Cyclizations trifluoromethanesulfonic anhydride

The Frasca method for obtaining 1-arylindazoles also involves a C(3)—C(3a) ring closure (67CJC697). It consists in the cyclization of p-nitrophenylhydrazones of ketones and aldehydes with polyphosphoric acid. The Barone computer-assisted synthetic design program has found several new methods for preparing indazoles (79MI40409). The selected method involves the transformation of jV, jV -diphenylhydrazides (596) into 1-phenylindazoles (597) by means of trifluoromethanesulfonic anhydride. The yields vary from 2% (R = H) to 50% (R = Ph). 

Beccalli et al. reported a new synthesis of staurosporinone (293) from 3-cyano-3-(lH-indol-3-yl)-2-oxo propionic acid ethyl ester (1464) (790). The reaction of 1464 with ethyl chlorocarbonate and triethylamine afforded the compound 1465, which, on treatment with dimethylamine, led to the corresponding hydroxy derivative 1466. The triflate 1467 was prepared from 1466 by reaction with trifluoromethanesulfonic anhydride (Tf20) in the presence of ethyldiisopropylamine. The palladium(O)-catalyzed cross-coupling of the triflate 1467 with the 3-(tributylstannyl)indole 1468 afforded the vinylindole 1469 in 89% yield. Deprotection of both nitrogen atoms with sodium ethoxide in ethanol to 1470, followed by photocyclization in the presence of iodine as the oxidizing agent provided the indolocarbazole 1471. Finally, reductive cyclization of 1471 with sodium borohydride-cobaltous chloride led to staurosporinone (293) in 40% yield (790) (Scheme 5.248). 

Barrett and Kohrt" ° and Kelly and Lang" independently reported the first examples of oxazole triflates (Scheme 6.17). In both cases, the requisite 2-aryl-4(5/7)-oxazolone, 56 or 59, was treated with trifluoromethanesulfonic anhydride (Tf20) to afford 60a or 60b, respectively, which were then coupled successfully with a variety of organostannanes. Kelly and Lang" attempted to extend this methodology to prepare the key oxazole triflates 63 in their approach to sulfomycin I. However, they were unexpectedly thwarted when 61 could not be cyclized to the requisite 4(57/)-oxazolone precursors 62. Schaus and Panek described an unproved procedure to prepare 56 in 90% yield very recently. 

Electrocyclization is the key step in a route to 4//-imidazoles 1187 and imidazoles 1188. Thus, activation of AT-acylamidines 1183 with trifluoromethanesulfonic anhydride and subsequent condensation with amino compounds 1185 produces l-amino-2,4-diazapenta-l,3-dienes 1186. Deprotonation of 1186 by the use of strong organic bases yields the corresponding 4//-imidazoles 1187 or imidazoles 1188 after amine elimination through an anionic 1,5-electrocyclization reaction. For the cyclization to occur, the amino compound 1185 needs to possess electron-withdrawing substituents such as alkoxycarbonyl or fluorenyl groups (Scheme 290) <2004EJO2567>. 

Primary and secondary amides and thioamides react with alkyl chlorofoimates with loss of CO2 or COS, forming iminium chlorides (82 equation 52). In some cases this method is complementary to the Pinner imido ester hydrochloride synthesis. The iminium salt (83 Scheme 6) formed by action of ethyl chloroformate on DMF is labile and decomposes rapidly to ethyl chloride. If the reaction is performed in the presence of NaBp4, the iminium salt (85) is isolable. Aryl chlorofoimates react in the same fashion with DMF or DMA, but in these cases the aryloxymethyleneiminium compounds are fairly stable, so this reaction is an important method for the preparation of compounds of this type. - Succinic acid monoamides, phthalic acid monoamides and related compounds are cyclized to iminium salts (86 equation 53) by treatment with acetic anhydride and HC104. ° With the aid of trifluoromethanesulfonic anhydride lactams and amides can be converted to dication ether salts (87) and (88 Scheme 7).22i.222... 

An improved and convenient preparation of pyrimidines and condensed pyrimidines from ketones and nitriles was reported. In the presence of acetonitrile, the cation generated from methyl ethyl ketone with trifluoromethanesulfonic anhydride is trapped by the nucleophile, whereby a resonance-stabilized nitrilium species is formed. A second molecule of nitrile reacts with nitrilium intermediate, and after elimination of triflic acid, cyclization, and loss of a proton, the pyrimidine product was obtained in a useful yield. The formation of pyrimidines is accompanied by a minimum... 

An alternative approach to benzo[Z ]thiophene derivatives includes treatment of an aryl-substituted ketene dithioacetal monoxide 188 with trifluoromethanesulfonic anhydride [99] (TfjO) in the presence of K2CO3 in toluene at 25 °C, followed by addition of ethanolamine to the reaction mixture, provided benzo[fc]thiophenes, including 3-trifluoromethylbenzo[Z ]thiophene 189, in good yields. The cyclization proceeded through formation of reactive sulfonium electrophile [1(X)]. The synthesis of the starting material 188 was also facile and scalable, starting from aryl ketone 186 and formaldehyde dimethyl dithioacetal S-oxide (FAMSO) [101]. 

The Schiff base derivatives 73 of the 3-hetaryl-substituted 4-amino-3-thiol-l,2,4-triazoles, on treatment with acetic anhydride, undergo cyclization to give the corresponding 3-substituted-5-acetyl-5,6-dihydro-6-phenyl[l,2,4]triazolo[3,4-7][l,3,4]thiadiazoles 76 (Equation 16) <1990IJB135>. Similar treatment of 4-(A-bcnzoylamino)-4,5-dihydro-l-methyl-3-mcthylthio-1 //-[ 1,2,4 triazolc-5-thione 77 leads to the [l,2,4]triazolo[3,4-4][l,3,4]thiadiazolium trifluoromethanesulfonate 78 (Equation 17) <1986LA1540>. 

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