Palladium-catalyzed 2,3-diarylation

Buchwald and co-workers disclosed that the palladium-catalyzed diaryl ether formation can be performed with a 6/Pd-based system [152]. These reactions are accomplished using a mild base such as K3PO4, and with electron-poor aryl bromides, the reactions proceed in good to excellent yield, Eq. (194). 

Fugami K, Hagiwara S, Oda H, Kosugi M (1998) Novel palladium-catalyzed diarylation and dialkenylation reactions of norbornene derivatives. Synlett 477-478... 

A similar approach was used by Guo et al. for the palladium-catalyzed diarylation of 9-allyl-9J/-purines [47]. However, in their case, they relied on a chelation-assisted Pd-catalyzed highly regiose-lective diarylation reaction of olefins via a possible Pd(ll)/Pd(lV) catalyst cycle (Table 1.1). 

Palladium-catalyzed Diarylation. The title compound has been sho wn to efficiently undergo diarylation with chlorobenzene, employing a Pd(OAc)2/PCy3 catalyst and giving rise to compound 13. This transformation was achieved at relatively high temperatures in xylene, using an excess of base and aryl chloride (eq 15). 

The first palladium-catalyzed formation of aryl alkyl ethers in an intermolecular fashion occurred between activated aryl halides and alkoxides (Equation (28)), and the first formation of vinyl ethers occurred between activated vinyl halides and tin alkoxides (Equation (29)). Reactions of activated chloro- and bromoarenes with NaO-Z-Bu to form /-butyl aryl ethers occurred in the presence of palladium and DPPF as catalyst,107 while reactions of activated aryl halides with alcohols that could undergo /3-hydrogen elimination occurred in the presence of palladium and BINAP as catalyst.110 Reactions of NaO-/-Bu with unactivated aryl halides gave only modest yields of ether when catalyzed by aromatic bisphosphines.110 Similar chemistry occurred in the presence of nickel catalysts. In fact, nickel catalysts produced higher yields of silyl aryl ethers than palladium catalysts.108 The formation of diaryl ethers from activated aryl halides in the presence of palladium catalysts bearing DPPF or a CF3-subsituted DPPF was also reported 109... 

Carbon monoxide rapidly inserts into the carbon—zirconium bond of alkyl- and alkenyl-zirconocene chlorides at low temperature with retention of configuration at carbon to give acylzirconocene chlorides 17 (Scheme 3.5). Acylzirconocene chlorides have found utility in synthesis, as described elsewhere in this volume [17]. Lewis acid catalyzed additions to enones, aldehydes, and imines, yielding a-keto allylic alcohols, a-hydroxy ketones, and a-amino ketones, respectively [18], and palladium-catalyzed addition to alkyl/aryl halides and a,[5-ynones [19] are examples. The acyl complex 18 formed by the insertion of carbon monoxide into dialkyl, alkylaryl, or diaryl zirconocenes may rearrange to a r 2-ketone complex 19 either thermally (particularly when R1 = R2 = Ph) or on addition of a Lewis acid [5,20,21]. The rearrangement proceeds through the less stable... 

The palladium-catalyzed amination reaction with a monofunctional primary amine 167 effects i / -diarylation to afford the tertiary amine polymers 168. Hence, polycondensation of 167 with bifunctional arylene dihalides leads to 168 (Equation (81)). Polycondensation of a primary amine bearing an azobenzene moiety with dibromides in the presence of Pd2(dba)3 (2.5mol%)- Bu3P (P/Pd = 3 l) and NaO Bu at 100°G for 24h in toluene gives 168 in 81-93% yields, as reported by Kanbara. 

An nice example of the formation of a five membered ring in crosscoupling reaction is the hexamethyldistannane mediated ring closure of the dihalogenated diaryl ether shown in 3.1. The first step of the process is the palladium catalyzed exchange of one of the iodides to a trimethylstannyl moiety, followed by the closure of the five membered ring in Stille coupling. 

Palladium-catalyzed cross-coupling reactions of diaryliodonium tetrafluo-roborates have recently been employed for conversions of mercaptans to aryl-and diaryl sulfides, sodium arenesulfinates to diaryl sulfones, and dialkyl phosphites to aryl phosphonates (Scheme 43) [120-122]. 

