Metalation benzylic positions

Although deprotonation at the benzylic position of arenes coordinated to ruthenium and chromium was reported,27 in the case of the coordinated oxo-ri5-dienyl unit, nucleophilic attack at one terminus of the complexed r 5-dienyl ligand, rather than deprotonation, was expected.28 The reason for the successful deprotonation (even at relatively hindered isopropyl sites) is, according to the authors, the cationic nature of the Cp M fragment. In addition, the transition state for the deprotonation might involve stabilization by the metal (Scheme 3.15). 

Tertiary butylhydroperoxide (TBHP) is a popular oxidizing agent used with certain catalysts. Because of its size, TBHP is most effective with catalysts containing large pores however, it can also be used with small-pore catalysts. Using first-row transition metals, Cr and V, impregnated into pillared clays, TBHP converts alcohols to ketones, epoxidizes alkenes, and oxidizes allylic and benzylic positions to ketones.83-87... 

An appropriately functionalized isoquinoline (38) bearing a benzyl group is prepared from an aromatic aldehyde (37). The benzyl position is metalated with LDA and the resulting carbanion is reacted with a highly substituted methyl benzoate to produce a ketone (39). The isoquinoline nitrogen is alkylated with ethyl a-bromoacetate and the resulting quaternary salt is cyclized... 

Acyloxylation has also been achieved with metallic acetates such as lead tetraacetate,237 mercuric acetate,238 and palladium(II) acetate.239 In the case of the lead and mercuric acetates, not only does the reaction take place at allylic and benzylic positions and at those a to an OR or SR group but also at positions a to the carbonyl groups of aldehydes, ketones, or esters and at those a to two carbonyl groups (ZCH2Z ). It is likely that in the latter cases... 

As shown by the last reaction in Scheme 5.23, the metalation of benzamides is complicated by several potential side reactions (Scheme 5.24). Thus, benzamides can also undergo ortho-metalation [181, 217-222] or metalation at benzylic positions [223-225], Ortho-metalation seems to be promoted by additives such as TMEDA, and benzylic metalation can be performed selectively with lithium amide bases [217,224], which are often not sufficiently basic to mediate ortho- or a-amino metalation. If deprotonation of the CH-N group succeeds, the resulting product might also undergo cydization by intramolecular attack at the arene [214, 216] (see also Ref. [226] and Scheme 5.27) instead of reacting intermolecularly with an electrophile. That this cydization occurs, despite the loss of aromatidty, shows how reactive these intermediates are. 

Similarly, benzyl ethers can be metalated either at the benzylic position or at the arene (Scheme 5.49). As with benzylic amines it seems that benzylic deprotonation is kinetically favored, whereas the metalated arene is the thermodynamically more stable product. The metalation of benzyl alcohols is discussed in Section 5.3.7.2. 

Efficient methods for optional metalation of l-(mefhylphenyl)pyrroles in a of benzylic positions./. Chem. Res. (S) 2003,132—133. 

Direct borylation of hydrocarbons catalyzed by a transition metal complex has been extensively studied by several groups and has become an economical, efficient, elegant, and environmentally benign protocol for the synthesis of a variety of organoboron compounds. The Rh-, Ir-, Re-, and Pd-catalyzed C-/H borylation of alkanes, arenes, and benzylic positions... 

Metalation of the phenyl-substituted cis-aziridine 25 followed by methyl iodide quench afforded the tricyclic isothiazole 1,1-dioxide 26 as a single diastereoisomer in 75% yield. The reaction was proposed to proceed via metalation of the benzylic position of the aziridine, rather than the position a to the silicon. Subsequent intramolecular attack of the benzylic anion 27 at the tosyl group ortho to the sulfonyl group gave 28 which was trapped with Mel to give the single diastereoisomer 26, whose structure was confirmed by X-ray analysis <02JOC2335>. 

Results of molecular modeling show that the proposed geometry of the H-bonded COOH HOOC-complex with (R,S)-2-(4-isobutyl-phe-nyl)-propanoic acid (known as ibuprofen) positions the remote CH2 group close to the active metal site, and consequently, this position should be preferentially oxidized. When racemic 2-(4-isobutyl-phenyl)-propanoic acid is brought in contact with the catalyst, the selectivity for oxidation at the remote benzylic position is greater than 98%. 

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. 

Transmetabttwn activator (2, 403). Mctalations of certain secondary benzyl-amines occur more efliciently using TMEDA-activated n-butyllithium than in mctalations with n-hutyllithium alone. Thus N-methylbenzylamine undergoes dimetalation with n-butyllithium-TMEDA predominantly at the nitrogen and o-benzyl positions. Metalation of olefins. Metalation of 1,1-dime hyl-2,2-diphenylethylene (1) with n-BuI.i-TMEDA complex gives the anion (2) in good yield as shown by the reaction... 

As a general rule, oxygen substituents are lost from benzylic positions during metal-ammonia reductions. An important set of exceptions are those compounds which possess a methoxy group in a para relationship to the benzylic substituent. Thus, 4-methoxybenzyl alcohol (208) may be reduced in high yield... 

The relative product ratios of the regioisomers 6 and rac-5 varied according to the reaction conditions. The highest (relative) amount of compound 6(11 1 product ratio) was found using the polar solvent THF, and the product ratio most in favor of rac-5 (2.4 1) was found in the non-polar solvent n-pentane. We made a similar observation during the lithiation of benzyldimethyl-(piperidinomethyl)silane [Ig]. When benzyldimethyl(piperidinomethyl)silane was treated with 1 equiv of fert-butyllithium in n-pentane or toluene at -90 °C, one of the methyl groups was lithiated selectively. Selective metalation of the benzyl position under formation of 1 occurs only when the same reaction is carried out in a polar donor solvent, such as THF. 

Methylnaphthalenes are metallated at the benzylic position with a 2-Me more reactive than a 1-Me, e.g., as found in l,2,3,4-tetramethylnaphthalene . 1,8-Dimethyl-naphthalene is only monometallated by xs n-BuLi at a methyl group, although the related compound, acenaphthyrene, is dimetallated ... 

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