Arylation products

Photolysis of Cp2TiAr2 in benzene solution yields titanocene and a variety of aryl products derived both intra- and intermolecularly (293—297). Dimethyl titan ocene photolyzed in hydrocarbons yields methane, but the hydrogen is derived from the other methyl group and from the cyclopentadienyl rings, as demonstrated by deuteration. Photolysis in the presence of diphenylacetylene yields the dimeric titanocycle (28) and a titanomethylation product [65090-11-1]. 

Other limitations of the reaction are related to the regioselectivity of the aryl radical addition to double bond, which is mainly determined by steric and radical delocalization effects. Thus, methyl vinyl ketone gives the best results, and lower yields are observed when bulky substituents are present in the e-position of the alkene. However, the method represents complete positional selectivity because only the g-adduct radicals give reductive arylation products whereas the a-adduct radicals add to diazonium salts, because of the different nucleophilic character of the alkyl radical adduct. ... 

The reaction of an alicyclic enamine with benzyne intermediate yields simple arylation products and/or 1,2-cycloaddition products, depending upon the reaction conditions 102). This is illustrated by the reaction of l-(N-pyrrolidino)cyclohexene with benzyne (86) (obtained from fluoro-benzene and butyl lithium or o-bromofluorobenzene and lithium amalgam), which produces benzocyclobutene 87 102). 

The arylation of morpholinocyclohexene with 2- or 4-chloroquinoline N-oxide or 4-chloropyridine N-oxide and benzoyl chloride led to cyclohexanone a-substituted with the respective chloroquinolines or 4-chloropyridine (691). 2,4-Dinitrofluorobenzene reacted with 2-benzylidene-3-methylbenzothiazoline to give the enamine arylation product (672). 

The production of aryl radicals from peroxides normally provides a cleaner method of arylation than the methods based on the decomposition of azo and diazo compounds, and, in the case of benzenoid compounds, better yields of arylated products are obtained. The... 

The redCQon of l-nitrocyclohexene with triphenylbismuth thchloride in the presence of triethyldmine gives the deconjugated arylated product, as shovm in Eq 5 69 ... 

Since no relatively stable free radical is present (such as 26 in 14-17), most of the product arises from dimerization and disproportionation. The addition of a small amount of nitrobenzene increases the yield of arylation product because the nitrobenzene is converted to diphenyl nitroxide, which abstracts the hydrogen from 1 and reduces the extent of side reactions. ... 

The consistent observation of the arylated products with 92% ee confirms that the enantioselectivity of the asymmetric deprotonation was preserved during the transmetalation with ZnCl2 and retained during the Pd-catalyzed coupling. In fact, the Negishi coupling with 3-bromopyridine (entry 16) was performed at 60 °C, and still provided 26m in 92% ee, which constitutes a formal total synthesis of (R)-nicotine [27]. 

Having demonstrated a practical and reliable method to access 2-arylpyrrolidines in high enantioselectivity, we felt that a noteworthy extension of this methodology would lie in its application to bis-arylated products 27, providing a rapid and efficient approach to enantiopure C2-symmetric 2,5-diarylpyrrolidines, which have been identified as valuable chiral auxiliaries and chiral ligand manifolds [29]. Towards this end, substrate 26a was subjected to the standard arylation conditions, which produced 2,5-diphenyl-N-Boc-pyrrolidine 27 in a 96 4 diastereomeric ratio, and 57% isolated yield (s-BuIi/TMEDA produced 27 in lower d.r. (66 34) and yield (42%)), as depicted in Scheme 8.13. 

The reaction of 1-nitrocyclohexene with triphenylbismuth dichloride in the presence of triethylamine gives the deconjugated arylated product, as shown in Eq. 5.69.108... 

Microwave promoted, palladium-catalyzed, DPPP-controlled arylation of butyl vinyl ether with 4-tert-butylphenyl triflate afforded the branched arylation product and the corresponding methyl ketone, indicating the occurrence of selective internal a-arylation. Addition of water to the reaction mixture and microwave-heating for 2.8 min at 55 W smoothly produced the hydrolyzed product, 4-tert-butylacetophe-none, with an isolated yield of 77% (Eq. 11.2) [17]. 

In some cases multiple arylation products are obtained (Equation (144)). 

The palladium-catalyzed arylations of aromatic carbonyl compounds such as ketones,67,67a amides (Equation (60)),68 and aldehydes69 with aryl halides and triflates give the multiple arylation products similarly. 

In addition to palladium catalysts, Co(OAc)2 shows a catalytic activity for the arylation of heterocycles, including thiazole, oxazole, imidazole, benzothiazole, benzoxazole, and benzimidazole.78 As shown in Scheme 6, the catalytic system Co(OAc)2/9/Cs2C03 gives G5 phenylated thiazole, while the bimetallic system Co(OAc)2/CuI/9/Cs2C03 furnishes the G2 phenylated thiazole. The rhodium-catalyzed reaction of heterocycles such as benzimidazoles, benzoxazole, dihydroquinazoline, and oxazoline provides the arylation product with the aid of [RhCl(coe)]2/PCy3 catalyst.79 The intermediacy of an isolable A-heterocyle carbene complex is proposed. 

The Pd-catalyzed amination of / -rm-butylphenyl bromide with pyrrole in the presence of Pd(OAc)2, dppf and one equivalent of NaOr-Bu led to the Af-arylation product 88. A simplified version of the mechanism commences with the oxidative addition of p-te/t-butylphenyl bromide to Pd(0), giving rise to the palladium complex 89. Ligand exchange with pyrrole followed by deprotonation by the base (NaOr-Bu) results in amido complex 90. Reductive elimination of 90 then gives the amination product 88 with concomitant regeneration of Pd(0) catalyst. If the amine had a (3-hydride in amido complex 90, a (3-hydride elimination would be a competing pathway, although reductive elimination is faster than P-hydride elimination in most cases. 

