Ortho arylation

The ortho-arylation of 2-arylpyridines with aryltin reagents is mediated by Wilkinson s catalyst. This cross-coupling procedure occurs at high temperatures and consequently, the prevention of double phenylation represents a major hurdle, which is often achieved by adding a methyl group to either the pyridine or aryl group (Equations (125) and (126)).1... 

Aromatic imines can be ortho-arylated and alkenylated using ruthenium catalysis (Equation (129)).1... 

In addition to aryl halides and triflates, organometallic reagents can be utilized for the catalytic arylation reaction. The rhodium-catalyzed arylation of arylpyridines proceeds with the use of tetraarylstannanes (Equation (67)).83 The ruthenium-catalyzed reaction of aromatic ketones with arylboronates affords the ortho-arylated aromatic ketones (Equation (68)).84... 

In spite of the attention focused on these bulky aryl substituents, especially in main-group chemistry, aryl ligands in which crowding is caused by the presence of ortho-aryl substituents formerly received little attention. In contrast, related terphenyl-substituted phenolate derivatives (e.g., -OC6H3-2,6-Ph2) of the early transition metals have been studied for many years, and zinc terphenolate derivatives have attracted attention (vide infra). A small number of similar aryl thiolate derivatives of transition metals (e.g., Mo, Fe, and Rh) have been characterized and published (vide infra). In addition, the related ligand -C6H2-2,4,6-Ph3 (Triph) had been employed as a ring substituent in bulky porphyrins.24... 

The process shown in the right half of Scheme 13 represents the selective ortho arylation of an iminopyridinium ylide, directed by the CO group, which affords adequate precursors of natural products [113, 114]. 

In the introduction of exp. 3 it is mentioned that lithiated acetylenes react very slowly at 70 C with dimethylfonnamide. However, lithiated benzene derivatives in most cases add very quicldy to DMF at these low temperatures. This difference in basicity may explain the specific reaction of the ortho-aryl negative center in dilithiated phenylacetylene with dimethyl-formamide. 

The crystal structure of the lithium complex [Pr 2N(Ph)COLi(p-tmp)(p-Bu )ZnBu shows that the amide solvates the lithium ion through oxygen with zincation of the aryl occurring via interaction of the ortho aryl hydrogen Bu or tmp group." The crystal... 

Alkyl aryl ketones are known to be arylated at the a-position of the alkyl groups, via the corresponding enolates, by treatment with aryl halides in the presence of palladium catalysts [4, 9]. The ortho arylation of alkyl aryl ketones is also possible. For example, in the reaction of benzyl phenyl ketones with bromobenzenes, the arylation first occurs at the benzylic position the ortho positions are then arylated via C-H bond cleavage (Eq. 8) [15]. The ortho arylation is believed to occur after coordination of the enol oxygen to ArPd(II), which is followed by ortho palladation as in the reaction of 2-phenylphenols shown in Scheme 2. 

Benzanilides also undergo ortho arylation (Eqs. 9 and 10) [16]. For these reactions, aryl triflates as arylation reagents are more effective than aryl bromides. The reaction is also believed to proceed via coordination of amide anion to ArPd(II), because no reaction occurs with secondary amides. 

Benzylidene anilines formed from benzaldehydes and anilines have been found to undergo ortho arylation effectively when a ruthenium catalyst such as [RuC12(/ 6-C6H6)]2 is used in the presence of K2C03 as base (Eqs. 11 and 12) [17]. A polar solvent such as NMP is used. In this reaction the substrates have no acidic hydrogen and thus ortho metalation seems to occur via coordination of the neutral nitrogen to the metal center, as in the reaction of phosphinite (Scheme 3). Similarly, 2-phenylpyridine [18] (Eq. 13) and 2-phenyl-lH-imidazole (Eq. 14) [19] are arylated. 

Scheme 4. Rhodium-catalyzed ortho-arylation of t-butyl phenyl ketone with 5,5-dimethyl-2-phenyl-[l, 3,2]dioxaborinane.

The aporphine skeleton 21 can be synthesized through the SrnI mechanism by exploiting the bidentate behavior of phenoxide ions that allows one to obtain the ortho-arylation in good yields, as shown in Scheme 10.43 [59]. Tetrahydroisoquinoline precursors that contained nitrogen-based EWGs (i.e., amides, sulfonamides,... 

The intramolecular ortho-arylation of aryl amide ions with aryl iodides has been recently applied to the synthesis of phenanthridines 25 in excellent yields (Scheme 10.49) [66], By applying the same procedure, N-(2-iodobenzyl) naphthalene-amine and N-(2-chlorobenzyl) naphthalen-1-amine yield benzo[a]- andbenzo[c] phenanthridines in 98% and 84% yields, respectively [66]. 

Barolo, S.M., Teng, X., Cuny, G.D. and Rossi, R.A. (2006) Syntheses of aporphine and homoaporphine alkaloids by intramolecular ortho-arylation of phenols with aryl halides via SRn1 reactions in liquid ammonia. Journal of Organic Chemistry, 71, 8493—8499. 

The ortho-arylation of aromatic aldehydes in the presence of a combination of Pd(II)/saturated imidazolium salt has also been reported [174]. Remarkably, the formation of the mono- or bi-orf/zo-substituted product could be easily controlled depending on the nature of the aromatic halide employed (Scheme 23). Both electron-donating and electron-withdrawing substituents were well tolerated by the catalytic system and heteroaromatic aldehydes could also be coupled. 

The rationale offered for these observations is based on the hypothesis that steric repulsion between the backbone phenyl groups and the ortho-aryl substituents stabilizes their mutual anti-conformation, which in turn permits... 

When DABCO is replaced by brucine, enantioselective ortho-arylation of the aniline takes place at low temperature (—78 to —40°C) to afford the chiral biaryl with moderately good enantioselectivity (Equation (51)).68... 

The first enantioselective total synthesis of the 7,3 -linked naphthylisoquinoline alkaloid (-)-ancistrocladidine was accomplished by J.C. Morris and co-workers. The key steps of the synthesis were the Pinhey-Barton ortho-arylation and the Bischier-Napieralski cyclization. The natural product was isolated from the 1 1 mixture of atropisomers by recrystallization from toluene/petroleum ether. 

A mixture of mesitol, p-methoxyphenyllead triacetate, and pyridine in equimolar quantities in chloroform gives an almost quantitative yield of fhe 6-arylcyclohexa-2,4-dienone and the 4-arylcyclohexa-2,5-dienone in a ratio of 4 1 (Scheme 13.19) [45], There is a marked preference for ortho arylation. 

Phenol ortho-Aryl dienone (41) para-Ary dienone (42) Anisole Other products, (%)... 

While using o-bromophenol as the ort/w-arylating agent in the above sequence, Catellani found the product to be a 67/-dibenzopyran, the product of an ortho-arylation/Mizoroki-Heck coupling followed by an oxy-Michael addition of the phenol to the electron-deficient alkene. This was later developed into an efficient method for the synthesis of a variety of 6//-dibenzopyrans (Scheme 21) [56, 57], and is one of the most modular and effective methods to construct this interesting heterocyclic framework. 

Scheme 31 Aryl cyanides synthesized via ortho-arylation/Cyanation reaction...

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