Satoh, T. Kawamura, Y. Miura, M. Nomura, M. Palladium-catalyzed regioselective mono-and diarylation reactions of 2-phenylphenols and naphthols with aryl halides. Angew. Chem. Int. Ed. 1997, 36, 1740-1742. 

Palladium-catalyzed dimerization of arylselenocarboxamides 274 gave 3,5-diaryl-l,2,4-selenadiazoles 79 under mild reaction conditions (Scheme 37) <2002JOM274>. Treatment of arylselenocarboxamides 274 with aqueous... 

Two recent reports have detailed the palladium-catalyzed formation of diaryl-amines to prepare nucleosides of damaged DNA. Sigurdsson et al. reported the formation of a precursor to an interstrand cross-link by the reaction in Eq. (35) [158]. Lakshman reported the reaction of bromonucleosides with amines shown in Eq. (36) as a route to the DNA adducts of carcinogenic aminobiphenyls [159]. In this case, a number of reaction conditions were attempted and those using potassium phosphate and the P,N ligand 13 were effective for the transformation, albeit with high catalyst loads. 

Most recently, Wagaw, Yang, and Buchwald published a full account of the synthesis of indoles using the palladium-catalyzed amination process [185]. From the standpoint of catalysis, new results included improved turnover numbers and rates when Xantphos was used as ligand. Moreover, this ligand allowed diarylation of the hydrazone, including a one-pot sequential diarylation to provide mixed diaryl hydrazones. A procedure for the alkylation of N-aryl hydrazones was also reported. These procedures allow the formation of N-aryl and N-alkyl indoles after subjecting the products to Fischer conditions for indole synthesis. 

The palladium-catalyzed formation of diarylamines has been used in several contexts to form molecules of biological relevance. The ability to prepare haloarenes selectively by an ortfio-metalation-halogenation sequence allows the selective delivery of an amino group to a substituted aromatic structure. Snieckus has used directed metalation to form aryl halides that were subsequently allowed to react with anilines to form diarylamines (Eq. (34)) [209]. Frost and Mendonqa have reported an iterative strategy to prepare, by the palladium-catalyzed chemistry, amides and sulfonamides that may act as peptidomimetics. Diaryl-amine units were constructed using the DPPF-ligated palladium catalysts, and the products were then acylated or sulfonated with 4-bromobenzoyl or arylsulfonyl chlorides [210]. Le-miere has coupled primary arylamines with 4-chloro-3(2H)-pyridazinones to form compounds with possible analgesic and antiinflammatory properties. 

Aryl or diaryl substituted 3,4-(ethylenedioxy)thiophenes have been prepared by palladium-catalyzed direct C-H arylation of 3,4-(ethylenedioxy)thiophene itself with ary 1/he ternary 1 iodides/bromides <07TL539, 07T10363>, and direct coupling of... 

Bromo- and iodoimidazoles are useful intermediates for further functionalization. 4(5)-Aryl- I //-imidazoles 57 can be efficiently and selectively prepared by palladium-catalyzed Suzuki-Miyaura reaction of commercially available 4(5)-bromo-l//-imidazole 56 with arylboronic acids under phase-transfer conditions, which then underwent highly selective palladium-catalyzed and copper(I) iodide mediated direct C-2-arylation with a variety of aryl bromides and iodides under base-free and ligandless conditions to produce 2,4(5)-diaryl-l//-imidazoles 58 in modest to good yields <07JOC8543>. A new procedure for the synthesis of a series of substituted 2-phenylhistamines 60 utilizing a microwave-promoted Suzuki... 

This suggests that in the case that both intramolecular C- and 0-arylations are of geometrically equal possibility, the former preferentially takes place. The reaction of o-bromobenzaldehydes with dibenzylketones gives l,3-diaryl-2-naphthols that may be useful materials as bulky 0-ligands (Eq. 24) [62]. This cyclization involves palladium-catalyzed a-arylation and base-promoted dehy-drative condensation. Treatment of o-iodoanilines with ketones produces indole derivatives (Eq. 25) [63]. In this case, dehydrative condensation between the amino group and the carbonyl group occurs initially and the subsequent car-bopalladation (mechanism A) leads to the products. 

