Heteroaryl triflates

An interesting class of covalent tnflates are vinyl and aryl or heteroaryl triflates Vinyl tnflates are used for the direct solvolytic generation of vinyl cations and for the generation of unsaturated carbenes via the a-elimination process [66] A triflate ester of 2-hydroxypyndine can be used as a catalyst for the acylation of aromatic compounds with carboxylic acids [109] (equation 55)... 

Bromo-4-[2-[(l,l-dimethylethoxycarbonyl)amino]phenyl]-5,8-dime-thoxyquinoline [CuBr to accelerate a chemoselective reaction between an aryltin and a heteroaryl triflate] [58]. 

Vinylation of heteroaryl triflates also possible. Vinyl halides can be coupled to alkenes to form dienes. " The reaction of dihydrofurans with vinyl triilates and a palladium catalyst leads to a nonconjugated diene, 33. This example illustrates that the product is formed by an elimination step, as with the Heck reaction (13-10), and double bond migration can occur resulting in allylic rearrangement. 

TABLE 5. PdCl2(PPhj)2-Catalyzed Homocoupling of Aryl and Heteroaryl Triflates in the Presence of Zn and Under Electroreductive Conditions... 

Buchwald reported an improved catalyst system for the palladium-catalyzed fluorination of aryl and heteroaryl triflates a pyrrole substrate similar to 98 was converted to the corresponding fluoride in 71% yield. Although a side-chain reaction for pyrrole, the fluorination was used... 

Cross-coupling reactions of alkynes. Terminal alkynes undergo high yield Pd(0) catalyzed coupling reaction (72-76) with organic electrophiles. The electrophiles include vinyl, aryl, and heteroaryl halides (72-75) vinyl triflates (77J8) aryl (56,78) and heteroaryl triflates (75,78) and polyfluorophenyl perfluoroalkane sulfonates (79). Several examples are shown in equation 23 - 27 (respectively references 78,72,73,78,79). 

Aryl, heteroaryl, and alkenyl cyanides are prepared by the reaction of halides[656-658] or triflates[659,660] with KCN or LiCN in DMF, HMPA, and THF. Addition of crown ethers[661] and alumina[662] promotes efficient aryl and alkenyl cyanation. lodobenzene is converted into benzonitrile (794) by the reaction of trimethylsiiyl cyanide in EtiN as a solvent. No reaction takes place with aryl bromides and chlorides[663]. The reaction was employed in an estradiol synthesis. The 3-hydroxy group in 796 was derived from the iodide 795 by converting it into a cyano group[664]. 

If the stannane bears substituents at the position geminal to tin, the reaction requires activation by Cu1 (Section 9.6.3.2.1). The cross-coupling of aryl (or heteroaryl) stannanes with aryl (or heteroaryl) halides or triflates is a general route to various biaryls and their analogues, particularly useful in those cases when the Suzuki-Miyaura reaction is less effective for... 

The scope of the SH reaction encompasses sp-sp2 (alkenyl, aryl (29),143 heteroaryl) and sp-sp couplings (the modified Cadiot-Chodkiewicz reaction).142 Iodides are most frequently used as electrophilic coupling partners, though the use of bromides, triflates (30),144 or even some reactive chlorides (31)145 is also possible. Due to the low steric bulk of the acetylenic unit, as well as its exceptional ability in the transduction of electronic effects, the SH reaction is well suited for construction of new (e.g., star-like) molecular architectures through polysubstitution (32).146... 

Tributylstannyl)-3-cyclobutene-1,2-diones and 4-methyl-3-(tributylstan-nyl)-3-cyclobutene-l,2-dione 2-ethylene acetals undergo the palladium/copper-catalyzed cross coupling with acyl halides, and palladium-catalyzed carbon-ylative cross coupling with aryl/heteroaryl iodides [45]. The coupling reaction of alkenyl (phenyl )iodonium triflates is also performed by a palladium/copper catalyst [46],... 

An application of Stille couplings to the solid phase using a traceless A-glycerol linker with 2-stannylindoles has been developed [177]. Only a few examples of the use of 3-stannylindoles in Stille reactions have been described. Ortar and co-workers prepared 169 and 170 and effected Pd-catalyzed cross coupling reactions with several aryl, heteroaryl, and vinyl substrates (bromides, iodides, triflates) to give the expected products 171 in high yields [178]. Enol triflates behave exceptionally well under the Ortar conditions, e.g., 172 to 173. 

A particularly elegant domino Heck reaction involving 4-bromoindole and bromo(indolyl)maleimide 251 to give N-methylarcyriacyanin A (252) in one operation was reported by Steglich [173]. This alkaloid could also be prepared from triflate 253 in higher yield in a heteroaryl Heck reaction. 

Like most aryl halides, furyl halides and furyl triflates have been coupled with a variety of organostannanes including alkenyl, aryl, and heteroaryl stannanes in the presence of catalytic palladium. Carbamoylstannane 66 was prepared by treating lithiated piperidine with carbon monoxide and tributyltin chloride sequentially. The Stille reaction of 66 and 3-bromofuran then gave rise to amide 67 [61]. In another example, lithiation of 4,4-dimethyl-2-oxazoline followed by quenching with MesSnCl resulted in 2-(tributylstannyl)-4,4-dimethyl-2-oxazoline (68) in 70-80% yield [62], Subsequent Stille reaction of 68 with 3-bromofuran afforded 2-(3 -furyl)-4,4-dimethyl-2-oxazoline (69). 

TABLE 6. Cross-coupling between alkyl Grignard reagents and aryl or heteroaryl chlorides, triflates, and tosylates... 

---