Regioselective diarylation

A mild and efficient Pd(II)-catalyzed oxidative regioselective diarylating carbocyclization of dienynes was developed by using arylboronic acids with stereoselective formation of tetrahydrofurans and tetrahydropyrans (13CEJ6571). 

A drawback of the Heck-type reaction is that it is not strictly regioselective [119]. Depending on the substituents >1% of 1,1-diarylation is observed. Soluble 2,5-dialkoxy-PPVs 63 or 2-phenyl-PPV PPPV 93, without 1,1-diarylated moieties, were synthesized by Heitz et al. in a Suzuki-type cross coupling of substituted 1,4-phenylenediboronic acids and fran5-l,2-dibromoethylene, catalyzed by Pd(0) compounds [120]. However, about 3% of biaryl defect structures are observed in the coupling products (M up to 12,000), resulting from homocoupling of boronic acid functions. 

The following syntheses all proceeded regioselectively 4,6-diaryl-3,4-dihydropyrimidine-2-thiones with 3-bromopropionic acid in a Ac20/AcOH system <2001MI407, 2000IJH49>, or with acrylonitrile in pyridine followed by hydrolysis <1996IJB915> resulted 6,8-diaryl-2,3-dihydro+//,6//-pyrirnido[2,l+][l,3]thiazin-4-ones in good yield 4-phenyl-5-carbethoxy-3,4-dihydropyrimidine-2-thiones with benzylidenemalonitrile in a NaOAc/AcOH system... 

Two groups simultaneously found that trimethylsilyl cyanide reacts with disubstituted acetylenes in the presence of a Pd catalyst to form silylated 2-amino-5-cyanopyrroles 194 or 195 [133, 134], These reactions are run neat and a variety of Pd species are successful in this transformation [133]. In the case of unsymmetrical diaryl acetylenes, the reaction is not regioselective [134],... 

In 2002, Kiindig et al. [23, 24] developed catalytic DCR between diaryl nitrones and a,(3-unsaturated aldehydes in the presence of Binop-F iron and ruthenium complexes as chiral Lewis-acid catalysts (Scheme 6). The corresponding cycloadducts were obtained in good yields with complete endo selectivity and up to 94% ee. The isoxazolidine products were obtained as a mixture of regioi-somers in molar ratios varying from 96 4 to 15 85. Experimental and computational data show that the regioselectivity correlates directly with the electronic properties of the nitrone. 

Hydrosilylation of monosubstituted and. em-disubstituted olefins (Reactions 5.3 and 5.4) are efficient processes and have been shown to occur with high regioselectivity (awti-Markovnikov) in the case of both electron-rich and electron-poor olefins [25]. For cis or trans disubstituted double bonds, hydrosilylation is still an efficient process, although it requires slightly longer reaction times and an activating substituent (Reaction 5.5) [25]. Any hydrosilylation product has been observed with 1,2-dialkyl-and 1,2-diaryl-substituted olefins, due to the predominant reversible addition of (TMS)3Si radical to the double bond [19]. 

The 1,3-dipolar cycloaddition of diarylnitrile imines 98, generated in situ from arylhydrazones with chloramine T or from a-chlorobenzylidenephenylhydrazine with triethylamine, to some 5-substituted 2-methylpyridazin-3(2//)-ones 88, 99-101 has been shown to afford l,3-diaryl-l,5-dihydro-4//-pyrazolo[3,4- ]pyridazin-4-ones 102 regioselectively (Scheme 21) <2000JMT(528)13>. 

The cycloaddition reactions of the unsymmetrical a-diazo-/3-diketone, 2-diazo-l-phenyl-l,3-butanedione 330, with diaryl imines 331 took place with high regioselectivity, affording exclusively the 6-methyl-5-phenyl-substituted 477-l,3-oxazin-4-ones 332 via the acetylphenylketene, generated by the thermal Wolff rearrangement of 330 (Equation 32) <2002HAC165>. 

Moreover, when the reaction was performed with a multifunctional substrate, such as 4-acetyl-benzophenone (85), the yield in diaryl methanol was 1.3 times higher than that derived from the reduction of the acetyl group. On the other hand, when the non-imprinted polymer was used, the regioselectivity was reversed, with the yield of reduced acetyl being 1.7 times higher than the diarylmethanol. 

Treatment of arylidenepyruvic acids 236 with 5-amino-3-arylpyrazoles 222 (R is Ar, Ri is H) in most cases was not regioselective and yielded mixtures of several regioisomers and products of their heteroaromatization 2,7-diaryl-4,7-dihydropyrazolo[l,5-tf]pyrimidine-5-carboxylic acids 246 (main product), 3,4-diaryl-4,7-dihydropyrazolo[3,4-Z ]pyridine-6-carboxylic acids 247 and their heteroaromatized derivatives 248 (Scheme 3.68). 

