Cyclizations methanesulfonic acid

In Entry 10, intramolecular acylation is followed by dehydrohalogenation. Entries 11 and 12 illustrate the use of polyphosphate ester. The cyclization in Entry 13 is done in neat methanesulfonic acid. 

Cyclization of the Weinreb amide 356 under reductive conditions using lithium aluminium hydride (LAH) led to formation of the carbinolamine 357 which underwent elimination on treatment with methanesulfonic acid to give 358 in 72% yield as shown in Scheme 27 <2005TL249>. 

This reaction has been studied in mote detail, and a study of the cyclization of thiobenzamide using DMSO as oxidant led to the following conclusions. There must be an oxygen donor oxidant present and it is essential to use a solvent of high polarity such as dimethyl formanide (DMF). An acid catalyst is essential and the counterion is also important HCl and HBr are good catalysts but sulfuric acid, methanesulfonic acid, and trifluoroacetic acid do not give... 

Akermark et al. reported the palladium(II)-mediated intramolecular oxidative cyclization of diphenylamines 567 to carbazoles 568 (355). Many substituents are tolerated in this oxidative cyclization, which represents the best procedure for the cyclization of the diphenylamines to carbazole derivatives. However, stoichiometric amounts of palladium(II) acetate are required for the cyclization of diphenylamines containing electron-releasing or moderately electron-attracting substituents. For the cyclization of diphenylamines containing electron-attracting substituents an over-stoichiometric amount of palladium(II) acetate is required. Moreover, the cyclization is catalyzed by TFA or methanesulfonic acid (355). We demonstrated that this reaction becomes catalytic with palladium through a reoxidation of palladium(O) to palladium(II) using cupric acetate (10,544—547). Since then, several alternative palladium-catalyzed carbazole constructions have been reported (548-556) (Scheme 5.23). 

Cyclizations can also be carried out with an esterified oligomer of phosphoric acid called polyphosphate ester. This material is soluble in chloroform.49 (See entries 11 and 12 in Scheme 11.4.) Another reagent of this type is trimethylsilyl polyphosphate.50 Neat methanesulfonic acid is also an effective reagent for intramolecular Friedel-Crafts acylation.51 (See entry 13 in Scheme 11.4.)... 

Diphenyl ether undergoes cyclization to dibenzofuran in good yield on treatment with 1-2 mol equiv of palladium(II) acetate in boiling solvents such as acetic acid or trifluoroacetic acid or mixtures of acetic acid and methanesulfonic acid (15 The rate of reaction is greater in the more... 

An efficient chemical process for closing a diphenylamine is that using palladium(II) acetate (2 mol for substrates carrying electron-withdrawing groups) in acetic acid-methanesulfonic acid. Carbazole formation has been achieved with alkyl-, halo-, nitro-, and carboxyl-substituted diphenylamines. 1-Chlorocarbazole and carbazol-l-yl carboxylic acid as examples were efficiently prepared. - This is probably the best method now available for cyclizing diphenylamines. 

Secondary and tertiary (3-hydroxy amides can be cyclized to oxazolines in the presence of strong acids such as methanesulfonic acid or p-toluenesulfonic acid. For tertiary (3-hydroxy amides, elimination to the enamide can often be a competing... 

Corey and Ishihara s synthesis of phe-box ligand 29 began with the trifluoro-acetyl derivative of (5)-phenylglycine 26. Treatment of 26 with methylmagnesium iodide, as shown in Figure 9.7, followed by potassium hydroxide in methanol afforded amino alcohol 27 in 88% yield (2 steps).This was then acylated with dimethylmalonyl dichloride 24 and triethylamine followed by cyclization using methanesulfonic acid at reflux to afford phe-box ligand 29 in 78% yield. 

An alternative focus based on known antitumor activity of adriamycin-type systems stimulated the synthesis of the aza-anthraquinones 599 and 600 (Scheme 177) (84CC897). Thus, synergistic chloro-oxazoline directed metalation of 597 with methyllithium followed by treatment with 2,5-dimethoxybenzaldehyde and acid-promoted cyclization provided the lactone 598. Radical bromination and base-induced hydrolysis gave an intermediate keto acid which, upon Friedel-Crafts cyclization with methanesulfonic acid, led to the aza-anthraquinone 599 in modest yield. The azanaphthacene dione 600 was prepared by an analogous series of reactions starting with 597. 

A mixture of methanesulfonic acid and P2Os used either neat or diluted with sulfolane or CH2C12 is a strongly acidic system. It has been used to control the rcgiosclcctivity in cyclization of unsymmetrical ketones. Use of the neat reagent favours reaction into the less substituted branch whereas diluted solutions favour the more substituted branch[3]. 

