyl substituted)-3(2H)-furanones. Electron-withdrawing substituents on the aromatic ring (8, 10, 19, and 20) gave 2-3-fold higher activity. Further increases in the activity were found when the phenyl ring was replaced by heterocyclic nuclei. Compounds that contained a thiophene (29), pyridine (24-26), or quinoline ring (32) had the best activity. Replacement of the methyl group on the furanone ring with a phenyl (34) or p-fluorophenyl (40) substituent in the 2-pyridine series gave compounds with activity that ranked with the best obtained in this study. The best compounds from the above SAR studies were evaluated in the ethanol-necrosis model for duration of cytoprotection action. Compounds 19, 24, and 29, which had the best duration of action, were tested with AG-629 in the acidified aspirin and indomethacin-induced lesion models. Only compound 24 had equivalent activity with AG-629 in both models.

Thermolysis of Benzo[c ]fluorenone 13a. A solution of 0.17 mmol of 13a, dissolved in 20 mL of diphenyl ether, was thermolyzed at 250 °C in the dark during 18 h. Preparative TLC on silica gel with benzene-hexane (4:1), after removal of the diphenyl ether as usual, yielded besides 13a, a red product; recrystallization from heptane afforded 0.13 mmol of the benzo[c]fluorenone 16 (77%): mp 193 °C; IR 1690 cm"1 (pc=0); lH NMR (CDClg/ ) 2.53/0.35 (3, s, 5-CH3), 2.72/-0.03 (3, s,, 3.86/0.66 (3, s,