Triflates palladium-catalysed coupling reactions

Pyridazine triflates are readily prepared in high yield by reaction of triflic anhydride either with 3(2//)-pyridazinones in pyridine at room temperature or with the lithium salts in THE at — 78°C (Equation (26)). These triflates, which are white crystalline solids stable at 0°C, are useful in palladium catalysed coupling reactions <94H(38)1273>. 

Thiols have been employed as nucleophiles in palladium-catalysed coupling reactions (Scheme 2.181). An aryl thioether could be formed from an aryl triflate using a strong base, a bidentate ligand and a nonpolar solvent to suppress competitive triflate decomposition. An intramolecular thiol coupling with an iodoindole was a key step in a synthesis of chuangxinmycin (Scheme 2.182). ... 

Organozinc reagents, including the Reformatsky reagents, are extensively used in transition metal catalysed coupling reactions with aryl halides or triflates, vinyl halides, and allylic halides or acetates, as reviewed by Erdik156. Nickel and palladium complexes are... 

It has been found that the use, as ligands, of electron-poor phosphines, such as 1,1 -bis(diphenylphosphino)ferrocene, enhances yields ill the palladium-catalysed reaction of aiyl bromides with sodium phenoxides to yield diaryl ethers.87 Palladium-catalysed coupling of ethynylated derivatives of bipyridine or terpyridine with the corresponding bipyridine or terpyridine hahdes or triflates has been used in the synthesis of preorganized polytopic ligands.88... 

The reaction was exploited very recently in a solid phase synthesis of biaryls. Aryl zinc bromides undergo palladium catalyzed coupling reactions with aryl bromides bound to a polystyrene resin. The product can be released from the resin by transesterification [44]. Ni(0) catalysed homocoupling of arylzinc reagents could also be realised using aryl triflates [45], as well as aryl tosylates and mesylates [46]. 

Heteroaryl halides (or phenolic triflates) take part in palladium-catalysed couplings with a wide range of organometallic and anionic reagents in contrast to the Heck reaction, the catalyst is often provided as preformed Pd(0), in a complex such as tetrakis(triphenylphosphine)palladium(0), Pd(Ph3P)4. 

Palladium- (and nickel-) -catalysed coupling reactions proceed normally on halodiazines and the equivalent triflates, the most significant feature being the enhanced reactivity relative to chlorobenzenes of chlorine at position a and 7 to a nitrogen, just as in pyridine chemistry. In some particularly activated caes, this extra activation is sufficient to overcome the normally higher reactivity of bromine, but not... 

Bromo- and -iodoindoles, and the similarly reactive 2- and 3-triflates, " undergo palladium-catalysed couplings as normal aryl halides. Since 2- and 3-haloindoles are unstable it is expedient to employ their A -acyl derivatives. Halogen and triflate on the benzene ring of indoles take part unexceptionally in coupling reactions. 

Proazaphosphatrane bases were used for palladium catalysed Stille reactions of aryl chlorides. These bases efficiently catalyse the coupling of electronically diverse aryl chlorides with an array of organotin reagents. The catalyst system based on benzyl (Bn)-proazaphosphatrane is active for the synthesis of sterically hindered biaryls. The use of the proazaphosphatrane allows room temperature coupling of aryl bromides and it also permits aryl triflates and vinyl chlorides to participate in Stille coupling [69] (Scheme 5.47). 

Indoles with carbocyclic halogen or triflate substituents are potential starting materials for vinylation, arylation and acylation via palladium-catalysed pro-cesses[l]. Indolylstannanes. indolylzinc halides and indolylboronic acids are also potential reactants. The principal type of substitution which is excluded from such coupling reactions is alkylation, since saturated alkyl groups tend to give elimination products in Pd-catalysed processes. 

