Cu-catalyzed and promoted arylations

N-Arylaminophthalimides, hydrazines, hydrazones, and N-H containing heterocycles are N-arylated by combined use of Ar3Bi and Cu(OAc)2 (Scheme 14.134) [281] in which Cu(OAc)2 oxidizes Ar.l i to Ar jl i(OAc)2 and catalyzes the arylation via transmetalation (Section 14.3.4.2). The Cu(OAc)2-promoted N-arylation of amides, sulfonamides, ureas, carbamates, and anilines with ArsBi proceeds efficiently in the presence of EtsN or pyridine (Scheme 14.135) [282]. N-Arylation occurs selectively on the primary amino group of aminobenzanilides (Scheme 14.136) [283]. A variety of amines are N-alkylated in moderate yields by use of alkylbismuthanes assisted by Cu(OAc)2 [284]. 

Aryl and alkyl-substituted diynes and tetraynes have been synthesized in good yields (82-99%) by TBAF-promoted desily-lation and Cu-catalyzed oxidative dimerization of triisopropylsi-lyl (TlPS)-protected acetylenes (eq 38). Copper acetate was used as oxidant in this reaction. Aryl- and alkenyl alkynes were made under similar conditions (eq 39). Pd/C with TBAF was used in ligand- and copper-free, one-pot, domino Halex-Sono-gashira reactions. Similarly, TBAF promoted the synthesis of 2-substituted indoles by a tandem Sonogashira/cyclization reaction of 2-iodoanilines and terminal alkynes. ... 

Arylation of active methylene compounds has been carried out using Cu salts as promoters under severe conditions [2], Recently it was discovered that the reaction can be carried out much more smoothly using Pd catalysts. The first Pd-catalyzed intermolecular arylation of cyanoacetate and malononitrile with aryl iodides was carried out by Takahashi using PPhs as a ligand, and was applied to a simple synthesis of tetracyanoquinodimethane (2) by the reaction of p-diiodobenzene with malononitrile [3], The intramolecular arylation of malonates and -diketones with aryl iodides proceeds smoothly. Presence of a cyano group seemed to be important [4,5], The arylation has been successfully extended to halides of heterocycles, such as pyridine, quinoline and isoquinoline. The reaction of bromoxazole 3 with sulfone 4 is an example [6]. 

In 2009, Lee and Hoveyda developed a Cu-catalyzed method for enantioselective conjugate additions of aryl and alkenyl groups to cyclic enones (Scheme 3.52) [79]. Reactions were promoted by chiral monodentate, non-C2-symmetric NHC-Cu complexes generated in situ from carbene salts such as 91. The desired p-aryl- or p-vinylcycloalkanones were obtained in up to 97 and 92% ee, respectively. Remarkably, the easily accessible aryl- or alkenylsilane reagents were used as nucleophiles and thus did not require the use of air- and moisture-sensitive organometallics. 

Hiyama and co-workers have reported that the Mizoroki-Heck-type reaction of aryl- and alkenylsilanols is efficiently promoted by a Pd(OAc)2/Cu(OAc)2/LiOAc system (Equation (9)).50 50a in contrast, a dicationic Pd(ll) complex prepared in situ from Pd(dba)2, a diphosphine (dppe or dppben), and Cu(BF4)2 catalyzes 1,4-addition of aryltrialkoxysilanes to a-enones and a-enals in aqueous media (Equation (10)).51 The Pd-catalyzed 1,4-addition of the arylsilanes can be achieved also by using excess amounts of TBAF 3H20, SbCl3, and acetic acid.52... 

The Cj p3-O bond of 2-tert-butoxy-furan and -thiophene is cleaved catalytically by BiCl3 or Bi(OTf)3 to produce 2(5H)-furanone and -thiophenone, respectively [254]. The selective hydrolysis of aryl esters is catalyzed by bismufh(III) mandelate in DMSO [255]. In the presence of 50 mol% Bi(NO3)3-5H2O, 10 mol% Cu(OAc)2, and Montmorillonite KIO ketoximes undergo facile deoximation in acetone-H2O [256]. Under microwave irradiation the BiCls-promoted hydrolytic cleavage of the C=N bond of dimethylhydrazines, tosylhydrazines, semicarbazones, and oximes proceeds in wet THF (Scheme 14.120) [257-259]. 

Due to poor reactivity, aryl amines normally require higher reaction temperatures than aliphatic amines to ensure good conversion. In early studies, phenathroline and its Cu(I)-complex were used in the arylation of aryl amine [10, 11], but they were only applicable to the synthesis of triarylamine from secondary aryl amines. L-Proline (LI) promoted Cul-catalyzed arylation of primary aryl amines took place at 90°C (Table 9.1, entry 1) [3]. However, only electron-rich anilines gave complete conversion, while electron-deficient anilines provided low yields. Fu found that this drawback could be overcome by heating at 110°C and using pipecolinic acid (L5) as a ligand (entry 2) [12]. Similar studies were reported by Liu and coworkers in which DMEDA (Lll) was found to be a better ligand (entry 3) [13], Recently, Buchwald reported that pyrrole-2-carboxylic acid (L6) [14] is an efficient promoter for the synthesis of diarylamines (entry 4) (Table 9.3). 

Very recently, Jun et al. [179] have described the synthesis of isoquinoUnes 181 and pyridines 182 by the [Cp RhCy2-catalyzed Al-annulation reaction between aryl or a,p-unsaturated ketones 179-180, alkynes 178, and NH OAc, employing stoichiometric amounts of Cu(OAc)j as the oxidant and microwave irradiation. The reaction is successful with a wide family of arylketones 179 and enones 180 to afford the desired isoquinolines 181 and pyridines 182 in good to excellent yields (Scheme 3.69). A four-component reaction could be developed by in situ generation of enones by aldol reaction between an enolizable ketone and formaldehyde, affording the desired products in moderate yields. The proposed mechanism involves the Rh" -promoted consecutive N—H and p-C—H bond activation of imine XXXVII, generated from ketone/enone and NH, ... 

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