No abstract

Flavones are important classes of flavonoids and have been isolated from a wide variety of plants, fruits, and vegetables. 1 They have attracted considerable interests due to their diverse pharmacological properties on human health, including antioxidant, anti-inflammatory, anticancer, antifungal, and antimicrobial activities. 2 A number of methods for synthesizing flavones have been reported, 3 which can be mainly classified as cyclodehydration of 1-(2-hydroxyphenyl)-3-phenyl-1,3-propanediones, 4 oxidative cyclization of 2 0 -hydroxychalcones, 5 and carbonylative cyclization of o-iodophenols with arylacetylenes in the presence of palladium catalyst. 6 Recently, the cyclization of o-(alkynon-1-yl)phenols has been investigated as a convenient method of flavone synthesis. However, the intramolecular cyclization of o-(alkynon-1-yl)phenols produced not only flavones via 6-endo-digonal cyclization (path a) but also aurones via 5-exo-digonal cyclization (path b) and the ratio of products was highly dependent on the kinds of reagents and solvents (Scheme 1).The reaction of o-(alkynon-1-yl)phenols and K 2 CO 3 (0.2 equiv) in refluxing acetone afforded products of both 6-endo and 5-exo cyclization as the major of 6-endo mode, while 5-exo cyclization became enhanced when ethanol was used as protic media. 7 The use of triflic acid 8 (1 equiv) in 1,2-dichloroethane or 4-(dimethylamino)pyridine 9 (0.1 equiv) in DMF on the cyclization of o-(alkynon-1-yl)phenols predominantly induced 6-endo cyclization to provide flavones. The 1,4-addition of diethylamine 10 (10 equiv) to O-TBS protected alkynones in EtOH or sodium 2-pyridinethiolate 11 (1 equiv) to o-(alkynon-1-yl)phenols in THF afforded the corresponding enaminoketone or β-(2-pyridylthio)phenoxide intermediates, respectively, which underwent intramolecular cyclization to give flavones at reflux temperature. The treatment of oalkynoylphenyl acetates with CH 3 OK (2.5 equiv) using 18-crown-6 (2.5 equiv) in THF provided the corresponding phenoxide intermediates, which underwent cyclization and subsequent leaving of methoxy group to give flavones. 12 However, the use of PBu 3 13 (0.05 equiv) in EtOH or Cs 2 CO 3 14 (3 equiv) in acetone on the cyclization of o-(alkynon-1-yl)phenols induced the 5-exo cyclization with a high regioselectivity to give aurones. The treatment of o-(alkynon-1-yl)phenols with AgNO 3 15 (0.3 equiv) in CH 3 OH or AgOAc 16 (0.03 equiv) in DMF also induced high 5-exo cyclization via dual-coordination process to give aurones. The reaction of o-(alkynon-1-yl)phenols and sodium 2-pyridyloxide (0.1 equiv) in THF provided the corresponding sodium phenoxides, which underwent 5-exo cyclization kinetically to give aurones after protonation by 2-PyOH. 17 As an extension of our studies on the synthesis of flavones, 11,18 we herein report that flavones can be synthesized by regioselective cyclization of o-(alkynon-1-yl)phenols using 0.05 equiv of thallium(III) p-tosylate in CH 3 OH. Thallium(III) p-tosylate has been utilized for the conversion of flavanones to isoflavo...