Halides, aryl, arylation catalyzed

Formation of carboxylic acids ami their derivatives. Aryl and alkenyl halides undergo Pd-catalyzed carbonylation under mild conditions, offering useful synthetic methods for carbonyl compounds. The facile CO insertion into aryl- or alkenylpalladium complexes, followed by the nucleophilic attack of alcohol or water affords esters or carboxylic acids. Aromatic and a,/ -unsaturated carboxylic acids or esters are prepared by the carbonylation of aryl and alkenyl halides in water or alcohols[30l-305]. 

Palladium complexes also catalyze the carbonylation of halides. Aryl (see 13-13), vinylic, benzylic, and allylic halides (especially iodides) can be converted to carboxylic esters with CO, an alcohol or alkoxide, and a palladium complex. Similar reactivity was reported with vinyl triflates. Use of an amine instead of the alcohol or alkoxide leads to an amide. Reaction with an amine, AJBN, CO, and a tetraalkyltin catalyst also leads to an amide. Similar reaction with an alcohol, under Xe irradiation, leads to the ester. Benzylic and allylic halides were converted to carboxylic acids electrocatalytically, with CO and a cobalt imine complex. Vinylic halides were similarly converted with CO and nickel cyanide, under phase-transfer conditions. ... 

We studied the competitive amination of two amines (benzophenone hydrazone and -hexylamine) and one aryl halide (3-bromobenzotrifluoride), catalyzed by Pd(BlNAP). We showed that, when reacting alone at the same conditions, n-hexylamine is considerably more reactive and shows positive order kinetics benzophenone hydrazone shows zero order kinetics and forms a very stable intermediate, the BlNAP(Pd)Ar(amine) we also observed by NMR. During the competitive reaction of the two amines, the benzophenone hydrazone reacts first and only when it is completely consumed, the hexylamine starts to react. In this case it is the stability of the major intermediate, and not the relative reactivity, which dictates the selectivity. 

As noted in Section 11.2.2, nucleophilic substitution of aromatic halides lacking activating substituents is generally difficult. It has been known for a long time that the nucleophilic substitution of aromatic halides can be catalyzed by the presence of copper metal or copper salts.137 Synthetic procedures based on this observation are used to prepare aryl nitriles by reaction of aryl bromides with Cu(I)CN. The reactions are usually carried out at elevated temperature in DMF or a similar solvent. 

Intramolecularly coordinated A1 and In compounds (e.g., (75), (76)) transfer the Me group in cross-coupling reactions with various aryl halides, including chlorides, catalyzed by Pd and Ni complexes.16 262 265 Monoorganobismuth compounds are reactive in cross-coupling reactions only if they contain an intramolecularly coordinating residue (77),266 267... 

With the exception of intramolecular amination reactions, all of the early aryl halide aminations were catalyzed by palladium complexes containing the sterically hindered P(o-tol)3. In papers published back-to-back in 1996, amination chemistry catalyzed by palladium complexes of DPPF and BINAP was reported.36,37 These catalysts allowed for the coupling of aryl bromides and iodides with primary alkyl amines, cyclic secondary amines, and anilines. 

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],... 

Reaction of organic halides with alkenes catalyzed by palladium compounds (Heck-type reaction) is known to be a useful method for carbon-carbon bond formation at unsubstituted vinyl positions. The first report on the application of microwave methodology to this type of reaction was published by Hallberg et al. in 1996 [86], Recently, the palladium catalyzed Heck coupling reaction induced by microwave irradiation was reported under solventless liquid-liquid phase-transfer catalytic conditions in the presence of potassium carbonate and a small amount of [Pd(PPh3)2Cl2]-TBAB as a catalyst [87]. The arylation of alkenes with aryl iodides proceeded smoothly to afford exclusively trans product in high yields (86-93%) (Eq. 61). 

Zask, A. Helquist, P. Palladium hydrides in organic synthesis. Reduction of aryl halides by NaOMe catalyzed by Pd(PPh3)4. /. Org. Chem. 1978, 43, 1619-1620. 

Table 7.5. Reactions of aryl halides with azoles catalyzed by Pd(0)/P(/-Bu)3...

The amination of aryl halides and triflates catalyzed by palladium complexes is suitable for use in complex synthetic problems. Many substrates will produce high yields of mixed arylamines with one of the existing catalyst systems. Nevertheless, there are many combinations of substrates for which the amination chemistry may be substantially improved. For the most part, these reactions involve nitrogen centers, such as those in pyrroles, indoles, amides, imidazoles and other heterocyclic groups that are less basic than those in standard alkylamines. Although mild reaction conditions have been developed for many substrates, the harsh conditions used in many of the applications indicate that continued studies on developing mild condi-... 

Diaryliodonium salts are viable alternatives to aryl halides for palladium-catalyzed cross-coupling reactions (02CRV2523). In the area of heterocyclic synthesis, Pd(II)-catalyzed carbonylation of diaryliodonium... 

