Pyridyl triflate

Little information has appeared on derivatives of [l,2,3,5]thiatriazolopyridines as mentioned also in CHEC-11(1996) <1996CHEC-II(8)405>. In a recent study, the thermal decomposition of the sulfoxide derivative 44 in methanol in the presence of sodium triflate was investigated <1996JFC161> (Scheme 13). After a prolonged reflux, two products 2-pyridyl triflate 46a and 2-methoxypyridine 46b, was isolated in 34% and 16% yields, respectively. The authors concluded that the first step of this transformation is a thermal ring opening of 45 to a carbene intermediate. 

Reaction of iV-fluoropyridinium triflate with a base in methylene chloride affords 2-chloropyridine as the major product along with 2-pyridyl triflate and 2-fluoropyridine. This conversion may be explained by a singlet carbene produced through proton abstraction of the fV-fluoropyridinium salt <1996JFC161>. 

Hexamethylditin is a suitable reagent for Pd-catalyzed metallation of aryl-halides to furnish aryltin compounds that in turn can react in Stille couplings with aryl halides to form biaryl derivatives. Hitchcock and coworkers [ 126] have shown that 2-pyridyl triflate and (hetero)aryl bromides can be coupled to 2-(hetero)aryl pyridines 174 in moderate to good yields (Scheme 66). The underlying principle of this heterocoupling of two aryl (pseudo)hahdes is the selective stannylation of the triflate that is undergoing a faster oxidative addition to the Pd(0) complex than the bromide. 

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 triflate, aryl or heteroaryl bromides, and hexamethylditin with Pd(PPh3)4 the presence of LiCl to give azabiai yls (Scheme 4-48). 

The coupling of a bromopyridine and an aryl bromide with hexamethylditin in the presence of a palladium catalyst has generated various diarenes in one pot.46 2,3 -Bipyridine, (2), was synthesized in 59% yield by a modification of this method that used hexamethylditin to couple pyridyl triflates with aryl bromides 47... 

C. 5-Methyl-2,2 -bipyridine (3). The 4- and 6-methyl-2,2 -bipyridines may also be prepared using the following procedure. A 500-mL, two-necked, round-bottomed flask (Note 2) with a Teflon-coated magnetic stirrer is placed in a dry ice/acetone bath (-78°C), then 80 mL of tetrahydrofuran (THF) (Note 11) and tert-butyllithium (tert-BuLi) (1.75 M in pentane, 52 mL, 91.0 mmol) Note 12) are added to it, followed by dropwise addition of 2-bromopyridine (7.13 g, 4.3 mL, 45.1 mmol) (Note 13). The canary yellow THF solution becomes reddish-brown upon addition of the pyridyl bromide. After the solution is stirred at -78°C for 30 min, anhydrous zinc chloride (ZnCI2) (13.3 g, 97.4 mmol) (Note 14) is added, and the reaction is stirred at 25°C for 2 hr. The 5-methyl-pyridyl triflate (2) (8.95 g, 37.1 mmol), lithium choride (LiCI) (3.18 g, 75.2 mmol) Note... 

Methyl-2-pyridyl triflate Methanesulfonic acid, trifluoro-, 4-methyl-2-pyridinyl ester (13) (179260-78-7)... 

In a model study [50], 2-[2-(4-phenyl-3-amino)-pyridyl]quinoline 119 was derived from the Stille coupling of 2-trimethylstannylquinoline 41 and pyridyl triflate 118. As an extension of the aforementioned method, decorated 2-trimethylstannylquinoline 120 was coupled with a more intricate pyridyl triflate 121 in the presence ofY C, to assemble adduct 122 in 68% yield [49]. Addition of Cu2Br2 is supposed to promote the rate of transmetalation. 2-Aryl-quinoline 122 was an advanced intermediate for the total syntheses of Streptonigrin [51 ] and Lavendamycin [52], which have been shown to possess antitumor and antiviral activities [51]. 

Pyridyl triflates in the benzenoid 3-position readily couple with terminal acetylenes (88JOC386). When the phenylacetylene is substituted in the phenyl ring by an o-amino group, the alkynylated product (56) can be cyclized by Pd(II)-catalysis to an indole, in this case to 2-(3-pyridyl)indole (89TL2581). 

The cross-coupling of aryl triflates and halides in the presence of hexamethylditin is a tandem process. From pyridyl triflates, the formation of pyridylstannanes is implied. 

The most recent successful method for generating 3-pyridynes uses 4-trialkylsilyl-3-pyridyl triflates as precursors (a similar approach but with a bromine in place of the triflate group is considerably less successful). They were synthesized by o-metallation... 

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