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. 

The diaryl substituted systems (139) have been shown to undergo regioselective cleavage of the cyclopropene o-bond bearing the more electron donating substituent under direct photolysis 116). 

A rational extension of ortho-tolyl benzamide metalation [68], part of the broadly encompassing lateral metalation protocol [69] that can be DoM-connected, is the DreM equivalent, 154 —> 155 (Scheme 41), which provides a general regioselective route to 9-phenanthrols (156, 157, 158) [70] and may be extended to diaryl nitriles, hydroxylamine ethers, and hy-drazones 160, which provide the corresponding 9-amino derivatives 161 of similar generality 162-165 (Scheme 42), as may also be applied in natural product synthesis [71]. Further opportunities for DoM-cross-coupling and reduction/oxidation chemistry (159) have also been demonstrated [70a]. 

Biphenyl-2-ols undergo not only monoarylation but also diarylation on treatment with iodobenzenes to give the corresponding products coupled regioselectively at the 2 -positions (Eq. 56) [46,50]. Thus, sterically crowded 1,2,3-triphenylbenzene derivatives are obtained by single treatment. While 4 -substituted biphenyl-2-ols are also diarylated, 3 -substituted ones give only monoarylated products due to steric reasons (Eq. 57). The reaction of biphenyl-2-ols seems to involve coordina-... 

The addition of ZnBr2 to the tandem 1,3-azaprotio cyclotransfer-cycloaddition of a ketoxime with divinyl ketone results in rate enhancement and the exclusive formation of l-aza-7-oxabicyclo[3.2.1]octan-3-ones7 The 1,3-dipolar cycloaddition of 1-aza-l-cyclooctene 1-oxide with alkenes produces the corresponding isoxazolidines in high yields with a minimum of polymeric material. The cycloaddition of thiophene-2-carhaldehyde oxime with acetonitrile and methyl acrylate produces the 1,3-dipolar adduct, suhstituted isoxazolidines, and not the previously reported 4 - - 2-adducts. Density functional theory and semi-empirical methods have been used to investigate the 3 + 2-cycloaddition of azoxides with alkenes to produce 1,2,3-oxadiazolidines. The 3 -h 2-cycloaddition of a-nitrosostyrenes (62) with 1,3-diazabuta-1,3-dienes (63) and imines produces functionalized cyclic nitrones (64) regioselectively (Scheme 22). The first imequivocal 1,3-dipolar cycloaddition of sulfines involves the reaction of 2,2,4,4-tetramethyl-3-thioxocyclobutanone S-oxide with diaryl thioketones to produce... 

With mixed diaryl or alkyl aryl anhydrides, the regioselectivity of attack by the tetracarbonylferrate is, not surprisingly, too poor to be synthetically useful. However, the reagent can be usefully applied to the mixed carboxylic alkylcarbonic anhydrides (23), giving aldehydes after treatment of the intermediate acylferrates with acetic acid (equation 3). The substrates (23) are readily available from carboxylic acids by treatment with ethylchloroformate and triethylamine. Unfortunately the quoted g.c. yields are variable e.g. benzaldehyde, 41% p-tolualdehyde, 76% nonanal, 51%), suggesting that further development may be required. 

Condensation of 7-keto-ester hydrazones 475 with the Vilsmeier reagent yielded a general synthesis of l,3-diaryl-4-pyrazoleacetic acid esters 476 (Equation 95) <2005JHC131>. Regioselective addition of lithiated /3-hydrazono-phosphino oxides 477 to isocyanates afforded functionalized hydrazonoamides 478, which were then cyclized to 5-aminopyrazoles 479 with phosphorus oxychloride in the presence of triethylamine (Scheme 56) <1996T4123>. 

In DMF containing lithium perchlorate, reduction of o -bromopropiophenone at mercury gives l,4-diphenyl-2,3-dimethylbutan-l,4-dione in 65% yield [236]. However, electrolysis of a-bromopropiophenone in the presence of benzoyl chloride affords only l,3-diphenyl-2-methylpropan-l,3-dione. Other studies involving reduction of phenacyl bromides include the electrosynthesis of 4-aryl-2-methylfurans [237] and the regioselective synthesis of enol carbonates [238] semicarbazones of phenacyl bromide can be converted into 3,7-diaryl-2/7-imidazo[2,l-Z>][l,3,4]oxadiazines [239]. Reduction of 1,2-dibenzoyl-chloroethane at mercury in DMF containing lithium perchlorate affords mixtures of phenyl tribenzoyl cyclopentanols and diphenyl dibenzoyl butanediones [240]. 

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