Aryl intramolecular ortho-arylation

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 photostimulated intramolecular ortho-arylation reaction of bromoarenes linked to N-substituted tetrahydroisoquinolines in liquid ammonia was used for... 

N-Substituted amides can be prepared by direct attack of isocyanates on aromatic rings.The R group may be alkyl or aryl, but if the latter, dimers and trimers are also obtained. Isothiocyanates similarly give thioamides. The reaction has been carried out intramolecularly both with aralkyl isothiocyanates and acyl isothiocyanates.In the latter case, the product is easily hydrolyzable to a dicarboxylic acid this is a way of putting a carboxyl group on a ring ortho to one already there (34 is... 

The formation of these compounds has been rationalized according to Scheme 6. The reaction of Os (E )-CH=C 11 Ph C1 (C())( P Pr3)2 with n-BuLi involves replacement of the chloride anion by a butyl group to afford the intermediate Os (/i> CH=CHPh ( -Bu)(CO)(P Pr3)2, which by subsequent hydrogen (3 elimination gives OsH ( >CI I=CHPh (CO)( P Pr3)2. The intramolecular reductive elimination of styrene from this compound followed by the C—H activation of the o-aryl proton leads to the hydride-aryl species via the styrene-osmium(O) intermediate Os r 2-CH2=CHPh (CO)(P Pr3)2. In spite of the fact that the hydride-aryl complex is the only species detected in solution, the formation of OsH ( )-CH=CHPh L(CO)(P Pr3)2 and 0s ( )-CH=CHPh (K2-02CH)(C0)(P,Pr3)2 suggests that in solution the hydride-aryl complex is in equilibrium with undetectable concentrations of OsH ( )-CH=CHPh (CO)(P,Pr3)2. This implies that the olehn-osmium(O) intermediate is easily accessible and can give rise to activation reactions at both the olefinic and the ortho phenyl C—H bonds of the... 

Using the octafluorotolyl substituents, chains of doubly fluoride-bridged dimers are formed. Fluorine atoms in ortho-position of the aryl substituents contribute to tellurium coordination through intramolecular F- -Te contacts in the range of 320-330 pm.107... 

However, intramolecular O-alkylation can be performed under particular conditions leading to of annelation of a seven-membered heterocycle. Japanese researchers (170) prepared the corresponding seven-membered cyclic nitronates (50a-c) in good yields by the reaction of triethylamine with brominated aryl ketones (49a-c) containing the nitromethyl group in the ortho position. 

Rawal s group developed an intramolecular aryl Heck cyclization method to synthesize benzofurans, indoles, and benzopyrans [83], The rate of cyclization was significantly accelerated in the presence of bases, presumably because the phenolate anion formed under the reaction conditions was much more reactive as a soft nucleophile than phenol. In the presence of a catalytic amount of Herrmann s dimeric palladacyclic catalyst (101) [84], and 3 equivalents of CS2CO3 in DMA, vinyl iodide 100 was transformed into ortho and para benzofuran 102 and 103. In the mechanism proposed by Rawal, oxidative addition of phenolate 104 to Pd(0) is followed by nucleophilic attack of the ambident phenolate anion on o-palladium intermediate 105 to afford aryl-vinyl palladium species 106 after rearomatization of the presumed cyclohexadienone intermediate. Reductive elimination of palladium followed by isomerization of the exocyclic double bond furnishes 102. 

The Ir-MeDUPHOS catalyst also functioned efficiently in an intramolecular reaction, where triynes, which possessed ortho-substituted aryl groups on their termini, were transformed into ortho-diarylbenzene derivatives, which have adjacent two axial chiralities (Scheme 11.14) [22]. 

Diphenyl- -triazole is aminated by reaction with hydroxylamine-0-sulfonic acid. The I - and 2-aminotriazoles are formed in approximately equal amounts. Intramolecular amination of 1- and 2-aryltriazoles is achieved by generating a nitrene intermediate in the ortho position of the aryl substituent for example, in the thermolysis (Scheme 42) of the azide (17). ... 

The consecutive formation of o-hydroxybenzophenone (Figure 3) occurred by Fries transposition over phenylbenzoate. In the Fries reaction catalyzed by Lewis-type systems, aimed at the synthesis of hydroxyarylketones starting from aryl esters, the mechanism can be either (i) intermolecular, in which the benzoyl cation acylates phenylbenzoate with formation of benzoylphenylbenzoate, while the Ph-O-AfCL complex generates phenol (in this case, hydroxybenzophenone is a consecutive product of phenylbenzoate transformation), or (ii) intramolecular, in which phenylbenzoate directly transforms into hydroxybenzophenone, or (iii) again intermolecular, in which however the benzoyl cation acylates the Ph-O-AfCL complex, with formation of another complex which then decomposes to yield hydroxybenzophenone (mechanism of monomolecular deacylation-acylation). Mechanisms (i) and (iii) lead preferentially to the formation of p-hydroxybenzophenone (especially at low temperature), while mechanism (ii) to the ortho isomer. In the case of the Bronsted-type catalysis with zeolites, shape-selectivity effects may favor the formation of the para isomer with respect to the ortho one (11,12). 