Olivera, R., SanMartin, R., Dominguez, E. A novel palladium-catalyzed intramolecular diaryl ether formation. Tetrahedron Lett. 2000,41, 4357 360. 

Aranyos, A., Old, D. W., Kiyomori, A., et al. (1999) Novel electron-rich bulky phosphine ligands facilitate the palladium-catalyzed preparation of diaryl ethers. Journal of the American Chemical Society, 121, 4369 4378. 

Nucleophilic displacement of chlorine, in a stepwise manner, from cyanuric chloride leads to triazines with heteroatom substituents (see Section 6.12.5.2.4) in symmetrical or unsymmetrical substitution patterns. New reactions for introduction of carbon nucleophiles are useful for the preparation of unsymmetrical 2,4,6-trisubstituted 1,3,5-triazines. The reaction of silyl enol ethers with cyanuric chloride replaces only one of the chlorine atoms and the remaining chlorines can be subjected to further nucleophilic substitution, but the ketone produced from the silyl enol ether reaction may need protection or transformation first. Palladium-catalyzed cross-coupling of 2-substituted 4,6-dichloro-l,3,5-triazine with phenylboronic acid gives 2,4-diaryl-6-substituted 1,3,5-triazines <93S33>. Cyanuric fluoride can be used in a similar manner to cyanuric chloride but has the added advantage of the reactions with aromatic amines, which react as carbon nucleophiles. New 2,4,6-trisubstituted 1,3,5-triazines are therefore available with aryl or heteroaryl and fluoro substituents (see Section 6.12.5.2.4). 

Transition metal catalyzed processes are useful tools for the synthesis of functionalized thiophenes. Thus for instance, a phosphine-free, palladium catalyzed coupling protocol for the synthesis of 2-arylbenzo[d]thiophenes from various 3-substituted benzo[6]thiophenes and aryl bromides or iodides has been reported <04T3221>. Likewise, 2,2 -bithiophenes have been 5,5 -diarylated directly with aryl bromides in the presence of Pd(OAc)2, bulky phosphine ligands and CS2CO3 <04T6757>. A series of electron-deficient and relatively electron-rich benzo[6]thienyl bromides have been shown to participate in palladium catalyzed amination reactions, as exemplified by the interesting conversion of 63 to the tetracyclic system 64 upon reaction with 2-aminopyridine 65 <04EJO3679>. 

Nova k et al. [75] synthesised 58 by palladium-catalyzed coupling of halogenated phenols (269) and acetylene (268). The resulting diaryl acetylene (270) underwent simultaneous cyclization upon removal of protecting groups as shown in Fig. (15). 

Sulfinate anions have been used as nucleophiles in palladium-catalyzed allylic alkylation [143]. More recently, both Cu- and Pd-catalyzed couplings of sulfinate anions with aryl halides have also been reported as a means to generate unsymmetrical diaryl sulfones, which are common motifs in bioactive molecules [38, 93, 144—148]. Similarly, Cu-catalyzed coupling of arylboronic acids with sulfinate anions has been reported [95,149,150]. Notably, Kantam and co-workers found that the use of ionic liquids permits Cu(OAc)2-catalyzed sulfone synthesis at ambient temperature and with convenient product separation and catalyst recyclability (17) [150]. 

Unusual palladium-catalyzed trichlorosilane-promoted deoxygenative dimerization of 1,4-epoxy-l,4-dihydroarenes was observed by Cheng, who prepared several diaryls in good to excellent yields. The mechanism is believed to involve a novel palladium-catalyzed... 

Palladium-catalyzed direct arylation of heteroaromatic Af-oxides using aryl triflates was reported to afford the corresponding 2-aryl heteroaromatic Af-oxides (Scheme 5) [21]. The reaction was carried out with a range of both azine Af-oxides and aryl triflates. The arylation can also be carried out as a sequence of reactions to yield various diarylated products. The regioselectivity and scope for the direct arylation of 3-substimted azine A -oxides have been investigated. The method can be apphed for the synthesis of compounds that exhibit antimalarial [22] and antimicrobial [23] activities. 

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