Allylindium reagents can be utilized in the Pd-catalyzed cross-coupling reaction with aryl halides. The Pd-catalyzed allylic substitution of allyl carbonate produces 1,5-dienes (Scheme 103).353-355... 

Carbon—carbon coupling reactions of aryl halides are commonly catalyzed by palladium triarylphosphine complexes and proceed well for aryl bromides and iodides while aryl chlorides are generally unreactive. More basic chelating trialkylphosphines, however, render palladium sufficiently electrophilic to undergo rapid oxidative addition with chlorobenzene ... 

After Kumada and Tamao and Corriu independently reported the nickel(II) salts-and complexes-catalyzed cross-coupling reaction of Grignard reagents with aryl and alkenyl halides, the Pd-catalyzed reaction of Grignard reagents was first reported by Murahashi. ... 

It is a palladium-catalyzed cross-coupling reaction between organosilanes (vinyl, ethynyl and allylsilanes) and organic halides (aryl, vinyl and allyl halides). Allylpal-ladium chloride dimmer [( ri -C3H5PdCl)2] and either tris(diethylamino)sulfonium difluorotrimethylsilicate (TASF) or tetra-n-butylammonium fluoride (TBAF) are used as catalysts. Fluoride ion acts as an activator for the coupling, forming an intermediate hypervalent anionic silicon species, which can then transmetallate with palladium as a preliminary reaction to coupling. 

Double Carbonylation of Aryl Halides. (DIOP)PdCl2 catalyzed the double carbonylation of phenyl iodide in the presence... 

The order of reactivity of aryl or alkenyl halides in Pd-catalyzed crosscouplings is I > Br > Cl. The preparation of enediynes by a Sonogashira coupling, however, is usually carried out with cw-dichloroethylene as the substrate yields are considerably poorer when cfs-dibroniocthylcnc is used instead. Why (Hint The key intermediate may be more prone to undergo what side reaction when the dibromide or diiodide is used )... 

Carboxylic acid derivatives. Homologation of aryl and heteroaryl halides by the catalyzed carbonylation in the presence of amines leads to amides. For the preparation of primary amides, hexamethyldisilazide provides the amino group. ... 

Without any catalyst, organotin enolates react with allylic halides to afford the monoallylation products (eq (122)) [117]. Alkenyl halides, aryl halides, and allylic acetates can be used for the alkylation of tin enolates when the reactions are catalyzed... 

Palladium and copper-catalyzed arylation of C-H bonds by aryl halide reagents is reviewed. The emphasis of the review is on directing-group-containing arene and alkane arylation catalyzed by palladium and on sp2 C-H bond arylation catalyzed by copper. Literature up to early 2009 is covered. 

The mechanism of the amines or alcohols arylation catalyzed by nickel(II) complexes has not been elucidated until now (refs. 7, 17), even though the arylation of nucleophiles catalyzed by nickel(0) complexes is better understood. In this last case it is generally admitted that the reaction proceeds by an oxidative addition step, followed by a nucleophilic substitution, and then a reductive elimination of the arylation product (Scheme 4). According to the work of Kochi (ref. 18), the oxidative addition of the haloarene on a nickel(O) complex takes place through a monoelectronic transfer from the metal to the aryl halide with simultaneous formation of a nickel(I) intermediate, the actual catalyst of the reaction (ref. 6). 

The first attempt to couple aryl halides with ammonia catalyzed by copper/ligand was reported by a Merck group (Scheme 9.1) [15]. In this case ethylene glycol may serve as both ligand and solvent, and the reaction proceded at 80 °C under elevated pressure. Mild conditions were discovered by Kim and Chang, in which L-proHne (LI) was employed as the ligand (Scheme 9.2) [16]. Both NH4CI and NH3-H20... 

Among many substrates used for Pd(0)-catalyzed reactions, organic halides are most widely used. In Grignard reactions, Mg(0) metal reacts with organic halides of sp carbons (alkyl halides) more easily than halides of sp carbons (aryl and alkenyl halides). On the other hand, Pd(0) complexes react more easily with halides attached to sp carbons, namely aryl and alkenyl halides. In addition, several pseudohalides are used as well. They undergo facile oxidative addition to Pd(0) to form Pd complexes which have cr-Pd-carbon bonds. Scheme 3.1 summarizes the oxidative addition of phenyl halides and pseudohalides to form phenylpalladium halides. Aryl iodides and bromides have been used widely. 

A well-established method for the synthesis of internal alkynes 34 is the Pd/Cu-catalyzed coupling of vinyl halides, aryl iodides, bromides, or triflates with terminal acetylenes 33 (Scheme 12). Nevertheless, this method suffers not only from the need for large amounts of catalyst (1-5 mol % Pd and 1-10 mol % Cul) but also from the need of higher temperatures for the aryl bromides. 

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