Aryl trifiate

Ishiyama, T., Itoh, Y., Kitano, T., Miyaura, N. Synthesis of arylboronates via the palladium(0)-catalyzed cross-coupling reaction of tetra(alkoxo)diborons with aryl trifiates. Tetrahedron Lett. 1997, 38, 3447-3450. 

Aryl trifiates, which are readily prepared by use of microwaves [113] from the corresponding aryl alcohol using triflic anhydride or triflic imide, are important halide alternatives but are, occasionally, poorly reactive. Nevertheless, Zhang and Neumeyer have reported palladium-catalyzed activation of trifiates in nitrile couplings for preparation of different K-opioid receptor ligands [109]. As shown in Scheme 15.54, a reaction time of 15 min at 200 °C, in sealed reaction vessels, was sufficient for complete displacement, generating yields between 86 and 92%. 

Scheme 1S.S4. Smooth cyanation using aryl trifiates and palladium catalys...

Gardnerine (28), one of the major indole alkaloids of Gardneria nutans 21), was converted into koumidine (1) (22). The crucial steps in this transformation are deoxygenation from the indole ring by Pd°-assisted reduction of the aryl trifiate derivative (31) and inverting the configuration of the ethylidene side chain in 32 by Pd° catalyst (Scheme 4). 

A solution of the o-(trimethylsilyl)aryl trifiate (1 mmol) in dry acetonitrile (2 mL) is added to a suspension of finely powdered anhydrous CsF (2 mmol) and Pd(PPh3)4 (0.1 mmol) in the same solvent (10 mL). After stirring for 12 h at room temperature under argon, the solvent is evaporated and the residue purified by column chromatography. 

For the palladium-catalyzed cyclotrimerization of arynes, a mechanism similar to the accepted mechanism for [2+2+2] cycloaddition of alkynes may be proposed (Scheme 15). Though it has not been studied in depth, some experimental results support it. Firstly, aryne-forming conditions are necessary for the reaction to proceed (see Table 1, entry 8) no reaction of trifiate 55 takes place at room temperature in the presence of the catalyst if fluoride is absent, which rules out a mechanism initiated by the oxidative addition of the aryl trifiate to palladium. Data obtained in the closely related cocycloadditions of benzyne with alkynes, discussed below, hkewise point to benzyne as the reactive species. Secondly, the benzyne-palladium complex 67 is a plausible initial intermediate because the ability of group 10 metals to coordinate benzyne is well known (see Sect. 1.2.2), and although benzyne complexes of palladium have eluded isolation (apparently because of their instability) [7,26], they may well be able to exist as transient intermediates in a catalytic cycle such as that shown in Scheme 15. Thirdly, it is known that benzyne complex 34 can form metallacy-cles similar to 68, albeit with dcpe as hgand instead of PPhj [26]. 

Another Mizoroki-Heck mechanistic study using ESI-MS was undertaken by Nilsson et al. [28]. In this case, the specific reaction is the microwave-assisted arylation of w-butyl vinyl ether (25), an electron-rich olefin, with aryl triflates in the presence of different palladium sources and with the addition of chelating ligands. Using aryl trifiates as electrophilic partners also generates cationic intermediates, which may be more easily detected by ESI-MS. Scheme 7.12 shows the reactions studied by ESI-MS in this methodological work. 

Odell, L, Savmarker, S. and Larhed, M. Facile aminocarbonylations of aryl trifiates in perparation. 

The transformation that has come to be known as the Heck reaction is broadly defined as the palladium(O)-mediated coupling of an aryl or vinyl halide or triflate with an alkene. The basic mechanism for the Heck reaction of aryl halides or trifiates (as outlined in more detail in the Key Chemistry), involves initial oxidative addition of the chiral palladium(O) catalyst to afford a a-arylpalladium(II) complex. Coordination of an alkene and subsequent carbon-carbon bond formation by syn insertion provide a a-alkylpalladium(II) intermediate, which readily undergoes P-hydride elimination to release the alkene product. Finally, the hydridopalladium(II) complex has to be converted into the active palladium(O) catalyst to complete the catalytic cycle. 

Murata, M., Oyama, T., Watanabe, S., Masuda, Y. Palladium-Catalyzed Borylation of Aryl Halides or Trifiates with Dialkoxyborane A Novel and Facile Synthetic Route to Arylboronates. J. Org. Chem. 2000, 65,164-168. 

It was also discovered that aryl and vinyl iodides, bromides, and trifiates participated efficientiy in cross-coupiing reactions with organostannanes when catalyzed by palladium-on-carbon in the presence of Cu(l) as cocatalyst.f... 

Overman and co-workers [75] prepared alkenyltins via a vinyl triflate/ditin coupling. Mitchell and Kwetkat developed a simple route to acyltrimethylstannanes [187], whereas Hitchcock et al. [ 188] carried out a three-component tandem coupling reaction by reacting a 2-pyridyl trifiate, aryl or heteroaryl bromides, and hexamethylditin with Pd(PPh3)4 in the presence of LiCl to give azabiaryls (Scheme 4-48). 

The original procedure involved the coupling of aryl bromides with secondary amines. However, since then the scope has been expanded to include substrates such as aryl iodides, chlorides, fluorides, trifiates, tosylates, nonafiates, iodonium salts, and even boronic acids. While the reaction has not been extensively utilized with vinyl or alkynyl substrates, it can be performed with various heteroaryl halides. Similarly, numerous types of nitrogen-containing coupling partners, including primary amines, imines, various azoles, lactams, and simple amides, can now be used in this reaction. 

