Subject triflate

Tnflrc anhydride is a useful reagent for the preparation of covalent triflate esters from alcohols, ketones, and other organic substrates [66] In many cases, very reactive triflates can be generated m situ and subjected to subsequent transformation without isolation [94, 95, 96, 97] Typical examples are cyclization of amides into dihydroisoqumolines (equation 45) and synthesis of Al-hydroxy-a-amino acid denvatives (equation 46) via the intermediate covalent triflates... 

To investigate the feasibility of employing 3-oxidopyridinium betaines as stabilized 1,3-dipoles in an intramolecular dipolar cycloaddition to construct the hetisine alkaloid core (Scheme 1.8, 77 78), a series of model cycloaddition substrates were prepared. In the first (Scheme 1.9a), an ene-nitrile substrate (i.e., 83) was selected as an activated dipolarophile functionality. Nitrile 66 was subjected to reduction with DIBAL-H, affording aldehyde 79 in 79 % yield. This was followed by reductive amination of aldehyde x with furfurylamine (80) to afford the furan amine 81 in 80 % yield. The ene-nitrile was then readily accessed via palladium-catalyzed cyanation of the enol triflate with KCN, 18-crown-6, and Pd(PPh3)4 in refluxing benzene to provide ene-nitrile 82 in 75 % yield. Finally, bromine-mediated aza-Achmatowicz reaction [44] of 82 then delivered oxidopyridinium betaine 83 in 65 % yield. 

It was envisioned that hydrindanone 83 and cyclopentene 85 could be used as intermediates in the synthesis of e f-retigeranic acid A (1) and e f-retigeranic acid B (2), respectively. To prepare the building block 90, cyclopentene 85 was reduced with diimide (93 %) in order to prevent isomerization and subsequently deprotected with PPTS to yield hydrindanone 90 (quant.), which could provide access to <77/-retigeranic acid B (2) (Scheme 10.7). Hydrindanone 83 was reduced via an enol triflate and then subjected to Pd-catalyzed reduction to provide cyclopentene 91 (87 % from 83). Upon hydrogenation of 91 with Pd/C and cleavage of the acetal with iodine, protected hydrindanone 92 (95 % from 91) was obtained. The deprotection of 92 provided ent-60, whose enantiomer was used in previous syntheses of retigeranic acid A (1) by Corey [14] and Hudlicky [46, 47]. 

The vinyl triflate of Komfeld s ketone has been subjected to Heck reactions with methyl acrylate, methyl methacrylate, and methyl 3-(Af-rerf-butoxycarbonyl-lV-methyl)amino-2-methylenepropionate leading to a formal synthesis of lysergic acid [259]. A similar Heck reaction between l-(phenylsulfonyl)indol-5-yl triflate and dehydroalanine methyl ester was described by this research group [260]. Chloropyrazines undergo Heck couplings with both indole and 1-tosylindole, and these reactions are discussed in the pyrazine Chapter [261], Rajeswaran and Srinivasan described an interesting arylation of bromomethyl indole 229 with arenes [262]. Subsequent desulfurization and hydrolysis furnishes 2-arylmethylindoles 230. Bis-indole 231 was also prepared in this study. 

The original observation of Johnson that alkaline hydrolysis of alkoxysulfonium salts takes place with inversion of configuration at sulfur was utilized recently (110) to invert the configuration of sulflnamides. As was already mentioned, (+)-(5)-p-toluenesulflnyl-pyrrolidine 120 was treated with methyl triflate to give the corresponding methoxypyrrolidino-p-tolylsulfonium triflate 119. The crude salt 119 was then subjected to mild alkaline hydrolysis and gave the enantiomeric sulflnamide (-)-reaction sequence takes place with at least 91% inversion. 

These compounds were to be subjected to conventional triflation by triflic anhydride, followed by treatment with potassium nitrite in DMF. It was expected that in all cases good inversion yields would be obtained with neighboring ester groups, whereas the inversion would be inefficient with benzyl groups. 

Initially, glycoside derivatives carrying a triflate group in the 3-position, were subjected to the test. In order to compare the effects of different ester groups, two types of ester-protected galactopyranosides (8,12) were synthesized. 

The Z-alkene ( ) was subjected to the same sequence (Scheme 4). The triflate ( ) was easily obtained, but in this case reaction with azide ion gave directly the diazoester (22). Molecular models show that the triazoline corresponding to (19) has severe steric interactions and is more accessible to deprotonation (cf. ref. 23). 

Fagnou et al. reported the synthesis of mukonine (11) starting from methyl vanillate (644). This synthesis uses both a palladium(0)-catalyzed intermolecular direct arylation and an intramolecular cyclization reaction. Triflation of methyl vanillate (644) afforded the aryl triflate 645. Using a Buchwald-Flartwig amination protocol, the latter was subjected to direct arylation with 2-chloroaniline (646) to furnish the corresponding diarylamine 647. Finally, intramolecular cyclization of 647 afforded mukonine (11). To date, this is the best synthesis (three steps, 75% overall yield) available for mukonine based on commercially available methyl vanillate (644) (582) (Scheme 5.45). 

Separation selectivify is one of the most important characteristics of any chromatographic sfationary phase. The functionality of the cation and anion and their unique combinations result in ILs with not only tunable physicochemical properties (i.e., viscosity, thermal stability, and surface tension), but also unique separation selectivities. Although the selectivity for different analytes is dominated by the solvation interactions imparted by the cation and anion, all ILs exhibit an apparent and xmique dual-nature selectivity that is uncharacteristic of other popular nonionic stationary phases. Dual-nature selectivity provides the stationary phases the ability to separate nonpolar molecules like a nonpolar stationary phase but yet separate polar molecules like a polar stationary phase [7,8]. Typically, GC stationary phases are classified in terms of their polarity (see Section 4.2.2) and the polarity of the employed stationary phase should closely match that of the analytes being separated. ILs possess a multitude of different but simultaneous solvation interactions that give rise to unique interactions with solute molecules. This is illustrated by Figure 4.2 in which a mixture of polar and nonpolar analytes are subjected to separation on a 1-benzyl-3-methylimidazolium triflate ([BeQlm][TfO] IL 6 in Table 4.1) column [21]. 

Chlorobenzenes activated by coordination of Cr(CO)3 react with terminal alkynes[253]. The 1-bromo-l,2-alkadiene 346 reacts with a terminal alkyne to afford the alka-l,2-dien-4-yne 347(254]. Enol triflates are used for the coupling with terminal alkynes. Formation of 348 in the syntheses of ginkgolide[255] and of vitamin D are examples[256]. Aryl and alkenyl fluorides are inert. Only bromide or iodide is attacked when the fluoroiodoalkene 349 or fluoroiodoar-ene is subjected to the Pd-catalyzed coupling with alkynes[257-259]. 

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