Cyclizations trifluoromethanesulfonate

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). 

The reaction of crotonaldehyde and methyl vinyl ketone with thiophenol in the presence of anhydrous hydrogen chloride effects conjugate addition of thiophenol as well as acetal formation. The resulting j3-phenylthio thioacetals are converted to 1-phenylthio-and 2-phenylthio-1,3-butadiene, respectively, upon reaction with 2 equivalents of copper(I) trifluoromethanesulfonate (Table I). The copper(I)-induced heterolysis of carbon-sulfur bonds has also been used to effect pinacol-type rearrangements of bis(phenyl-thio)methyl carbinols. Thus the addition of bis(phenyl-thio)methyllithium to ketones and aldehydes followed by copper(I)-induced rearrangement results in a one-carbon ring expansion or chain-insertion transformation which gives a-phenylthio ketones. Monothioketals of 1,4-diketones are cyclized to 2,5-disubstituted furans by the action of copper(I) trifluoromethanesulfonate. ... 

Frejd and co-workers utilized a different tactic for aniline cyclization by first employing a Heck-Jeffery protocol under solvent-free conditions to prepare o-amino dehydrophenylalanine derivatives from o-aminoaryl iodides with the former undergoing a spontaneous la cyclization-elimination sequence to afford 2-methoxycarbonyl indoles <06S1183>. Dimethyl(methylthio)sulfonium trifluoromethanesulfonate (DMTST) was used by the Okuma group to promote the cyclization of o-vinyl-A-p-toluenesulfonylanilide to N-tosylindole <06CL1122>. 

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>. 

In addition to the example depicted in Scheme 20.40 and examples involving a prototropic rearrangement [61], the use of trimethylsilyl trifluoromethanesulfonate to induce the transformation of 212 afforded 213 bearing a keto substituent at the allenic terminus (Scheme 20.44) [81]. Thermolysis of 213 promoted the Myers-Saito cyclization leading to 216. 

Thus, the best compromises for Boc and Fmoc chemistries seem to be cyclohexyl and 2,4-dimethylpent-3-yl (Dmpn), which is of intermediate stability, and the removal of which by trifluoromethanesulfonic acid with the aid of thioanisole (see Section 6.22) leads to minimal imide formation (see Section 6.13). Points to note are that acidolysis of esters by hydrogen fluoride can lead to fission at the oxy-car-bonyl bond instead of the alkyl-oxy bond, thus generating acylium ions that can react with nucleophiles (see Sections 6.16 and 6.22), and that benzyl esters may undergo transesterification if left in methanol. The side reactions of cyclization (see Section 6.16) and acylation of anisole (see Section 6.22) caused by acylium ion formation do not occur at the side chain of aspartic acid.47-51... 

Cyclization of p-hydroxybenzylacetone derivatives 72 proceeds when treated with tetra-butylammonium perrhenate and trifluoromethanesulfonic acid in refluxing CICH2CH2CI, affording azaspirodienones 73 in moderate to good yields (equation 31). The azaspiro-dienones are easily transformed into quinolines via dienone-phenol rearrangement ". ... 

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). 

When the olefinic precursor to 866 was treated briefly with trifluoromethanesulfonic acid in dichloromethane solution, cyclization occurs with installation of the final dodecahedrane framework bond. The predominant product proved to be 557 in which methyl group migration has also taken pla( °l The symmetry of this first dodecahedrane was apparent from its spectral properties and nicely detailed... 

Various alkenes react with diphenyl diselenide/(NH4)2S208, in an aqueous acetonitrile as a solvent in the presence of trifluoromethanesulfonic acid to afford the amidoseleny-lation products. It has been observed that some unsaturated nitriles in dioxane undergo intramolecular cyclization reaction to give the corresponding phenylselenolactones. 

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. 

Dibenzothienobisbenzothiophene has been synthesized by the intramolecular cyclization of aromatic methyl sulfoxides under acid conditions followed by demethylation <1999JMC2095>. Thus, treatment of the corresponding sulfoxide with trifluoromethanesulfonic acid gives the cyclized product which is demethylated in refluxing pyridine (Equation 73). 

Reductive cyclization of o-nitrophenylacetic acids is a very general method of oxindole synthesis (see Section 3.06.2.1.1 for the application of this method to indoles in general). The main problem is efficient construction of the desired phenylacetic acid. One method involves base-catalyzed condensation of substituted nitrotoluenes with diethyl oxalate followed by oxidation of the 3-arylpyruvate (equation 200) (63CB253). Nucleophilic substitution of o-nitrophenyl trifluoromethanesulfonate esters, which are readily prepared from phenols, by dimethyl malonate provides another route (equation 201) (79TL2857). 

Cyclizations of urea derivatives of allylamines with selenium reagents have been examined recently (equation 62 and Table 18).98 Cyclization of the allylic ureas produces franj-2-oxazoline derivatives with high stereoselectivity when the double bond is internal (Table 18, entry 2). Although O-methylisourea derivatives can be cyclized to dihydroimidazoles [see Section 1.9.3.2.2(ii)], cyclization with phenylsel-enenyl trifluoromethanesulfonate and trifluoromethanesulfonic acid produces 5,6-dihydro-1,3-oxazines (6-endo products), even when the double bond is monosubstituted (entry 3). 