With its (9r/ (9-(cu-phenylalkynyl) group, the iodoarene 156 in the presence of a palladium catalyst initiates the cascade process with an intramolecular carbopalladation this is followed by an intermolecular insertion, for example, into the double bond of the 3-azanorborn-5-en-l-one 157 and terminated by ortho-2XX,2Jz of the norbornyl-type cr-palladium intermediate on the previously terminal aryl group to yield the two regioisomeric hexacyclic systems 158 and 159 in a ratio of 1 1 (Scheme 39). ... 

Formation of l-aryl-l//-azepines is rare and occurs only with those arylnitrenes made sufficiently electrophilic by an electron-withdrawing, e.g. CN, N02 or CF3, ortho or para substituent. Even so, these docile nitrenes attack only electron-enriched arenes (e.g. mesity-lene or Af,Af-dimethylaniline) and are of minor synthetic importance (B-73MI51600). More reactive are 7r-deficient heteroarylnitrenes, and moderate yields (15-40%) of 1-heteroaryl-l//-azepines, e.g. (228 R=4,6-dimethoxy-l,3,5-triazin-2-yl), may be obtained by the photodecomposition of 2-azido-4,6-dimethoxy-l,3,5-triazine in a variety of aromatic substrates (81BCJ301). Interestingly, intramolecular insertion of arylnitrenes into arenes is more common and has been used for the synthesis of fused azepines, e.g. the azepinoindoles (229) from o-azidodiphenylmethanes (81JCS(P1)1132). 

Pyridylarenes undergo Cu(II)-catalysed diverse oxidative C-H functionalization reactions. The tolerance of alkene, alkoxy, and aldehyde functionality is a synthetically useful feature of this reaction. A radical-cation pathway (Scheme 4) has been postulated to explain the data from mechanistic studies. A single electron transfer (SET) from the aryl ring to the coordinated Cu(II) leading to the cation-radical intermediate is the rate-limiting step. The lack of reactivity of biphenyl led to the suggestion that the coordination of Cu(II) to the pyridine is necessary for the SET process. The observed ortho selectivity is explained by an intramolecular anion transfer from a nitrogen-bound Cu(I) complex.53... 

The use of hypervalent iodine reagents in carbon-carbon bond forming reactions is summarized with particular emphasis on applications in organic synthesis. The most important recent methods involve the radical decarboxylative alkylation of organic substrates with [bis(acyloxy)iodo]arenes, spirocyclization of para- and ortho-substituted phenols, the intramolecular oxidative coupling of phenol ethers, and the reactions of iodonium salts and ylides. A significant recent research activity is centered in the area of the transition metal-mediated coupling reactions of the alkenyl-, aryl-, and alkynyliodonium salts. 

The direct alkenylation of arylamines at the ortho position has been reported in reactions of o -chloroalkenylmagnesium chloride with N-lithioarylamines.22 Use of the CuI-L-proline catalyst system in DMSO has been found to be successful in promoting reactions of aryl iodides and bromides with activated methylene compounds, such as ethyl acetoacetate and diethyl malonate.23 The same catalyst in dioxane has been used in intramolecular cyclization of ene-carbamates leading to indoles or pyrrolo[2,3-cjpyridines.24... 

Growing attention is directed to intramolecular reactions involving alkyls attached to position 5 of the tetrazole ring. The synthesis of 4,5-dihydrotetrazolo[l,5- ]quinoxalines 347 from 5-substituted tetrazoles 346 via the intramolecular. KNAr substitution of the halogen in the ortho-position of the iV1-aryl substituent is an example of such a reaction (Equation 64) <2006TL2041>. 

The synthesis of selectively substituted benzoxepines from ortho-substituted aryl iodides and bromoenoates has been achieved by Lautens and coworkers by palladacycle alkylation followed by an intramolecular Heck reaction under the modified conditions reported in Eq. (8) for synthesis of l-(l-ethoxycarbonylmethy-lene)-9-methyl-4,5-dihydro-3-benzoxepine [8]. In the second example (Eq. 9) the palladium-bonded biphenylyl inserts diphenylacetylene to form 1,5-di-i-propyl-9,10-diphenylphenanthrene[9]. In the last case the synthesis of 4-methyl-5H-phenanthridin-6-one is achieved by palladium-catalyzed sequential C-C and C-N bond formation starting from o-iodotoluene and o-bromobenzamide [10]. 

Undesirable photochemical reactions occur with many aryl azides that have ortho substituents, which should be avoided. Intramolecular reaction of the nitrene results in wastage of the photogenerated intermediates, e.g. Fig. 3.4. 

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