Reactions at a Benzylic Position

Normal alkenes—which are particularly not electron-rich—are oxidized at the allylic position by PCC, resulting in the formation of enones.264 Aromatic compounds suffer a similar reaction at the benzylic positions, yielding aromatic ketones265 or aromatic aldehydes.266 These oxidations normally demand quite harsh conditions with excess of PCC, long reaction times and high temperature. Therefore, they hardly compete with the oxidation of alcohols, which is normally made under quite mild conditions. 

Arene(tricarbonyl)chromium complexes undergo a number of synthetically important transformations not usually observed for uncomplexed arenes. The chromium tricarbonyl moiety facilitates nucleophilic, electrophilic, and radical reactions at the benzylic position. Upon complexation, one side of the aromatic ring and adjacent functionalities is blocked by the metal carbonyl moiety and highly stereoselective reactions are usually observed even at relatively remote positions. In addition, the protons of the complexed aromatic ring have a substantially higher acidity and are readily removed and further substituted by electrophiles. Finally, the aromatic ring is activated toward addition reactions using a variety of nucleophiles. 

Like allyl- and propargylmagnesium compounds, benzylmagnesium halides when reacted with a substrate give rise in part to products substituted at the allylic, i.e., here at the ortho position THF favors reaction at the benzylic position . 

Formation of an ether at a benzylic position rather than at an alternative site by bromide ion displacement is seen in the reaction of either cis or trans-Z-bromochroman-4-ols with 4-methylphenol in the presence of equimolar proportons of diethyl azodicarboxyiate and triphenylphosphine in benzene soiution over 8 hours at ambient temperature to result in the product iilustrated in 84% yieid (from the cis intermediate) (ref. 39). 

The structural difference imposed by the smaller metal chelate rings in the complex [Cu2(L55)] , five-membered instead of six-membered as in [Cu2(L66)], determine a completely different reactivity behavior with dihydrogen peroxide (107). The complex [Cu2(L55)] , undergoes a ligand hydroxylation reaction in the presence of H2O2, but this occurs at a benzylic position and with much slower rate (Scheme 8). The involvement of a hydroperoxo complex of [Cu2(L55)] has been suggested for this reaction, though no intermediate has been characterized yet. 

The last two examples add the same group (OPr) to the same compound (an epoxide) to give different products. We can tell that the first is SnI as PrOH adds to the more substituted (tertiary and benzylic) position. Inversion occurs because the nucleophile prefers to add to the less hindered face opposite the OH group. If you said that it is an Sn2 reaction at a benzylic centre with a loose cationic transition state, you may well be right. 

The name benzyl radical is used as a specific name for the radical produced in this reaction. The general name benzylic radical applies to all radicals that have an unpaired electron on the side-chain carbon atom that is directly attached to the benzene ring (Section 10.9). The hydrogen atoms of the carbon atom directly attached to the benzene ring are called benzylic hydrogen atoms. A group bonded at a benzylic position is called a benzylic substituent. 

The 5 -(trifluoromethyl)sulfonium salt can be applied to copper-mediated trifluoromethylation. Trifluoromethylation of heteroaryl iodides with the sulfonium salt proceeds in presence of stoichiometric copper under mild condition (eqs 17 and 18). Boronic acids also react with sulfonium salt (eqs 19 and 20), though 1 equiv of NaHCOs is needed as the base. These reactions furnish corresponding trifluoromethylated products in high yield. The copper-mediated trifluoromethylation reaction advances not only with aromatic compounds, but also at a benzylic position (eq 21). Trifluoromethylation reaction of benzyl bromides with S -(trifluoromethyl) sulfonium salt provides (trifluoroethyl)arenes in high yields. 

Side-chain bromination at the benzylic position occurs when an alkylbenzene is treated with /V-bromosuccinimide (NBS). For example, propylbenzene gives (l-bromopropyl)benzene in 97% yield on reaction tvith NBS in the presence of benzoyl peroxide, (PhC02)2f as a radical initiator. Bromination occurs exclusively in the benzylic position and does not give a mixture of products. 

Reaction selectivity of the parent ortho-QM has also been explored with a variety of amino acid and related species.30 In these examples, the rates of alkylation and adduct yields were quantified over a range of temperatures and pH values. The initial QM3 was generated by exposing a quaternary benzyl amine (QMP3) to heat or ultraviolet radiation (Scheme 9.10). Reversible generation of QM3 was implied by subsequent exchange of nucleophiles at the benzylic position under alternative photochemical or thermal activation.30 Report of this work also included the first suggestion that the reversible nature of QM alkylation could be used for controlled delivery of a potent electrophile. 

In the absence of reversible reaction, for example when water acts as the lone nucleophile, QMP11 is consumed with a half-life of approximately 0.5 h as measured by its diminished ability to cross-link DNA (Scheme 9.18).69 Elimination of acetate to form the first of two possible QM intermediates (QM12) is likely rate-determining in this process since subsequent addition by water is estimated to occur with a half-life in the millisecond range.56 The resulting hydroxy substituent at the benzylic position does not eliminate and regenerate QM12 under ambient conditions. Thus, water... 

The reaction mechanisms have been clarified in some detail7In method (a) a complex sequence starts with the acetoxy cyclopropenium ion 126 and the cyclo-propenyl acetate 127 and finally leads to adducts 128 containing two moles of arylmalononitrile, which were isolated and shown to be the preferential precursors of quinocyclopropenes. In method (b) the ambivalent arylmalononitrile anion102) is reversibly attacked at the benzylic position at low temperatures, whilst at higher temperature (after dissociation of 114) attack at the o- and p-positions of the... 

The general feature of alkylation reactions at a carbon atom is that they can be achieved under sonication using solid bases even in apolar solvents. The advantage is that side reactions are generally minimised. Deprotonation occurs readily on a benzylic position in the presence of aqueous sodium hydroxide, as shown with indene (Eq. 3.21) [117]. A quantitative yield of the alkylated product can be obtained using sonication in the presence of a PTC. It was suggested that alkylation of cyclopentadiene or indene by secondary or tertiary alkyl halides in the presence of potassium hydroxide and Ali-quat occurred via a SET process [118]. 

For a few select cases, the cyclic aUcene 62a-c with simple primary alkyls as substituents were readily hydrogenated with SimplePHOX ligand 7a and 7c. Importantly, no epimerization at the benzylic position was observed, and hydrogenation gave entirely cis product with most substrates. Aromatization of the dihydronapthe-lene substrates 63a-b was a frequent side reaction, even at high pressures. 

Two precedent examples had been reported of the enantioselective [2+2+2] cycloaddition of alkynes. In one case, an enantioposition-selective intermolecular reaction of a triyne with acetylene generated an asymmetric carbon at the benzylic position of a formed benzene ring [19]. In the other case, an intramolecular reaction of a triyne induced helical chirality [20]. Both reactions were developed by chiral Ni catalysts. 

A possible mechanism of oxidation of methylene groups to carbonyl groups involves autoxidation (oxidation by molecular oxygen) at the benzylic position. Autoxidation of arylalkanes is a facile reaction with low activation energies for example, 6.0 kcal/mole for 1,1-diphenylethane and 13.3 kcal/mole for toluene. ... 

Benzenechromium tricarbonyl 371 is deprotonated by BuLi in EtiO-THF at —40 °C in a reaction that needs carefnl control for good yields . The prodnct 372 can be sily-lated to give 373 in 60% yield (Scheme 158). Toluenechrominm tricarbonyl lithiates non-regioselectively on the ring (bnt at the benzylic position with Na or K bases). Excess base can lead to polylithiation . 

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