Aryl derivatives triflates

There has been a summary of the use of insertion reactions of arynes into a-bonds to prepare nrt/io-disubs tituted arenes. A key to the success of these processes is the ability to generate benzyne under mild conditions by the reaction of readily available o-(trimethylsilyl)phenyl triflate with fluoride ions.61 Reaction of amines and their derivatives with benzynes generated in this way has been shown to be an efficient method for the production of N-arylated derivatives, as illustrated in Scheme 8. The method also works well in the O-arylation reactions of phenols and carboxylic acids 62... 

Alkenyl aryl iodonium triflates. By using alkynes to capture [PhlPJ OTL, which is derived from Phi and FXeOTf, mixed iodonium triflates are readily obtained. 

Addition of zinc(II) chloride to the lithium compound 4 gave the zinc derivative 6, which is stable even at 50 °C in tetrahydrofuran. The palladium-catalyzed coupling reaction of the zinc salt with vinyl iodides, vinyl triflates and aryl iodides produced vinyl and aryl derivatives 7 and 8 (Table 1, entries 11-16). Cerium derivatives of cyclopropenone acetals were prepared by addition of the lithium salt 4 to a suspension of anhydrous cerium(III) chloride in tetrahydrofuran at — 70 C. The resulting organocerium reagent coupled with oc-aminoaldehydes (Table 1, entry 17). ° ... 

The only reaction reported for this ring system is its methylation with methyl triflate. From the fully unsaturated derivative (192), the iV-methyl compound (193) can be obtained in fairly good yield (Equation (42)). Such reactions were also carried out with other 3-aryl derivatives <83JHC38i>. 

Piperidine, morpholine, pyrrolidine, N-alkylpiperazines, and anilines have been converted to N-aryl derivatives by use of aryl triflates under the action of microwave irradiation in NMP [58]. The amination reaction proceeded efEciently in the absence of base and catalyst, and was not affected by traces of water (Scheme 10.23). 

Besides the traditional coupling between alkenes and aryl (vinyl) halides, other functionalized aryl derivatives can also couple with alkenes in the Heck reaction, including aryl silanes,stannanes, bismuth, antimony,triflates, boric acid, phosphonic acid, carboxylic acid, and diazonium salt. ... 

Tin Reagents. The Af-protected triflyloxy derivative 41 of pyrrolo[2,3-d]pyrimidine when reacted with an arylstannane affords 5-aryl derivatives (Scheme 20). A closely related reaction has been used in the preparation of the 5-substituted ]S-2 -deoxyribo-sylpyrrolo[2,3-[Pg.423]

The oxidative addition of p-substituted aryl iodidesf f ° and triflates to Pd°(PPh3>4 follows a Hammett correlation with a positive slope and is thus faster for aryl derivatives substituted by electron-withdrawing groups. The following order of reactivity has been established in DMF at 20... 

However, compound 22 showed poor oral bioavailability (f =3%). Our efforts to identify compounds with good oral bioavailability by systematically varying the substitution pattern on the pyridine ring led to the discovery of Cg-aryl derivatives that, in general, had excellent potency and oral bioavailability. The synthesis of Cg-aryl derivatives was carried out by Suzuki reaction of the corresponding triflate or bromide (Figiu-e 19.7). From this subseries, compound 24 was identified as the first recommended development candidate that met all the development criteria [7]. 

Synthesis of 3,3-disubstituted oxindoles from arylation- and vinylation-carbocycUzation of electron-deficient alkenes with diaryliodonium salts catalyzed by CuCl catalyst was reported by Zhou, Li, and coworkers. A wide range of diaryl and vinyl(aryl)iodonium triflates and various substitutions on phenylacrylamides are compatible for this reaction. Both ( )-physostigmine and ( )-physovenine have been synthesized successfully in 41 and 36% overall yield using this vinyl addition/cyclization method [71]. Fu and coworkers developed a Cul-catalyzed synthesis of oxindole derivatives from readily available Af-alkyl-Af-phenylacrylamides and diaryliodonium triflates [72] (Scheme 8.34). 

Cross-coupling reactions between amines and aryl halides or pseudohalides have been employed for the preparation of a number of chiral, nonracemic ligands for asymmetric catalysis. For example, early studies by Buchwald illustrated that chiral amino binaphthol derivatives could be generated by Pd-catalyzed Af-arylation of binaphthol-derived triflates (Eq. 74) [417]. A similar strategy was employed by Erase for the synthesis of planar-chiral [2.2]paracyclophane ligands (Eq. 75) [418]. The A -arylation of [2.2]paracyclophane-derived triflates has also been used for the construction of planar-chiral benzimidazoles [419]. The IV-arylation of a substituted pyrrolidine with 4-bromopyridine played a key role in the synthesis of a chiral nucleophilic catalyst related to DMAP [420]. 

The most useful pseudo-halides are aryl triflates (trifluoromethylsulfonates) of phenols and enol triflates derived from carbonyl compounds[4,5,6]. 

Pyrrole derivatives are prepared by the coupling and annulation of o-iodoa-nilines with internal alkynes[291]. The 4-amino-5-iodopyrimidine 428 reacts with the TMS-substituted propargyl alcohol 429 to form the heterocondensed pyrrole 430, and the TMS is removed[292]. Similarly, the tryptophane 434 is obtained by the reaction of o-iodoaniline (431) with the internal alkyne 432 and deprotection of the coupled product 433(293]. As an alternative method, the 2,3-disubstituted indole 436 is obtained directly by the coupling of the o-alky-nyltrifluoroacetanilide 435 with aryl and alkenyl halides or triflates(294]. 

Carbonylation of enol triflates derived from ketones and aldehydes affords Q,/)-unsaturated esters[332]. Steroidal esters are produced via their aryl and enol triflates[328]. The enol triflate in 477 is more reactive than the aryl tritlate and the carbonylation proceeds stepwise. First, carbonylation of the enol triflate affords the amide 478 and then the ester 479 is obtained in DMSO using dppp[333]. 

Aldehydes can also be prepared by the carbonylation of aryl and alkenyl halides and triflate, and benzyl and allyl chlorides using tin hydride as a hydride source and Pd(PhjP)4 as a catalyst[377]. Hydrosilancs arc used as another hydride source[378]. The arenediazonium tetralluoroborate 515 is converted into a benzaldehyde derivative rapidly in a good yield by using Et ,SiH or PH MS as the hydride source[379]. 

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]. 

Of particular synthetic importance is the coupling of aryl- and hetarylboronic acids to aryl- and hetaryl halides (or triflates), allowing for a convenient synthesis of biphenyls, even sterically demanding derivatives such as 14, hetaryl phenyls and Zj/ -hetaryls. With appropriately disubstituted aromatic substrates, the Suzuki coupling reaction can be applied in the synthesis of polyphenylene materials. 

Ni(0)-mediated homocouplings of 2-subslituted l,4-phcnylenebis(triflate)s have been reported by Percec et al. [15] to provide substituted poly(/ -phenylene)s 7 containing alkyl, aryl or ester substituents in the 2- and 3-positions of the 1,4-phenylcnc skeleton. This method of preparation appears to be broad in scope, especially due to the ease of preparation of the bis(lriflatc) monomers starting from the corresponding hydroquinone derivatives. 

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