The CpW(CO)3 complexes 23 and 24 (obtained from CpW(CO)3Na and propargyl halides) undergo cyclization in the presence of trifluoromethanesulfonic acid (Scheme 9), followed by removal of the metal with trifluoroacetic acid to yield corresponding mono- and bicyclic lactones <1995JA2933>. 

The optically pure bis-naphthalene ortho-methoxy amide 117 cyclized to the l,4-diazepin-5-one 118 in 86% yield and with >95% ee upon refluxing in ethylenediamine for 5 h to provide the first axially chiral 1,4-diazepine derivative (Scheme 64) <2000SL1616>. This example of a type g ring closure in which the leaving group is MeOH, proceeded in lower yield with an ot/ o-hydroxy substituent, with product distribution largely redirected toward an imidazolidine derivative in which the ethylenediamine reacted solely with the ester. In the structurally simpler salicylic acid ester series, activation of the phenol as the trifluoromethanesulfonate facilitated the SnAr reaction <1995TL7595>. 

The condensation of the diamide 371 with the corresponding aldehydes 372 and 373 afforded 374 and 375, respectively, which upon treatment with anhydrous trifluoromethanesulfonic acid in MeCN gave the cyclized products 376 and 377, as a single diastereoisomer (Scheme 79). The action of m-chloropcroxybenzoic acid, followed by the treatment of the monosulfoxide with perchloric acid, resulted in the 1,2,5-dithiazepines 378 and 379 <2000AGE3866>. 

N-Tfa- and iV-Fmoc-a-amino ketones have been synthesized56 by reaction of some N -heterocycles or benzene with chiral AM Tfa- and Fmoc-a-aminoacyl)benzotriazoles [e.g. (49)] in the presence of aluminium trichloride. Full preservation of chirality was reported. Aromatic side-chains in some of the (a-amineacyl)benzotriazole compounds gave a competitive intramolecular cyclization, again with retention of chirality [e.g. (49) to (50)]. A full report57 on the intramolecular acylation of aromatics with Meldrum s acid derivatives catalysed by metal trifluoromethanesulfonates under mild reaction conditions has appeared [e.g. (51) to (52)]. The method tolerates many functional groups and was extended to the synthesis of 1-tetralones, 1-benzosuberones and donepezil (53). 

Phenanthren-9-ylmethyl)phenyl trifluoromethanesulfonate 164 undergoes a palladium-catalyzed cyclization via S-0 bond cleavage to afford 14/f-dibenzo[ ,f]xanthene in moderate yield (Equation 76) <2002T5927>. 

Cyclization of 2,2 -(naphthalene-l,5-diylbis(oxy))dibenzonitrile to form the dixanthone-iminium triflate 801 occurs upon treatment with trifluoromethanesulfonic acid in good yield. Vigorous conditions are required for the hydrolysis of the dixanthone-iminium triflate 801 and the corresponding xantheno[4,3-c]xanthene-8,16-dione 802 is accessed in modest yield (Scheme 223) <20010L2337>. This approach can also be used to synthesize polymeric dixanthones in moderate yield <20010L2337>. 

Cyclization of the sulfides 547 under Friedel-Crafts conditions affords the 4-oxo-l //-2-bcnzothiopyran-l -carboxy-lates (Scheme 229) <1996JOM(507)215, 1999JME751> and treatment of l,l-bis(benzylthio)-2-nitroethene with trifluoromethanesulfonic acid generates a dication which affords the isothiochroman-4-one oxime 548 upon quenching with MeOH (Scheme 230) <2001EJ01525>. 

A new synthetic approach to polycyclic aromatic compounds has been developed based on double Suzuki coupling of polycyclic aromatic hydrocarbon bis(boronic acid) derivatives with o-bromoaryl aldehydes to furnish aryl dialdehydes. These are then converted to larger polycyclic aromatic ring systems by either (a) conversion to diolefins by Wittig reaction followed by photocyclization, or (b) reductive cyclization with trifluoromethanesulfonic acid and 1,3-propanediol (Eq. (12)) [30]. 

N,N-bis-trimethylsilyl enamines (e.g. 269) obtained by sequential addition of methyl-lithium and acyl chlorides to acetyltrimethylsilane cyanohydrin 267, cyclize under thermolysis or by trimethylsilyl trifluoromethanesulfonate treatment to give substituted oxazoles (e.g. 270) (equation 57)140. 

PPA/phosphorus pentoxide (P2OS) cyclization of indole 414 provides azepino[3,4-7]indole-l,5-dione 415 in 86% yield as a precursor for azepino[3,4-7]indol-5-yl trifluoromethanesulfonate, the key intermediate in design of 5-substituted azepino[3,4-3]indol-l-ones (Equation 99) <2000T4491>. 

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