A useful method for the preparation of functionalised thiazoles has been described. Palladium catalysed cross coupling reactions between 4-thiazolyl-5-acetyl triflates 36 and alkynes afforded 4-alkynyl-5-acetylthiazoles 37 in good yields (56-82%). If 37 is then treated with ammonia in methanol, thiazolo[5,4-c]pyridines 39 are formed, probably via the intermediate imine 38 which then undergos a regioselective 6-endo dig cyclisation <99EJOC3117>. 

Palladium catalysts have been found which are effective in the Suzuki coupling reaction of arylboronic acids with aryl chlorides carrying electron-withdrawing groups.73 Biaryls may also be synthesized by cross-coupling of arylboronic acids with arenediazonium salts.74,75 There has been a report of the polymer-bound palladium-catalysed Suzuki coupling of aryl triflates with organoboron compounds.76 Arylbor-onates may themselves be synthesized by the palladium-catalysed reactions of... 

The Suzuki Coupling, which is the palladium-catalysed cross coupling between organoboronic acid and halides. Recent catalyst and methods developments have broadened the possible applications enormously, so that the scope of the reaction partners is not restricted to aryls, but includes alkyls, alkenyls and alkynyls. Potassium trifluoroborates and organoboranes or boronate esters may be used in place of boronic acids. Some pseudohalides (for example triflates) may also be used as coupling partners. 

The palladium-catalysed cross-coupling of aryl halides or vinyl halides with dialkyl phosphonates (31) to yield dialkyl arylphosphonates and dialkyl vinylphosphonates, respectively, was first reported by Hirao and co-workers 69 the halides used most frequently are bromides and the reaction is stereospecific with haloalkenes. Subsequently, analogous reactions of alkyl alkylphosphinates (32), alkyl arylphosphinates (32), alkyl phosphinates (33), and secondary phosphine oxides (34), replacing [P—H] bonds with [P—C] bonds to yield various phosphinates and tertiary phosphine oxides, have been developed (Figure 7.1). Alkyl phosphinates (33) may be mono- or diarylated as desired by the selection of appropriate conditions. Aiyl and vinyl triflates have also found limited... 

Hi. Carbon-silicon bonds. Following the earlier reports mentioning the palladium-catalysed addition of organosilylstannanes to alkynes or isonitriles , Mori and coworkers realized tandem transmetallation-cyclization reactions with bifunctional halogeno triflates and Bu3SnSiMe3 18. The reactivity of 18 under palladium catalysis was used for the silylstannylation of alkenes or the synthesis of allylic silanes via a three-component (aryl iodide - - diene - - 18) coupling reaction. Recently, a similar... 

The cross coupling reactions of aryl halides or aryl triflates with arylmetals catalysed by palladium(O) has found extensive use in the synthesis of unsymmetrical biaryls (ref. 27). A recent application of this coupling approach in the presence of chiral planar chromium complexes (ref. 25) has proved fruitful in the synthesis of chiral biaryls. Furthermore, Cr(CO)3-complexed biaryls can be isomerised under thermodynamic control, providing access to both atropisomers. Heating a solution of the complexed biaryl 37 in xylene under reflux resulted in a 1 99 ratio favouring the isomerised biaryl chromium complex 38 (ref. 28)... 

Halopyridines or pyridinyl triflates take part in palladium-catalysed reactions -Heck, carbonylation, and coupling reactions, for example with alkynes, or in Suzuki reactions with arylboronic acids,and cyclopropylboronic acids. 

The mechanism of palladium-catalysed cross-coupling starts, as in the Heck reaction, with oxidative addition of the halide or triflate to the initial palladium(O) phosphine complex to form a palladium(ll) species. But the next step is new it is a transmetallation, so-called because the nucleophile (Ri) is transferred from the metal in the organometallic reagent to the palladium and the counterion (X=hallde or triflate) moves in the opposite direction. The new palladium(ll) complex with two organic ligands undergoes reductive elimination to give the coupled product and the palladium(O) catalyst, ready for another cycle. 

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