Arene regioselectivity

In calix[4]arenes, when the substituent at the lower rim is larger than ethyl, the conformational interconversion among these structures does not occur and it is possible to isolate the four stereoisomers/ Synthetic protocols for the selective functionalization of the OH groups of calix[4]arenes (regioselective alkylation) and for the selective synthesis of certain stereoisomers of tetraalkoxy calix[4]arenes stereoselective alkylation) have been developed." ... 

Some degree of regioselectivity can be imposed on l//-azepine formation if the arene has substituents of high steric demand.63 For example, the thermolysis of ethyl azidoformate in a tenfold molar excess of 1,4-di-fert-butylbenzene yields a 95 5 mixture of the di-zerr-butyl-l//-azcpincs 3 and 4, crystallization of which yields the pure 3,6-di-/er/-butyl isomer 3. 

An analogous regioselective effect of silver ions on an addition reaction of arene-diazonium ions was found by Ignasiak et al. (1975) with cyanide salts. Potassium cyanide yields diazocyanides (Ar— N2 — C = N see Sec. 6.6), i.e., C-coupling products, but with silver cyanide - albeit in low yield (7-9%) - diazoisocyanides (Ar—N2 — N = C) are formed (a better synthesis of diazoisocyanides is described in Sec. 6.4). 

Chromium carbene complexes having electron-rich arenes tethered to the car-bene oxygen or carbon underwent photodriven intramolecular Friedel-Crafts acylation in the presence of zinc chloride (Eqs. 32 and 33) [118]. The process was highly regioselective, undergoing acylation exclusively para to the activating group. 

When used with A-chloro-, A-bromo-, and A-iodosuccinimide, iron(III) chloride catalyzes the introduction of halogens into arenes. The reaction works well even with deactivated aromatic rings but in some cases the regioselective course is difficult to control (Scheme 39) [49]. 

Platinum mediated regioselective H-B addition of H-B(cat) to vinyl arenes and alkynes has been realised using the complexes 79 and 80 (Fig. 2.12). The reactions... 

An original mechanism involving the formation of an electrophilic Pd(ll) species was proposed to explain the inter-molecular /raor-arylpalladation process (Scheme 15), although more recent work has suggested a Pd(0) pathway. 68,6811 The non-directed carboxylation of arenes is mediated by Pd(ll), although regioselectivities would appear to be poor (Equations (69) and (70)). Very recent examples include Refs 69 and 69a. 

Gold-catalyzed direct C-H functionalizations enable the formation of polyalkylated arenes under mild conditions. In many cases, branched products are obtained. Two mechanisms are thought to operate with electron-rich arenes, an S si2-type mechanism via Au(lll) leads to the linear product. The branched product is obtained via a Friedel-Craft-type alkylation. A silver salt is often added and is believed to generate a more electrophilic Au(m) species. Often regioselectivities are poor and symmetric arenes are employed. Intramolecular variants as well as Michael additions are also known (Equations (72)-(74)).71,71a,71b... 

Remarkable carbon-boron bond-forming reactions are catalyzed by iridium complexes and proceed at room temperature with excellent regioselectivity, governed by steric factors. Heteroarenes are borylated in the 2-position and this reaction is generally tolerant of halide substituents on the arene (Equations (87) and (88)). 

Dinuclear palladium complexes catalyze m-hydroarylation of alkynes with arenes.56 The reaction of 3-hexyne with benzene in the presence of a dinulear palladium complex Pd2R2(M-OH)(//-dpfam) [dpfam = j/V,Ar -bis[2-(diphenyl-phosphino)phenyl]formamidinate, R=/>-Tol] and tri(/z-butyl)borane at 100 °C for 4h affords ( )-3-phenyl-3-hexene quantitatively (Equation (53)). The hydroarylation of 3-hexyne with monosubstituted benzenes ( )-3-aryl-3-hexenes with a 2 1 ratio of the meta- and ra -isomers. This regioselectivity is different from that of the hydroarylation of diphenylacetylene catalyzed by Rh4(GO)12.57... 

Palladium chemistry of heterocycles has its idiosyncrasies stemming from their different structural properties from the corresponding carbocyclic aryl compounds. Even activated chloroheterocycles are sufficiently reactive to undergo Pd-catalyzed reactions. As a consequence of a and y activation of heteroaryl halides, Pd-catalyzed chemistry may take place regioselectively at the activated positions, a phenomenon rarely seen in carbocyclic aryl halides. In addition, another salient peculiarity in palladium chemistry of heterocycles is the so-called heteroaryl Heck reaction . For instance, while intermolecular palladium-catalyzed arylations of carbocyclic arenes are rare, palladium-catalyzed arylations of azoles and many other heterocycles readily take place. Therefore, the principal aim of this book is to highlight important palladium-mediated reactions of heterocycles with emphasis on the unique characteristics of individual heterocycles. 

The anodic chlorination in some cases allows one to achieve better regioselec-tivities than chemical alternatives (p/o ratio of chlorotoluene in chlorination of toluene anodic 2.2, chemical alternative 0.5-1.0) [215]. Anodic oxidation of iodine in trimethyl orthoformate afforded a positive iodine species, which led to a more selective aromatic iodination than known methods ]216]. Aryliodination is achieved in good yield, when an aryhodide is oxidized in HOAc, 25% AC2O, 5% H2SO4 in the presence of an arene ]217, 218]. Alkyl nitroaromatic compounds, nitroaromatic ketones, and nitroanihnes are prepared in good yields and regioselectivity by addition of the corresponding nucleophile to a nitroarene and subsequent anodic oxidation of the a-complex (Table 13, number 11) ]219, 220]. 

Instead of stoichiometric amounts of Lewis acids (ZnCh, FeCh), small amounts of EGA (0.003-0.03 F) may catalyze acylation of electron-rich arenes when the electrophile precursor is used as solvent/co-solvent [40]. Yields in the range 22 to 95% are obtained, lowest when o-substitution has to take place as in 1,4-dimethoxybenzene. The regioselectivity is 75 to 98% [40]. 

Subsequent reports showed that a wide range of arene substrates could be borylated, with regioselectivity predominantly dictated by steric factors [77]. In the case of monosubstituted arenes, borylation generally occurs predominantly at the meta and para positions, with a near-statistical ratio while substitution at the ortho position is minor (Scheme 4). In the case of 1,3-disubstituted arenes, borylation occurs exclusively at 5-position. The selectivity was reversed in favor of the ortho position in the case of diethylbenzamide, presumably due to chelation [77]. 

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