Palladium catalyzed biaryl coupling

Nishimura, M. Ueda, M. Miyaura, N. Palladium-catalyzed biaryl-coupling reaction of arylboronic adds in water using hydrophilic phosphine ligands. Tetrahedron 2002, 58, 5779-5787. 

Synthesis of analogues by palladium-catalyzed biaryl coupling... 

Conditions first described by Fagnou were used to affect the C-H to C-H bond cyclization, which proceeded in 47% yield. Mechanistically the direct coupling reaction is thought to proceed via intramolecular nucleophilic attack of the pyrrole moiety onto the Pd(II) centre. It was postulated that the electron rich DavePhos ligand facilitates both oxidative addition and forms a more reactive cationic Pd(II) species by dissociation of the halide. Following a deprotonation step, reductive elimination of Pd(0) then resulted in formation of the biaryl bond, completing the core framework. Application of this direct palladium-catalyzed biaryl coupling facilitates a very efficient and concise synthesis of rhazinilam as a racemate. 

Several microwave-assisted protocols for soluble polymer-supported syntheses have been described. Among the first examples of so-called liquid-phase synthesis were aqueous Suzuki couplings. Schotten and coworkers presented the use of polyethylene glycol (PEG)-bound aryl halides and sulfonates in these palladium-catalyzed cross-couplings [70]. The authors demonstrated that no additional phase-transfer catalyst (PTC) is needed when the PEG-bound electrophiles are coupled with appropriate aryl boronic acids. The polymer-bound substrates were coupled with 1.2 equivalents of the boronic acids in water under short-term microwave irradiation in sealed vessels in a domestic microwave oven (Scheme 7.62). Work-up involved precipitation of the polymer-bound biaryl from a suitable organic solvent with diethyl ether. Water and insoluble impurities need to be removed prior to precipitation in order to achieve high recoveries of the products. 

SYNTHESIS OF BIARYLS VIA PALLADIUM-CATALYZED CROSS COUPLING 2-NETHYL-4 -NITROBIPHENYL (l.l -Biphenyl, 2-methyl-4 -nitro-)... 

Scheme 16 shows parallel syntheses of cyclic and acyclic amide compounds. Fluorous benzaldehydes were first subjected to reductive amination reactions. The resulting amines were then reacted with isocyanates to form substituted hydantoin rings 14 or with benzoyl chlorides to form amides 15. Purified F-sulfonates were used for palladium-catalyzed cross-coupling reactions to form corresponding biaryl 16 [31] and arylsulfide 17 [32] products, respectively. 

The first observation concerning the preparation of biaryls was reported in 1981 [4]. Thus, the palladium-catalyzed cross-coupling reaction of phenylboronic acid with a number of haloarenes was found to proceed smoothly in the presence of base to selectively afford the corresponding biaryls in high yields (Eq. (1) and Table 1). 

Air-stable biaryl monophosphine ligands developed by Buchwald and co-workers have played a central role in the advancement of palladium-catalyzed cross-coupling reactions, including BHA chemistry the utility of appropriately configured ancillary ligands of this type in the selective monoarylation of ammonia has been examined. Following on preliminary experimentation that established the capability of the Pd2(dba)j/L3 catalyst system (dba=dibenzylideneacetone) to promote the monoarylation of ammonia at elevated temperature Tsvelikhovsky... 

Scheme 8 Palladium-catalyzed cross-coupling of (hetero)aryl bromides and chlorides with KOH employing XPhos-type biaryl monophosphines...

Scheme 2 Biaryl synthesis via palladium-catalyzed cross-coupling and direct arylation reactions...

The development of C-H activation for cross-coupling reactions has been advanced rapidly. Extensive efforts have been devoted to the mechanistic studies in this field to shed light on the mechanism. The use of oxygen or air as sole oxidant has been successfully realized in a palladium-catalyzed cross-coupling reaction involving C-H activation. We have the right to believe that palladium-catalyzed double C-H activation would be a good alternative for the synthesis of biaryls. With further improvements in catalyst turnover, selectivity, and oxidant, the method should ultimately be able to find industrial applications. 

Aryl chlorosilanes were found to undergo palladium-catalyzed cross coupling reaction with aryl chlorides in the presence of a fluoride salt giving unsymmetrical biaryls (see Scheme 36 [129]). A variety of functional groups (cyano, acetyl, fluoro, trifluoromethyl) are tolerated in this reaction. While the... 

One early example of microwave-assisted fluorous synthesis involved palladium-catalyzed Stifle couplings of fluorous tin reagents with aryl halides or triflates (Scheme 16.59) [90]. The desired biaryl products were isolated in good yields and purity after a three-phase extraction. Similar results were also achieved by use of so-called F-21 fluorous tags (CFl2CFl2CioF2i) on the tin reagent [91]. 

In 1993 Suzuki and colleagues described the palladium-catalyzed carbonylative coupling of aryl iodides with aryl boronic acids [13]. Various diarylketones were produced in high yields (Scheme 4.4). The choice of base and solvent was essential to obtain the desired ketones without biaryl by-products. The coupling of benzyl bromide was also described. In 1998 the group extended this methodology to aryl bromides and triflates [14]. In the case of aryl bromides, Nal or KI was required as an additive. The in situ transformation of aryl bromides to aryl iodides may be involved. 

Very recently, Tan and coworkers [20] reported the synthesis of unsymmetrical biaryls via palladium-catalyzed decarboxylative coupling between aryl carboxylic acids and phenylboronic acids. Under the optimized conditions, where the choice of solvent was found to be crucial for achieving a straightforward and simple coupling reaction, a variety of substituted benzoic acids were found to undergo decarboxylative coupling with several phenylboronic acids (Scheme 3.8). Despite poor substrate scope, this method could be useful and complementary to the Pd-catalyzed... 

The ready availability of arylboronates by an aromatic C-H borylation provides a synthetic link to the well-established palladium-catalyzed cross-coupling reactions, rhodium-catalyzed 1,4-addition to a,p-unsaturated carbonyl compounds, and other bond forming reactions using arylboronic esters (Scheme 2.12). Borylation of 1,3-dichlorobenzene with pinacolborane is followed directly by a cross-coupling reaction with methyl p-bromobenzoate for the synthesis of a biaryl product in 91% yield [60]. Pinacol esters of arylboronic acids react much slower than the free acids [62], but both derivatives achieve high isolated yields and comparable enantioselectivities (91% ee) in asymmetric 1,4-addition to N-benzyl crotonamides [63]. Borylation of arenes followed by oxidation of the C-B bond is synthetically equivalent to an aromatic C-H oxidation to phenols [64]. Oxidation of the resulting arylboronates with Oxone in a 1 1 acetone-water solution is completed within 10 min at room temperature. 

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