Meta-selectivity

The meta-selectivity for toluene activation, observed for both systems, is very unusual (Fig. 5). Also remarkable is the switch in selectivity from aryl C-H activation to benzylic activation inp-xylene, just by changing the chelate ligand from the diimine equipped with trifluoromethyl substitutents in the meta-positions of the phenyl residue to the diimine bearing methyl substituents in the ortho-positions (Fig. 5). The authors suggested that the C-H bond activation is reversible and the isomeric a-methane complexes are in equilibrium prior to the substitution of... 

However, the frontier orbital picture based on the free arene does not account for nearly exclusive meta selectivity in addition to [(anisole)Cr(CO)3] LUMO for anisole shows essentially the same pattern as for toluene.98-100 With a strong resonance electron donor the traditional electronic picture (deactivation of the ortho and para positions) is sufficient to account for the observed meta selectivity. In this case the balance of charge control and orbital control is pushed toward charge control by strong polarization. The same argument applies to the aniline and fluotobenzene complexes. 

A delicate balance of charge and orbital effects can also account for the dependence of selectivity on anion type. The central assumption is that nucleophiles with a higher lying HOMO (softer) should give a better orbital energy match in the HOMO-LUMO interaction and increase the orbital control term. For the toluene ligand, this predicts strong ortho-meta selectivity for more reactive anions. 

Fig. 5.38. Electrophilic functionalization ortho to a C-bound DMG (on the left for comparison meta-selectivity of the analogous classic Ar-SE reaction).

One can compute, for example, the stabilizations AETS for the transition states of the para - and meta -selective cycloadditions, respectively, of acrylonitrile and isoprene according to Equation 15.2 with the data provided in Figure 15.26 (HOMO/LUMO gaps, LCAO coefficients at the centers that interact with each other). The result for the Diels-Alder reaction of Figure 15.25 is shown in Equations 15.4 and 15.5 ... 

This difference between the stabilization energies is a bit larger than in the case of the addition of acrylonitrile to isoprene (Equations 15.4 and 15.5). This agrees with the data in Figure 15.27, which show a para/meta -selectivity of 91 9 for the addition of 1,1-dicyanoethene to isoprene—i.e., somewhat higher than the 70 30 ratio of the addition involving acrylonitrile. 

In some cases, aniline or indole derivatives can be substituted meta to the nitrogen by lithiadon of the appropriate chromium tricarbonyl complexes. °" Examples are given in Scheme 3. One of the Cr—C=0 bonds eclipses the C—N bond, and therefore the other carbonyls eclipse the meta C—H bonds. Two suggestions have been offered for the meta selectivity (i) the butyllithium coordinates the chromium carbonyl oxygen and then removes the proximate proton (a kinetic effect) (ii) the eclipsed conformation produces a lower electron density at the meta position, which in turn renders the meta protons more acidic (a thermodynamic effect). ... 

Shape selectivity has also been demonstrated within FAU zeolites. For example, meta selectivity was observed for the NaY-mediated Friedel Crafts alkylation of benzyl chloride (BnCl) with itself. In addition to polymer inhibition, the FAU zeolite favored the formation of the banana-shaped l-(chloromethyl)-3-(phenyl-methyljbenzene (m-3) regioisomer (Equation (4)) 53... 

In HF-SbFs solution 4-aIkyl- and 2,6-dialkylphenols and their methyl ethers (anisoles) are converted to the O-protonated forms, which react with Br2 to afford m-bro-mophenol derivatives selectively (Scheme 14.35) [83, 84]. In HF-SbFs o- and p-bro-mophenols isomerize to m-bromophenol by a 1,2-Br shift in fhe protonated forms [85], When NaBr or KBr is used instead of Br2, the meta selectivity is reduced [86]. ElectrophiUc halogenation of arenes can also be performed with Ar SeCl [87]. 

The carbons of a pyridine are, in any case, electron-poor, particularly at the a-and 7-positions formation of a cr-complex between a pyridine and an electrophile is intrinsically disfavoured. The least disfavoured, i.e. best option, is attack at a j3-position - resonance contributors to the cation thus produced, do not include one with the particularly unfavourable sextet, positively-charged nitrogen situation (shown in parentheses for the a- and 7-intermediates). The situation has a direct counterpart in benzene chemistry where a consideration of possible intermediates for electrophilic substitution of nitrobenzene provides a rationalisation of the observed meta selectivity. 

One of the first eye-catching synthetic applications of arene-chromium chemistry was the synthesis of the sp/ro-sesquiterpenes ( )-acorenone and ( )-acorenone B (rac-7) disclosed by Semmelhack and Yamashita in 1980 [14]. These authors twice exploited the meta-selective nucleophile addition to anisole-Cr(CO)3 derivatives (Scheme 1). Starting from complex rac-1, such a reaction is first used for the regioselective introduction of an acyl sidechain to give 2 after oxidative workup. A few steps later, the nitrile rac-4 (obtained from rac-3 by complexation and separation of the diastereomeric products by preparative HPLC) is deprotonated to form the spiro addition product rac-5, from which the enone rac-6 is obtained after protonation and hydrolysis of the initially formed dienol ether. The final conversion of rac-6 into acorenone B (rac-7) efficiently proceeds over five steps and involves a diastereoselective hydrogenation of an exo-methylene group. 

The catalytic borylation offers unique selectivity when compared to traditional aromatic substitution reactions. Thus, mono- and 1,3-disubstituted (type 32) arenes react predominantly at meta-positions. This high meta-selectivity is a sterically controlled process. In the case of 1,3-difunctionized substrates borylation occurs exclusively at the 5-position even where functionalizations at the... 

Draw the mechanism for this reaction and you see the reason for the switch to meta selectivity. 

The reaction of methylbenzocyclobutene (292) with methylacetylene and of methoxybenzocyclobutane (293) with methylacetylene or ethoxyethylene gave the adducts (294—296) via the diene form of the benzocyclobutene, in the ratios indicated. The meta-selectivity found in the case of the first reaction may be the result of steric factors, but these cannot be important in the case of (293). The observed preference for meta-orientation in the additions is in accord with the predictions of frontier orbital theory for the reaction of a dienophile carrying an electron-donating substituent with dienes carrying electron-donating substituents at the 1- or 2-position. 

Three reviews have detailed progress in the formation of biaryl systems using metal-catalysed substitutions of carbon—hydrogen bonds. The preferential arylation at the para-position of phenol and aniline derivatives with diaryl iodonium salts has been achieved using copper catalysis. Under similar reaction conditions, a-arylacetamides are selectively arylated at the meta-position. A mechanistic study, including DFT calculations, suggests that the meta-selectivity in the copper-catalysed arylation of anilides derives from a Heck-like four-membered transition state involving a Cu(III)-phenyl species (47). 

Other representative couphng conditions include C-H arylations of benzene or naphthalene under Pd(0Ac)2/CF3C02Ag/CF3C02H catalysis by Lu [35], meta-selective C- H arylation by Gaunt [36], nickel-catalyzed C-H arylations (the reaction pathway likely involves radicals. See [ref. 131]) by Yamakawa [37], direct C-H arylation of naphthalene with aryliodonium salts by Sanford [38a], and polyfluoroarene C-H arylation in water by Zhang [39]. 

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