Ohta s group investigated the heteroaryl Heck reaction of thiophenes and benzothiophenes with aryl halides [127] and chloropyrazines [128]. Addition of the electrophiles invariably took place at C(2) as exemplified by the formation of arylbenzothiophene 156 from the reaction of benzothiophene and p-bromobenzaldehyde [127]. As expected, the heteroaryl Heck reaction of 2-thienylnitrile, an activated thiophene, with iodobenzene afforded the arylation product 157 [129],... 

Miura s group carried out a heteroaryl Heck reaction of bromobenzene and 1-methylimidazole and isolated both mono-arylation (53%) and bis-arylation products [45], In accord with Ohta s observation, the first arylation took place at the electron-rich C(5) and the second arylation occurred at the more electron-poor C(2). 

The Stille reaction of 2-chloro-3,6-diisopropylpyrazine (7) and 2-chloro-3,6-diisopropylpyrazine 4-oxide (9) with tetra(p-methoxyphenyl)stannane (readily prepared in situ from the corresponding Grignard reagent and SnCU) led to the corresponding arylation products 8 and 10, respectively [9]. Additional Stille coupling reactions of chloropyrazines and their N-oxides have been carried out with tetraphenyltin [10] and aryl-, heteroaryl-, allyl- and alkylstannanes [11]. 

Along with some disubstituted furan 59, mono-arylation product 58 was isolated when 2-chloro-3,6-diethylpyrazine (57) and furan were refluxed in the presence of Pd(Ph3P)4 and KOAc. In the case of 2-chloro-3,6-dimethylpyrazine (23) and thiophene, monothienylpyrazine 60 was the sole product. When 2-chloro-3,6-diisobutylpyrazine was used as substrate, 9% of the disubstituted thiophene was detected. Analogous to the couplings with furan and thiophene, the heteroaryl... 

Although the heteroaryl Heck reactions of chloropyrazines with pyrrole itself were low-yielding for both mono- and bis-arylation products, better yields were obtained for N-phenylsulfonylpyrrole. Bulkier alkyl substituents on the pyrazine ring promoted the formation of C(3)-substituted pyrroles. The C(3)-substituted pyrrole 64 was the major product (62%) for the coupling of 1 and Al-phenylsulfonylpyrrole, while C(2)-substituted pyrrole 63- was a minor product (15%). 

Into a 500-ml five-necked flask fitted with a mechanical stirrer, a reflux condenser, and a thermocouple attached to a temperature controller is placed freshly activated granular zinc (4.3 g, 0.066 mol) and 25 ml dry acetonitrile. This mixture is stirred and heated to reflux (83°C) under nitrogen while the 2-bromotetrafluoroethoxy aryl product (amount corresponding to 0.021 mol equivalents of 2-bromotetrafluoroethoxy functionality) is dissolved in 21 ml of acetonitrile and added dropwise. The resulting mixture is stirred at 85°C for 6 h, then cooled and filtered. The filtrate is evaporated at 60°C under vacuum to remove the acetonitrile and the residue is purified by distributing the desired... 

Arylations of amines and nitrogen-containing heterocycles require the presence of a copper catalyst, usually 10% copper(ll) acetate. For example, the reaction of 4-MeC6H4Pb(OAc)3 with the benzimidazole 20 affords the arylation product 21 in 98% yield.39 40 Similarly, the arylation of the amino groups of heteroaromatic compounds 22 and 23 gives rise to the corresponding products 24a and 25 in good to excellent yields (Equations (7)-(9)).41 42... 

Insertion of aUcynes into aromatic C-H bonds has been achieved by iridium complexes. Shibata and coworkers found that the cationic complex [Ir(COD)2]BF4 catalyzes the hydroarylation of internal alkynes with aryl ketones in the presence of BINAP (24) [111]. The reaction selectively produces ort/to-substituted alkenated-aryl products. Styrene and norbomene were also found to undergo hydroarylation under similar condition. [Cp IrCl2]2 catalyzes aromatization of benzoic acid with two equivalents of internal alkyne to form naphthalene derivatives via decarboxylation in the presence of Ag2C03 as an oxidant (25) [112]. 

The reactions were run in toluene/acetone/water 4/4/1 in the presence of K2CO3 (strong bases had to be avoided due to the sensitivity of the starting compounds). A Pd-complex of l,r-bis(diphenylphosphino)ferrocene, [PdCl2(dppf)] proved to be the most efficient catalyst providing the arylated products in excellent yield (up to 98.6%) with complete retention of configuration i.e. with no loss of enantiopurity (Scheme 6.14). 

MeOC6H4, respectively. The titanium enolates were converted into silyl enol ethers 54 by treatment with chlorotrimethylsilane and lithium isopropoxide. Additionally, cyclic enones lb and Ic, and linear enones Id and le, are also good substrates for the asymmetric conjugate addition of phenyltitanium triisopropoxide, giving the corresponding arylation products with over 97% enantioselectivity. 

In terms of A -substitution, Hartwig reported improved conditions for the Pd(0) catalyzed N-arylation of indoles and pyrrole <99JOC5575>. It was found that when commercially available P(<-Bu)3 was employed as ligand and cesium carbonate as base, the reaction between indoles 95 and unhindered aryl bromides 96 or chlorides occurred under milder conditions than the Pd(OAc)2/DPPF system previously reported yielding the A/-arylated products 97. Alternatively, it has been found that pyrrole- and indole-2-carboxylic acid esters can be selectively 7V-arylated with phenylboronic acids in the presence of cupric acetate and either tiiethylamine or pyridine <99T12757>. 

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