Benzylic bonds

An important method for construction of functionalized 3-alkyl substituents involves introduction of a nucleophilic carbon synthon by displacement of an a-substituent. This corresponds to formation of a benzylic bond but the ability of the indole ring to act as an electron donor strongly influences the reaction pattern. Under many conditions displacement takes place by an elimination-addition sequence[l]. Substituents that are normally poor leaving groups, e.g. alkoxy or dialkylamino, exhibit a convenient level of reactivity. Conversely, the 3-(halomethyl)indoles are too reactive to be synthetically useful unless stabilized by a ring EW substituent. 3-(Dimethylaminomethyl)indoles (gramine derivatives) prepared by Mannich reactions or the derived quaternary salts are often the preferred starting material for the nucleophilic substitution reactions. 

Similarly, when both the Cp and arene ligands are permethylated, the reaction of 02 with the Fe1 complex leads to C-H activation of the more acidic benzyl bond [57]. When no benzylic hydrogen is present, superoxide reacts as a nucleophile and adds onto the benzene ligand of the FeCp(arene)+ cation to give a peroxocyclohexadienyl radical which couples with a Fe Cp(arene) radical. A symmetrical bridging peroxo complex [(Fe"Cp)2(r 5-C6H60)2] is obtained. The C-H activation reactions of the 19e Fe1 radicals BH can be summarized as follows... 

Primary 1,2-diamines can be obtained by hydrogenolysis of the benzylic N-auxiliary bond over Pd/C, e.g., the preparation of 249d. The cleavage is not selective in the presence of other benzylic bonds in the molecule, e.g., aryl substituents at Cl - C2. However, in the presence of methoxyphenyl or dimethoxyphenyl C substituents, the N substituents can be selectively removed, as exemplified by the preparation of the primary 1,2-diamine... 

It was found in the case of O-benzyl systems that palladium oxide is much more effective than palladium metal. No such effect was observed with the N-benzyl system.8 It is possible that the N-compounds can poison the electrophile metal ions, and the hydrogenolysis of the N-benzyl bond can take place only by the hydrogenolytic cleavage instead of the insertion mechanism. This is supported by the experimental finding that the product amine can inhibit the catalyst, and this can be minimized by buffering at a pH less than 4. 

In some cases the hydrogenolysis of the N-benzyl bond may be followed by an intramolecular N-acylation step (Scheme 4.69).310... 

Step 1 above requires that there be bonds in the coal that are weak enough to break in appropriate numbers at conversion temperatures and times. Table I displays some kinetic data for the cleavage of benzylic bonds in a series of increasingly aromatic compounds. In accord with expectation, an extension of the aromatic system increases the ease with which the benzylic bond is broken. 

THERMAL CLEAVAGE OF BENZYLIC BONDS IN AROMATIC SYSTEMS... 

The functionalization of benzylic bonds, leading to synthetically important boronates, has been described (Equation (31)). 

The high strain energy of [2.2]paracyclophane (see Section 2.1.) facilitates ring-opening of the molecule via cleavage of the benzyl-benzyl bonds. Pyrolysis at 400 °C affords p,p -dimethylbibenzyl (155) and p,p -di-methylstilbene 109h At 600 °C, p-xylylene (156) is formed it polymerizes spontaneously to the linear poly-p-xylylene (10) on condensation 110>. 

When the a-substituent is an ester and (SS)-DuPHOS is used one obtained the S-enantiomer of the amide. An electron releasing group (t-butyl) in this instance completely reverses the chirality [14] The explanation is that for electron-withdrawing a-substituents rhodium forms an a-alkyl bond, while for electron releasing a-substituents rhodium forms a (3-alkyl benzylic bond as shown in Figure 4.13 [15],... 

Molecular ions of phenylalkanes are comparatively stable due to the good charge stabilizing properties of the aromatic ring and thus, they normally give rise to intense peaks. Those molecular ions, possessing a benzylic bond preferably show... 

As already indicated in the preceding schemes, the resonance-stabilized benzyl ion, [CvHv]", initially formed by benzylic bond cleavage reversibly isomerizes to the tropylium and tolyl ion isomers. The isomerization of [CvHv]" ions has been the subject of numerous studies, [50] revealing the tropylium ion as the thermodynamically most stable isomer. [51,52]... 

Example Ethyl loss clearly predominates methyl loss in the El mass spectrum of 2-(l-methylpropyl)-phenol. It proceeds via benzylic bond cleavage, the products of which are detected as the base peak at m/z 121 and m/z 135 (3 %), respectively (Eig. 6.34a). The McLafferty rearrangement does not play a role, as the peak at m/z 122 (8.8 %) is completely due to the isotopic contribution to the peak at m/z 121. From the HR-El spectrum (Fig. 6.34b) the alternative pathway for the formation of a [M-29] peak, i.e., [M-CO-H]", can be excluded, because the measured accurate mass of this singlet peak indicates CgHgO". HR-MS data also reveal that the peak at m/z 107 corresponds to [M-CHs-CO]" and that the one at m/z 103 corresponds to [M-C2H5-H20]. Although perhaps unexpected, the loss of H2O from phenolic fragment ions is not unusual. 

Dibenzyl ditelluride exhibits the peculiar lability of the tellurium-benzyl bond already mentioned for the corresponding tellurides. By heating the solid at 120°C, or by exposure in solution to ordinary incandescent lighting or to a Hanovia lamp, a rapid decomposition into elementary tellurium and dibenzyl telluride occurs. ... 

Dibenzyl ditelluride on treatment with bromine nndergoes cleavage of the Te-benzyl bond, giving benzyl bromide and tellnrium tetrabromide. ... 

Cleavage of benzyl bonds is faster than cleavage of bonds to the aromatic ring because of overlap, in the transition-state, between the jt-system containing the unpaired electron and the stretching o-bond. Compare the reactivity of 4-... 

Phenylselenol, diphenylphosphine and diphenylarsine cleave Pt—Me bonds, but N-bromosuccinimide and 2-nitrobenzenesulfenyl chloride oxidize the methyl platinum(II) compounds to methyl platinum(IV) complexes (equations 208 and 209).573 m-Chloroperbenzoic acid cleaves the Pt—benzyl bond in PtCl(CHDPh)(PPh3)2 with retention of configuration at carbon.574... 

Hyperconjugation should raise the bond order between the ipso and benzylic carbons, and lower the bond order between the benzylic carbon and the silicon atom. As the ipso-benzylic bond length decreases, the 13C-13C coupling constant should increase, and as the benzylic carbon-silicon bond length increases, the 13C-29Si coupling constant should... 

They offer an even more surprising alternative in which reductive amination with benzylamine with reduction of the other ketone and cleavage of the A-benzyl bond followed by dehydration gives the simple amine 40. Now reaction with 1,3-dibromopropane gives 31, presumably again via 32 X = Br. 

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