Synthesis using triflates

Oxo-bridged diiodonium triflate [Zefirov s reagent), a useful reagent for the synthesis of triflate esters and iodonium salts, can be prepared by the treatment of lodosobenzene with triflic anhydride [92] or by the reaction of lodobenzene diacetate with tnflic acid [93] (equation 44). 

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). 

Nguyen MP, Arnold JN, Peterson KE, Mohan RS (2004) Environment-friendly organic synthesis using bismuth compounds bismuth triflate catalyzed synthesis of substituted... 

FIGURE 8.1 Continuous flow synthesis using microreactor and affinity separation system. Ac, acetyl Bn, benzyl TfO, triflate Troc, trichloroethoxycarbonyl. 

Palladium-catalyzed phosphination of substituted aryl bromides, using triarylphosphines as the phosphinating agents, has been developed, as illustrated by the synthesis of (57) (Equation (18)).89 This method tolerates various functionalities, e.g., ketone, aldehyde, ester, nitrile, ether, and chloride. Under similar catalytic conditions, various P,/V-ligands, e.g., (58) (Scheme 4), were synthesized using triflate precursors instead.90,91 Arylphosphines can also be prepared by phosphination with triphenylphosphine catalyzed by palladium on charcoal.92... 

Recently, polymer-supported lanthanide catalysts have beem of great interest, and these topics are discussed elsewhere. Use of lanthanide catalysts in solid-phase organic synthesis is now well-recognized [107]. There have also been many transformations other than carbon-carbon bond-forming reactions in organic synthesis using lanthanide triflates as catalysts, and all these will be reviewed in the near future. 

The process was further improved by replacing diphenylethylene with thiophene in the end-capping process [109], The advantage of this modification was related to the quantitative functionahzation of Hving PIB with thiophene, and the possibility of metallation of the thiophene end groups with n-BuLi. This is an important improvement for industrial processes, as lithiation by -BuIi is much more convenient than metallation with a Na/K alloy. Another example of this strategy is the one-pot synthesis of a novel polyoxetane-b-poly(e-caprolactone) by sequential CROP and AROP, using triflate complexes of bulky titanium bispheno-lates [110]. 

The use of triflates for introducing iodide and fluoride into carbohydrates is mentioned in Chapter 7. Glycosyl synthesis using glycosyl sulphonates is described in Chapter 3,... 

As discussed, [ F]FDG is the most widely used radiotracer, consequently this has been the most studied reaction when benchmarking the efficiency of microreactor technology for this appUcation. In this synthesis, maimose triflate (44) is first reacted with the activated fluoride complex to give (45), followed by hydrolysis under acidic or basic conditions to give [ F]fluorodeoxyglucose ([ F]FDG) (46) (Scheme 6.15). 

Carboxylic acids are produced in water. Selection of solvents is crucial and the carbonylation of the enol triflate 480 can be carried out in aqueous DMF, and that of the aryl triflate 481 in aqueous DMSO using dppf as a ligand[328,334]. The carbonylation of the enol triflate 482 to form the a, 0. unsaturated acid 483 using dppf as a ligand in aqueous DMF has been applied in the total synthesis of multifunctionalized glycinueclepin[335]. 

The coupling of the enol triflate 703 with the vinylstannane 704[397] has been applied to the synthesis of glycinoeclepin[576]. The introduction of a (Z)-propenyl group in the / -lactam derivative 705 proceeds by use of tri-2-furylphosphine[577]. However, later a smooth reaction to give the propenyl-iactam in 82% yield was achieved simply by treating with Pd(OAc)2 in NMP or CH2CI2 for 3-5 min without addition of LiCI and the phosphine ligand[578]. 

Lewis acids such as zinc triflate[16] and BF3[17] have been used to effect the reaction of indole with jV-proiected aziridine-2-carboxylate esters. These alkylations by aziridines constitute a potential method for the enantioselective introduction of tryptophan side-chains in a single step. (See Chapter 13 for other methods of synthesis of tryptophans.)... 

Tri.-nethylsilyl triflate (TMSOTf), PhSCH, CF3COOH. These conditions also cleave the following protective groups used in peptide synthesis (MeO)Z-, Bn-, Ts-, CI2C6H3CH2-, BOM (benzyloxymethyl)-, Mts-, MBS-, r-Bu-SR, Ad-SR, but not a BnSR, Acm, or Arg(N02) group. The rate of cleavage is reported to be faster than with TfOH/TFA. 

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... 

Trimethylsilyl trifluoromethanesulfonate (trimethylsilyl triflate) is the most synthetically useful representative of the family of trialkylsilyl perfluoroalkane-sulfonates (for a review, see reference 101) This reagent is commercially available or can be prepared easily by the reaction of chlorotrimethylsilane and triflic acid [101] It has wide application in organic synthesis as an excellent silylating reagent... 

Another triflate ester that recently has found growing application in organic synthesis is commercially available trimethylsilylmethyl trifluoromethanesul fonate. This powerful alkylating reagent can be used for the synthesis of various methylides by an alkylation-desilylation sequence A representative example is the generation and subsequent trapping by 1,3-dipolar cycloaddition of indolium methanides from the corresponding indole derivatives and trimethylsilylmethyl trifluoromethanesulfonate [108] (equation 54)... 

Triflates of titanium and tin are effective catalysts for various condensations of carbonyl compounds [I2I, 122, 123, 124, 125] Claisen and Dieckmann type condensations between ester functions proceed under mild conditions in the presence of dichlorobis(trifluoromethanesulfonyloxy)titaiiiuin(rV) and a tertiary amine (equations 59 and 60) These highly regio- and stereoselective condensations were used successfully m the synthesis of carbohydrates [122]... 

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