Buchwald aryl triflates

Wolfe, J. and Buchwald, S. Palladium-catalyzed amination of aryl triflates. J. Org. Chem. 1997, 62, 1264-1267. 

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). 

It was envisioned that the attachment of a functionalized aromatic group could be done via a Buchwald-Hartwig reaction (Scheme 11). This reaction was first studied using diphenethylamine with aryl triflates and halides as model compounds. Diphenethylamine was... 

Later that year, the Ahman and Buchwald reported an improved procedure for the reaction of triflates and cyclic secondary amines [82]. The use of CS2CO3 as base allowed numerous electron-deficient aryl triflates to be coupled in high yield. The reaction between the 4-cyano-substituted aryl triflate and morpholine in the presence of ( )-BINAP/Pd provided the desired arylamine in 28% yield, Eq. (57). However, when the triflate was added over the course of 30 minutes, the desired product was isolated in 60% yield. The use of CS2CO3 as base improved the yield of arylamine to 84 %. The use of a mild base also allowed for the use of functionalized aryl triflates in the C-N bond forming reaction. 

Wolfe and Buchwald reported that the arylation of ahphatic amines with aryl triflates could be effected with the BINAP/Pd-catalyst [80]. Triflate cleavage was a common side reaction, thus, slow addition of the aryl triflate often resulted in improved yields of the desired compound. 

Wolfe and Buchwald susbsequently reported that by use of a milder base such as CsjCOj resulted in significant improvements in yield, particularly in the cases with electron-poor aryl triflates [82]. 

Aryl triflates are also good substrates for the benzophenone imine coupling reaction. For example. Singer and Buchwald prepared the desired amino-BlNOL precursor in 87% yield after acidic hydrolysis the amination itself proceeded in 90% NMR yield when DPEphos (19) was used as the supporting ligand, Eq.(132) [107]. 

The Buchwald-Hartwig amination reaction has become a most efficient method for forming a new C-N bond, and it is mediated by a Pd catalyst. Onr group reported on the nse of 1 to catalyze amination reactions of aryl triflates with very good results (Table 14.5). ... 

Buchwald-Hartwig Amination Reactions with Aryl Triflates Using 1... 

The palladium catalyzed amination of aryl triflates has proved to be a more challenging problem. Aryl triflates are less favored to undergo oxidative addition as compared to aryl bromides and iodides. Another, more daunting, challenge with aryl triflates is their proclivity to react with NaOt-Bu at sulfur to give a sodium phenoxide as the major by-product. Buchwald s laboratory reported that with fairly electron rich (EDG) and neutral aryl triflates, they could use NaO/-Bu as a base with minor amounts of... 

A solid reagent itself such as a metal, metal oxide, or metal salt, can be fixed in a packed-bed reactor. Buchwald and co workers developed a CsF packed-bed reactor for the Pd-catalyzed conversion of aryl triflates to aryl fluorides in flow. It is very important to achieve a uniform flow distribution in the packed bed. To this end, they prepared a microreactor filled with finely ground CsF that had been filtered to obtain a uniform particle size distribution of approximately 45-106 pm. By using the packed-bed reactor, a variety of (hetero)aryltriflates were converted into the corresponding aryl fluorides in the presence of a catalytic amount of homogeneous Pd(0) catalyst within short reaction times under flow conditions (Scheme 7.8). The... 

Buchwald and co-workers successfully developed a catalytic fluorination of aryl triflates in 2009 using [(cinnamyl)PdCl]2 as the catalyst, f-BuBrettPhos (LI), a bullq biaiylphosphine ligand, and caesium fluoride as the fluoride salt. The success of this coupling relied on the formation of a reactive monomeric 14-electron intermediate 5, which was susceptible to reductive... 

BuchwaM-Hartwig and Related Reactions. The Pd(OAc)2-catalyzed Buchwald-Hartwig-type couplings of both electron-poor and electron-rich aryl triflates have been shown to proceed efficiently with various amines provided the appropriate base is used. NaOfBu is usually employed for electron-rich systems while CS2CO3 is preferred for electron-deficient and neutral species (eq 130). ... 

The smooth palladium-catalyzed conversion of aryl triflates into aryl bromides and chlorides has been described by the Buchwald group in 2010. The protocol makes use of a bulky Lewis acid (triisobutyl aluminum) combined with a PEG as a phase transfer catalyst (Scheme 5-171). Fluorides can also be synthesized from triflates, also shown by the Buchwald group. ... 

The coupling between an aryl halide or triflate and an amine is known as the Buchwald-Hartwig amination [138]. Originally it was described using a tributyltin amine [139,140] and was thus considered to be a coupling reaction. Subsequently, tributyltin amine was replaced by a standard amine and a strong base. It is a reaction of great academic and industrial interest [11]. 

In terms of methodologies for the preparation of A-arylindoles 140, Buchwald reported improved conditions for the palladium-catalyzed coupling of aryl chlorides, bromides, iodides and triflates 138 with a variety of 2-, 7- and polysubstituted indoles 139 utilizing novel electron-rich biaryl(dialkyl)phosphine ligands in combination with Pd2(dba)3 <00OL1403>. Alternatively, Watanabe reports similar A-arylations of pyrrole, indole and carbazoles with aryl bromides and chlorides using Pd(OAc)2/P(f-Bu)3 in xylene at 120°C <00TL481>. 

The Pd-catalyzed intermolecular C—O bond formation has also been achieved [105-108]. Novel electron-rich bulky phosphine ligands utilized by Buchwald et al. greatly facilitated the Pd-catalyzed diaryl ether formation [109], When 2-(di-tert-butylphosphino)biphenyl (95) was used as the ligand, the reaction of triflate 93 and phenol 94 elaborated diaryl ether 96 in the presence of Pd(OAc)2 and K3PO4. The methodology also worked for electron-poor, neutral and electron-rich aryl halides. 

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