Toluene meta-metalation

Toluene itself can be lithiated by w-BuLi-TMEDA at or above room temperature, and deprotonation occurs almost exclusively at the methyl group—about 10% ring metallation (mainly in the meta position) is observed with w-BuLi-TMEDA (Scheme 188) . At lower temperatures deprotonation is very slow , and the best conditions for achieving the metallation of toluene are the Lochmann-Schlosser superbases (see Section VI) °. 

Contrary to what is observed during tandem addition reactions to [Os]-toluene (vide supra), electrophilic additions to [Os]-bound ortho- and meta-xylenes result in regioselective attack at C6 (Table 3). A coordination isomer having the metal across C4-C5 (19) is the only isomer observed for both ortho- and meta-xylene. Electrophilic addition of HOTf (entry 1) or dime-thoxymethane (entries 2 and 3) at C6 generates the complexed allyl cation 20, which can be trapped with MMTP to form the complexed diene 21. Demetalation using AgOTf releases the free diene 22, which potentially possesses two adjacent quaternary centers (entry 3) [15]. 

When alkylbenzene derivatives are submitted to metallation, the metal may displace either a benzylic (a) or a ring hydrogen atom (preferably at the sterically unhindered meta or para positions). To avoid contamination by the ring-metallated derivative, a-deprotonation of toluene needs to be done with Schlosser s base18 191,192 while, for example, TMEDA-activated butyllithium gives rise to some contamination by ring-metallated products.193,194 Examples of mono- and dimetallation of alkylbenzenes are reported in Table 8. 

Activation of aromatic compounds by transition-metal complexes was initially studied with Cr(CO)3 complexes. Nucleophilic addition of 2-lithio-l,3-dithianes to arene-chromium(O) complexes 185 followed usually by iodine-promoted decomplexation affords the corresponding 2-arylated 1,3-dithianes 186. The reaction of //-(toluene)- and (anisole)tricarbonylchromium (185) with compound 161 gave mixtures (52 46 and 10 90, respectively) of ortho and meta substituted derivatives (186) (Scheme 54)244. The meta directing effect was also observed (mainly better than 95%) with amino and fluoro substituted complexes245. 

Novel reagents consisting of metallic nitrates impregnated on montmorillonite have been introduced in aromatic nitration. With clay-supported copper(II) nitrate in the presence of acetic anhydride it is possible to nitrate toluene quantitatively with a high para preference (79% para, 20% ortho, 1% meta). Also, good para selectivities have been found on nitration of some other aromatic hydrocarbons with copper(II) nitrate on clay. Halobenzenes are mononitrated with clay-supported copper(II) nitrate in the presence of acetic anhydride. Compared to other methods high para ortho ratios are obtained under these conditions. ... 

The formation of wetn-labeled toluene can be explained neither by direct 1-6 ring closure, nor by cyclic-type isomerization of n-heptane to 3-methylhexane followed by 1-6 ring closure of the latter (94). We suggest that the abnormal aromatization process responsible for the formation of meta-labeled toluene is initiated by a dicarbene as in the nonselective mechanism A (see Section IV, Scheme 47). Aromatization is not influenced by the dispersion of the platinum on the support (758), so that it may be assumed that aromatization involves a single metal atom. Isomerization of the dicarbenes (7) to the dicarbenes (8) via rt-adsorbed cyclopentanes, followed by isomerization to the suitable carbene-olefin species (9), would result in 1-6 ring closure and aromatization (Scheme 69). 

The principal monotrimethylsilyltoluene is the meta isomer. This agrees with the results of earlier experiments which find mainly m-lithio-toluene in the ring-lithiated byproducts in the synthesis of benzyllithium by lithiation of toluene with n-butyllithium-TMEDA (11, 12). On the basis of the current view that metalation of aromatic compounds proceeds... 