Commercially available 5-hydroxyethyl-4-methylthiazole has been used in the preparation of the azomethine ylides (588) and (589) (81TL2727). These reacted in good yield with several unsaturated alkenes to provide the adducts (590) which cyclized on silica gel chromatography to (591). The product with X = OEt and Z = C02Et was further transformed into the pyrrole (592) by reaction with methanesulfonic acid in methanol followed by quenching with triethylamine (Scheme 129). 

On another front, the mixture of allylic alcohols 512 and 513 was converted by reaction with methanesulfonic acid anhydride in the presence of triethylamine to a mixture of the corresponding mesylates, which were subjected collectively to methanolysis to afford 514, and none of the allylic ether epimeric at C-3 was isolated. N Debenzylation of 514 followed by a classic Pictet-Spengler cyclization then afforded ( )-buphanisine (361) (208). 

The acidolysis of 3- Wc>-(azidomethyl)bicyclo[3.3.1]non-6-ene with methanesulfonic acid gave 4-azahomoadamant-4-ene 30 via 7t-route cyclization and rearrangement of the intermediate 2-azidoadamantane. Acidolysis of 3-mfo-azidobicyclo[3.3.1]non-6-ene, however, followed by base treatment gave 2-azaadamantan-4-ol (31)137. 

The cyclocondensation of l-alkynyl(phenyl)-Aiodanes with thioureas and thioamides is also a useful method for thiazole synthesis <05AG(E)6896>. For instance, reaction of iodane 36 with thiourea in the presence of triethylamine affords 2-aminophenylthiazole 38. When the same reaction is carried out in the absence of triethylamine, thiazole 38 is not formed instead the isothiouronium mesylate 37 MsOH is isolated in 82% yield. Exposure of this mesylate to an aqueous solution of sodium bicarbonate produces 38 through an intramolecular 5-endo digonal cyclization. Presumably, methanesulfonic acid, generated... 

Cyclization of tetrahydropyranyl ether (245) with BF3-Et20 in trichloroethanol gives (246) in 61% yield. Similar cyclizations can be carried out on acylal derivatives. Acid-catalyzed cyclization of 1-cyclohexeneacetic acid (247) with formaldehyde gives (249) via the presumed intermediacy of (248). If the terminal end of the double bond is more highly substituted, cyclization occurs in an exocyclic mode to give (83). Treatment of (250) with methanesulfonic acid gives (251), which cyclizes to give (252) after loss of a proton (Scheme 36). ... 

A remarkable observation is the cyclization of biscarbamate (194) to y-lactone (195) mediated by methanesulfonic acid (equation 133). No trace of the expected 8-lactone is formed, presumably because of the unfavorable ester geometry in the transition state required for six-membered ring formation. Such problems with 8-lactone formation have been observed also in Diels-Alder chemistry. A nice example related to A-acyliminium chemistry is the thermal hetero Diels-Alder reaction of acylimine precursor (196) to bicyclic -y-lactone (197) in good yield. The corresponding intramolecular cycloaddition of (198) fails. Finally, Lewis acid mediated cyclization of allylsilane (199) is unsuccessful, although lactonization of (200) proceeds very well (equation 135, cf. equation 119). ... 

The acid catalyzed cyclization of 2-acylphenylacetonitriles 94 was investigated using strong acidic conditions. It was found that the use of Amberlyst ion exchange resins, such as A-15 and A-XNlOlO In place of sulfuric or methanesulfonic acid provided 1-substituted 2//-isoquinolin-3-ones 95 (Scheme 42) in improved yields <04JHC979>. 

In another approach, the A((l)-y-hydroxypropyl isomer of (439) was cyclized in methanesulfonic acid <79CPB880>. Compounds (360)-(362) were formed (via the A -l-acylated intermediates) in high yields, as the only products in the reactions between the appropriate stereoisomeric quin-azolinethiones and acetylenedicarboxylate <89MRC959>. 

Synthetic methods for preparation of 1,2,4,5-tetroxanes have been reviewed recently <2001COR601, 2002RMC113>. The most general method involves acid-catalyzed addition of hydrogen peroxide to carbonyl compounds and subsequent cyclization of the hydroperoxide intermediates. The direct synthesis is carried out normally in the presence of either sulfuric, perchloric, or methanesulfonic acids and affords symmetrically substituted tetroxanes (Equation 26). In many cases, for example, where the carbonyl compound is unsubstituted in the a-position, tetroxanes are contaminated with hexaoxonanes and open-chain hydroperoxides. Selective removal of the more reactive hydroperoxides can be achieved with dimethyl sulfide or potassium iodide. Recrystallization usually removes residual hexaoxonanes but, failing that, heating the mixture with perchloric acid in acetic acid can convert hexaoxonanes to tetroxanes or convert the thermodynamically less stable hexaoxonanes to more water-soluble lactones, which may facilitate the purification process <2002RMC113>. 

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