The C-4 acids (183 and 184) have also been subjected to borane reduction conditions to afford alcohol 195 in 23-50% yield or 64% yield as the C-8 epimeric mixture (195 and 196, Scheme 29) [34, 49, 64]. The C-8 alcohol epimers 195 and 196 have been treated separately as a common intermediate for a number of C-4 derivatives including esters, ethers, and amines [34,49, 64]. Alcohols 195 and 196 was subjected to DCC, DMAP, and desired acid chloride or carboxylic acid in CH2CI2 affording ester analogs in 50-92% yield [64]. Esters prepared include alkyl, aryl, and fluorenylmethyloxycarbonyl (Fmoc) protected amino acid derivatives (197 and 198) [64]. Ethers were prepared with various alkyl halides and Ag20 in CH3CN at 40 °C. Alkyl, aUyl, and benzyl ethers were prepared in 45-80% yield (199 and 200) [34,64]. Alcohols 195 and 196 were then activated to the trifiates and displaced by a variety of amines by treatment with trifiuoromethanesulfonic anhydride and desired amine in 22% - quantitative yield over two steps (201 and 202)... 

Aryl chlorides typically do not react under these conditions. However, Miyaura has been able to extend the scope of this reaction to include aryl chlorides by changing the catalyst system to Pd(dba)2 and PCys and replacing pinacolborane with bis(pinacolato)diboron. Vinyl iodides and trifiates undergo borylation with pinacolborane under similar conditions in the presence of triphenylarsine (AsPEb) (eq 17). Benzylic halides react with pinacolborane in the presence of PdCl2, PPhs, and N,N-diisopropylethyl amine (eq 18). Borylation of allylic halides in the presence of Pt(dba)2, AsPhs, and EtsN leads to highly regio-and stereoselective allylboronates (eq 19). 

Fluoroalkyl(aryl)iodonium salts are the most stable and practically important class of alkyl(aryl)iodonium derivatives. The application of such salts as electrophilic fiuoroalkylating reagents was reviewed in 1996 by Umemoto [1017]. Perfluoroalkyl(phenyl)iodonium trifiates (FITS reagents) 764 are efficient perfluoroalky-lating reagents toward various nucleophiUe substrates, sueh as arenes, carbanions, alkynes, alkenes, carbonyl compounds, amines, phosphines and sulfides [1017]. Scheme 3.300 shows several representative examples of electrophilic perfluoroalkylations using FITS reagents. 

Reactivity cximparison Arylation using 1-naphthyi trifiate... 

The coupling of aryl halides and trifiates can be made catalytic in nickel by using zinc as a reductant for in situ regeneration of the active Ni(0) species. 

Cine substitution is encountered occasionally as a result of a slow transmetallation step when sterically encumbered stannanes are used. Flohr [8] carried out studies designed to find a system suitable for the Stille coupling between sterically congested vinyltins and aryl iodides or trifiates he found that under certain conditions the iodides gave ipso products, while the trifiates under somewhat different conditions afforded cine substitution (Scheme 6.3). He also found that the addition of copper iodide was essential for successful coupling of aryl iodides. Mechanistic explanations of this abnormal cross-coupling mode (cine product)... 

Two specific reactions were studied the arylation of n-butyl vinyl ether (25) with two different trifiates, 1-naphthyl triflate (26), and 4-cyanophenyl trifiate (27). The four catalytic systems studied were based on palladacycles 30 and 31, pincer complex 32, Pd(OAc)2 and polyurea encapsulated Pd EnCat30. The authors used dppp (l,3-bis(diphenylphosphino)propane) (33) and (2S,4S)-(-)-2,4-bis(diphenylpho-... 

Kita and coworkers developed an efficient synthesis of aiyl(phenyl)iodonium tosylates from HTIB and arenes in TFE at room temperature [29, 30]. This type of iodonium salt is chemoselectively employed in metal-free syntheses of biaryls (see Sect. 4.2.1). The synthetic strategy has been employed, for example, in the synthesis of polyfluorinated At21X [81] and acid-labile boron-substituted diaryliodonium salts firom aryl boronates with HTIB or the reagent combination PIFA/AcOH (Scheme 4a) [82]. Suna and coworkers have recently described the synthesis of heteroaryl(aryl)iodonium salts from heteroarenes and [hydroxy(tosyloxy)iodo] mesitylene or DIB combined with TsOH or AcOH. The salts were either isolated or used in situ (see Sects. 3.1.2 and 3.2.2) because of their relative instability [83, 84]. (Diacetoxyiodo)arenes were recently combined with electron-donating arenes and trimethylsilyl triflate (TMSOTf) to provide unsymmetric iodonium trifiates without the need for acid addition [85]. 

Cross-coupling of Boronic Acids. Ag20 can significantly enhance the reactivity of various boronic acids in Suzuki-Miyaura cross-coupling reactions. Alkylboronic acids, which, oftentimes, lead to poor conversions of the desired coupled product, are rendered more reactive by the addition of Ag20 (eq 24). Use of excess Ag20 facilitates the cross-coupling of various unactivated w-alkylboronic acids to either aryl or alkenyl halides/trifiates. The reaction conditions are very mild and furnish excellent yields of the desired coupled product. 

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