Benzyhc

The benzyhc position m alkylbenzenes is analogous to the allyhc position m alkenes Thus a benzyhc C—H bond like an allyhc one is weaker than a C—H bond of an alkane as the bond dissociation energies of toluene propene and 2 methylpropane attest... 

Benzene with no alkyl side chain and no benzyhc hydrogens undergoes a different reaction under these conditions Oxidation of the ring occurs to convert benzene to its epoxide... 

Primary benzyhc halides are ideal substrates for Sn2 reactions because they are very reactive toward good nucleophiles and cannot undergo competing elimination... 

Acid catalyzed dehydration of benzyhc alcohols is a useful route to alkenylben zenes as is dehydrohalogenation under E2 conditions... 

The aromaticity of the nng is retained when chlorine bonds to the benzyhc carbon aro maticity is lost when chlorine bonds to one of the ring carbons... 

The unique chemical behavior of KO2 is a result of its dual character as a radical anion and a strong oxidizing agent (68). The reactivity and solubiHty of KO2 is gready enhanced by a crown ether (69). Its usefiilness in furnishing oxygen anions is demonstrated by its appHcations in SN2-type reactions to displace methanesulfonate and bromine groups (70,71), the oxidation of benzyHc methylene compounds to ketones (72), and the syntheses of a-hydroxyketones from ketones (73). 

The benzyhc complex has been synthesized at low temperatures and may owe its stabiUty to possible multihapto coordination, Tj —Tj, of the benzyl ligand. The methyl complex is stable even up to room temperature. Six of the methyl groups are hydrogen-bonded to the Li atom to stabilize this highly charged species. This compound is very reactive with and CO. However, there is no concrete stmctural data for the final products of such reactions. 

Whereas benzyhc hydroxyl functions such as in benzyl alcohol are converted by TIS 17 into benzyl iodide 1734 [2, 7] and HMDSO 7 and I2, 1-phenylethanol 1735 [8] is reduced in high yields on longer reaction times with excess TIS 17 via the iodide 1736 to give ethylbenzene 1737 [7-11] (Scheme 12.2). Ether cleavage of 1738 with TIS 17 affords, via 1739a and 1739b, the bicyclic compound 1740 in... 

Styrene hydrozirconation led to a ratio for terminal and benzylic zirconocene products of around 85 15 [97]. Experimental evidence on alkyl-substituted styrene suggested that both electronic [98,99] and steric effects [41,86] are important for the formation of the benzyhc and terminal zirconium isomers. Migration of the metal fragment during the reaction of the zirconocene moiety might occur, perturbing the terminal/benzyl regioisomer ratio of the isolated products (Scheme 8-11) [67, 83, 98-102]. 

Compound 1 was the first cyclopentane-based NK-1 receptor antagonist development candidate at Merck. It contains five stereocenters a central core possessing three contiguous all-trans stereocenters, a pendent bis(trifluoromethyl)-benzyHc ether, and a nipecotic acid moiety (Figure 7.1). Key to the successful preparation of 1 was construction of the trans, trans-cyclopentyl core and installation of the unsymmetrical secondary-secondary (sec-sec) ether. The preparation of 1 is the focus of this chapter. 

In the case of the steroid (38), anodic substitution allowed the selective substitution of the benzyhc hydrogen atom by a methoxy group, whose elimination afforded (39) and overall led in a three... 

A heterogeneous and recyclable palladium catalyst, Pd/A10(OH), is excellent for the racemization of primary amines. We have demonstrated successful DKR of various primary amines by combining the palladium catalyst and a lipase to produce the corresponding (/ )-acetamides in high yields and in high optical purities. Tables 4.3 and 4.4 show the results of the DKR of benzyhc and aliphatic primary amines. 

The enantioselective benzylic hydroxylation of indan and tetralin can be achieved with M. isabellina, affording 78 % conversion to 1-indanol (64 % yield, 86 % (11 )- ee) in a 2-day incubation and 52 % conversion to 1-tetralol (38 % yield, 92 % (11 )- ee) in a 4-day incubation. The good yields and ee allow their use in future scahng-up processes however, to avoid the lack of efficiency, careful control of the temperature, pH and medium is necessary, since the reactions are strongly dependent on the incubation and reaction conditions. Tables 12.2 and 12.3 give details of some of the different incubation condi-tions/results and time-course analysis found in the benzyhc hydroxylation of indan and tetrahn mediated by M. isabellina CCT3498. 

In addition, Mg/Al and Co/Al LDHs containing Ru + in the layers have also been used as precursors to mixed oxides that are highly efficient catalysts for the oxidation of allylic and benzyhc alcohols [73,74]. 

Ley et al. performed oxidations of activated (benzyhc, allylic) alcohols by employing polymer-attached perruthenate catalysts and oxygen as oxidant. Triethylammo-... 

It was observed that in the case of bromo- or iodo-substituted benzyhc tellurides the lithium-Br exchange and/or the halogen displacement by the n-butylhthinm competes with the Te-Li exchange, resulting in lower yields of the desired products. This drawback is avoided by using ether as solvent. 

ALkoxyalkyl-substituted arenechromium complexes have been lithiated enantioselec-tively in the benzylic position without control over planar chirahty and the tendency for lithium amides to lithiate at a benzyhc position rather than on the ring itself poses a problem with some substrates. In the lithiation of 433, an element of planar stereochemistry is introduced during a benzyhc lithiation (Scheme 176) . Exploiting... 

While not strictly a directed metallation, an important early example of enantioselective lithiation in a benzyhc position was the lithiation of the achiral biaryl 598 using n-BuLi-(—)-sparteine. The product 599 of unknown configuration was obtained in moderate ee (Scheme 236) . ... 

Comparison of the configuration of the stannane with the prodncts of reaction reveals that primary alkyl halides that are not benzyhc or a to a carbonyl react with inversion at the lithium-bearing carbon atom. In the piperidine series, the best data are for the 3-phenylpropyl compound, which was shown to be >99 1 er. In the pyrrolidine series, the er of the analogous compound indicates 21-22% retention and 78-79% inversion of configuration. Activated alkyl halides such as benzyl bromide and teri-butyl bromoacetate afford racemic adducts. In both the pyrrolidine and piperidine series, most carbonyl electrophiles (i.e. carbon dioxide, dimethyl carbonate, methyl chloroformate, pivaloyl chloride, cyclohexanone, acetone and benzaldehyde) react with virtually complete retention of configuration at the lithium-bearing carbon atom. The only exceptions are benzophenone, which affords racemic adduct, and pivaloyl chloride, which shows some inversion. The inversion observed with pivaloyl chloride may be due to partial racemization of the ketone product during work-up. 

We believe that the selectivity of methine (CH) insertion over methylene (CH2) insertion (Tab. 16.6) is a reflection of the polarizabihty of the rhodium carbenoid. As the carbenoid approaches the target C-H, the methine C-H is more electron-rich than the methylene C-H. A more easily polarized carbenoid would respond more fully to this and give proportionally more of the methine insertion product. Our design of the a-diazo ester 32 included the p-methoxy group on the benzene ring, so that the reactivity of the methylene benzylic C-H would approach that of the methine. Statistically, due to geometric constraints, only one of the two benzyhc methylene C-H groups is available for the insertion necessary for the cyclization to 36/37. 

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