Aromatic triflates, palladium-catalyzed

The palladium-catalyzed arylations of aromatic carbonyl compounds such as ketones,67,67a amides (Equation (60)),68 and aldehydes69 with aryl halides and triflates give the multiple arylation products similarly. 

Intramolecular arylation of G-H bonds gives cyclic aromatic compounds. In this intramolecular arylation, the carbon-palladium cr-bond is first formed by the oxidative addition of Pd(0) species and then the resulting electrophilic Pd(n) species undergoes the intramolecular G-H bond activation leading to the formation of the palladacycle, which finally affords the cyclic aromatic compounds via reductive elimination.87 For example, the fluoroanthene derivative is formed by the palladium-catalyzed reaction of the binaphthyl triflate, as shown in Scheme 8.88 This type of intramolecular arylation is applied to the construction of five- and six-membered carbocyclic and heterocyclic systems.89 89 89 ... 

Most of the work on the C-N bond-forming crosscoupling reactions has concentrated on the formation of aromatic C-N bonds. Recent studies show that the application of cross-coupling reactions to alkenyl halides or triflates furnished enamines (Scheme 19) (for palladium-catalyzed reaction, see 28,28a-28d, and for copper-catalyzed reaction, see 28e-28g). Brookhart et al. studied the palladium-catalyzed amination of 2-triflatotropone 109 for the synthesis of 2-anilinotropone 110.28 It was found that the reaction of 109 proceeded effectively in the presence of racemic BINAP and a base. As a simple method for the synthesis of enamines, the palladium-catalyzed reactions of alkenyl bromide 111 with secondary amine were achieved under similar conditions.2841 The water-sensitive enamine 112 was isolated as pure compound after dilution with hexane and filtration through Celite. The intramolecular cyclization of /3-lactam 113, having a vinyl bromide moiety, was investigated by Mori s... 

The palladium-catalyzed arylation and alkenylation of terminal alkynes with aryl or alkenyl hahdes in presence of a copper(l) co-catalyst is called Sonogashira reaction. In the same way as in the other cross-coupling reactions described before, it is possible to immobihze the alkyne or the aromatic bromides, iodides or triflates on sohd supports (Scheme 3.15). 

While die above reactions represent only a small fraction of die reactions known for palladium, they form the basis of a powerful methodology for building carbon structures. Several variations have been developed which utilize certain types of reactants and give particular types of products. All diese variations, however, contain a common theme. In each case an electron-deficient reagent (e.g., a vinyl halide or aromatic triflate) reacts with an election-rich reagent (e.g., an alkene, an organoborane, or an organotin) witii the formation of a new carbon-carbon bond. In that sense diese reactions are related to die reactions between carbon nucleophiles and carbon electrophiles discussed previously in diis chapter. They are quite different, however, because diey proceed only in the presence of Pd(0). In fact they proceed only in die coordination sphere of Pd(0). The ability of Pd(0) to catalyze diese reactions is nearly unique We will now examine some of die more common processes. 

Palladium catalyzed aminations of aryl halides and triflates have become a very elEcient and useful method for the synthesis of aromatic amines (Scheme 33) [243-248],... 

Palladium-catalyzed annulations of terminal alkynes by functionally substituted aromatic or vinylic halides or triflates often employ copper salts and most likely proceed by initial cross-coupling to produce the corresponding aryl alkyne or enyne (Eq. 1). 

Biscoe disclosed a novel stereoretentive palladium-catalyzed Stille crosscoupling reaction of aryl halides with secondary alkyl azastannatranes.The reported reaction tolerates a range of aryl chlorides, bromides, iodides, and triflates minimal amounts of isomerization of the alkyl group are observed. A variety of aromatics and heteroaromatics are compatible with the given conditions and pyrrole 98 was converted to derivative 100 in 66% yield (13NC607). 

One of the first reports of a microwave-assisted palladium-catalyzed reaction for the formation of an arylphosphine oxide described the synthesis of progesterone antagonists (Scheme 4.198) [335]. The chemistry was based upon functionalization of the aromatic group on the lip-position of the steroid core. An aryl triflate and a secondary phosphine... 

Heating 2-amidofuran 253 at 165 °C was reported to give the phenolic indoline 252 in 87% yield, and this occurs by elimination of thiophenol from the initially formed cycloadduct. The cycloaddition behavior of the thermally more robust iV-ethyl carbamate derivative 255 proceeded quite smoothly to furnish phenol 254 in 80% yield when heated at 160 °C for 7h. It should be noted that the phenolic functionality present in the aromatic ring of indolines 252 and 254 has the potential to be transformed into an aryl triflate and used for palladium-catalyzed cross-coupling chemistry to afford more highly functionalized products (Scheme 13.58) [102]. 

Several reports have been made of a successful catalyzed addition/ substitution reaction resulting in direct attachment of phosphorus to aromatic rings. The preparation of mixed triarylphosphines has been accomplished by the reaction of tin- or silicon-substituted diphe-nylphosphines with aryl halides catalyzed by palladium reagents.74 A similar transformation has also been reported using nickel catalysis.75 The addition/substitution of diphenylphosphine to triflate functionalized phenolic linkages has been of use for the preparation of substances as analogues of tyrosine-related amino acid derivatives, accomplished with catalysis by palladium acetate (Equation 4.29).76... 

Selective palladium(0)-catalyzed arylation can be performed with aryl iodides bearing a triflate function using an appropriate palladium catalyst. Under these conditions, aromatic iodotriflates like 59 can play the role of multi-coupling reagents [88]. Thus, the reaction of 59 with a functional arylzinc bromide provides the functionalized biphenyl triflate 60 (see Section 9.6.13 Scheme 9-48) [89]. 

---