The reaction of rhodium acetate and P(C6F5)Ph2 is relatively slow. Mixtures of mono and bimetalated compounds are always obtained, even after heating for long periods in mixtures of toluene-acetic acid. The three possible isomers are detected in solution by P NMR spectroscopy. The isomer having a different configuration at each P atom (isomer IX, Scheme 3) is the dominant product (75%). The other two isomers are in fractions of 20%, (isomer X) and <5% (isomer VIII). The two major isomers, IX and X, have been characterized by X-ray crystallography. Rhodium(II) compounds with ort/jo-metalated diphosphines have been also re-ported. " The two P atoms coordinate two equatorial positions instead of having the axial-equatorial coordination observed for dinuclear platinum meta-lated compounds. ... 

When toluene was hydroxylated with the titanous ion-oxygen system in a constant volume of water, the yield of phenolic products depended on the amount of metal salt. The yield increased proportionately with the concentration of the metal ion. Under these conditions the phenolic isomer ratios changed continuously, the proportion of the meta isomer increasing with the metal ion concentration (Table i). 

The reaction of toluene with 1 could conceivably lead to four different trans-isomeric products by attack at the ortho, meta, para, or alpha positions. The carbanion chemistry of toluene would predict attack at the methyl group but, as in other transition metal arene activation studies (8,9,10), this is not found. The NMR spectrum of the toluene adducts displays two singlets attributable to trans-tolyl adducts in an intensity ratio of 1 1.6 in addition to resonances of cis-tolyl adducts. Selective mono-deuteration experiments show that the weaker downfield resonance is attributable to the para isomer while the stronger one is attributable to the meta isomer no ortho isomer is observed. If one corrects for statistical effects, the preference for para, meta, and ortho isomers is 1 0.8 0. We attribute this distribution of isomers primarily to... 

Unlike most of the other oxidative reactions developed in our group, the I(III)-mediated amination did not require the arene reagent to be used as a solvent. Near 1 1 ratios of the N-H and the C-H substrate could be used. Unfortunately, the metal-free amination provided intractable mixmres of products with monosubstituted and nonsymmetric arene substrates (Scheme 9). This problem was exemplified by the amination of toluene, which produced three regiomers in a 10 6 5 (ortho/meta/para) ratio. We demonstrated the application of the metal-free amination reaction with 18 substrates, but all nonsymmetric arenes produced complex mixtures of aminated products. " ... 

The Maleimide cure system is similar to the sulfur donor system in that it involves the decomposition of the sulfonyl chloride cure site. In this case, however, the Maleimide (meta-toluene-bis-maleimide, HVA-1 or meta-phenylene-bis-maleimide, HVA-2) rather than sulfur, is involved in the cross-links, and there is no evidence of a metal ionic bond. The reaction is usually initiated with an amine involving either an amine-catalyzed decomposition of the sulfonyl chloride group or a path of radical anions. The most recently developed initiators, which have been found to give a balanced combination of... 

The successful preparation of structural analogues of raised the hope that the chemistry of ammoxidation might also be reproduced in solution under mild laboratory conditions suitable for mechanistic studies. Thus we turned our attention to the critical C-N bond formation step to find out whether one can indeed produce ammoxidized product from a radical with a d imido metal center. For our studies diimido complexes (t-B iN)2M(OSiMe3)2 (M = Cr, Mo) [8,9] were selected as models for the postulated active sites in ammoxidation. Benzyl rather than allyl radicals were chosen for study since the products of allyl radical oxidation are not expected to be stable under our reaction conditions and because benzyl and allyl exhibit similar behavior in oxidation reactions [14]. Indeed, when a solution of (t-BuN)2M(OSiMe3)2 in toluene was heated at 100 C in the presence of benzoyl peroxide as a radical initiator, benzylidene-t-butylamine was obtained in up to 52% yield (Table I). The remaining organic products were C02> bibenzyl, and the expected isomeric distribution of (ortho meta para = 63 21 16) of methylbiphenyls. 

Studying these reactions in solution by quenching with electrophilic iodine revealed that while the weta-metalated product was the major product (73%), a small amount of ortho-metalation (6%) and para-metalation (21%) had also occurred [62]. The wefa-metalation of toluene can also be accomplished using the heteroleptic sodium magnesiate TMEDA-Na(TMP)(nBu)Mg(TMP) (Fig. 16) [63]. This base operates synergically via overall alkyl basicity to yield a discrete molecular framework containing a bridging molecule of toluene, metalated at the meta position [64]. 

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