Benzylic hydrogens, deprotonation

Benzopyrylium salts with benzylic hydrogens 57 cannot be isolated, apparently because of their tendency to deprotonate leading to the unstable heterocycles with exocyclic double bonds (Equation 20) < 1999J(P 1)1155>. 

A subsequent study ° from the Arnold group showed an intriguing stereoelectronic effect in oxidative benzylic carbon-hydrogen bond cleavage reactions of substrates 8 and 9 (Scheme 3.7). In this study, electron transfer reactions were conducted in the presence of a nonnucleophilic base. Radical cation formation also weakens benzylic carbon-hydrogen bonds, thereby enhancing their acidity. Deprotonation of benzylic hydrogens yields benzylic radicals that can be reduced by the radical anion of dicyanobenzene to form benzylic anions that will be protonated by solvent. This sequence of oxidation, deprotonation, reduction, and protonation provides a sequence by which epimerization can be effected at the benzylic center. In this study, tram isomer 10 showed no propensity to isomerize to cis isomer 11 (equation 1 in Scheme 3.7), but 11 readily converted to 10 (equation 2 in Scheme 3.7). The reactions were repeated in deuterated solvents to assure that these observations resulted from kinetic rather than thermodynamic factors. Trans isomer 9 showed no incorporation of deuterium (equation 3 in Scheme 3.7) whereas cis isomer 11 showed complete deuterium incorporation. The authors attributed this difference in reactivity to... 

Benzyl ethers are quite stable under both acidic and basic conditions and toward a wide variety of oxidizing and reducing reagents. Hence, they are frequently used in organic syntheses as protecting groups. It should be noted, however, that n-BuLi may deprotonate a benzylic hydrogen, especially in the presence of TMEDA (tetra-methylethylenediamine) or HMPA (hexamethylphosphoramide). 

In a further refinement to the synthesis, Sygula and Rabideau discovered an appealing alternative method (Method C, Scheme 4) to prepare 1,2,5,6-tetrabromo-corannulene 18 from 17 by the use of sodium hydroxide to deprotonate the remaining benzylic hydrogen and initiate carbon-carbon bond formation [36-38], The desired molecule 1 was formed (90%) by treatment of 18 with zinc and potassium iodide [37, 38],... 

The corresponding Li confound deprotonates (1) (or 20-22). With the dibenzylamine reagent (35), amination of RLi is not observed because of the comparatively fast /3-elimination to give (36) due to the rather acidic benzylic hydrogen atoms (eq 5). ... 

An efficient method for the generation of useful dilithiated aryl-alkyl sulfides has been developed. The selectivity of the Br/Li exchange depends on the acidity of the hydrogen atoms in the aliphatic position. For the hydrogen atoms in the benzylic position, the acidity is strongly influenced by the substituent in the benzene ring. The non-benzylic hydrogen atoms in the a position to sulfur are rather unreactive towards deprotonation with Bu i, unless they are flanked by two sulfur atoms. 

Sucrose Ethers. Being next to the anomeric center and intramolecularly hydrogen-bonded, the 2 -OH of sucrose is the most acidic, which means it is deprotonated first under alkaline conditions, and thus preferentially yields to etherification. Benzylation with NaH/benzylbromide in DMF, for example, results in an 11 2 1 mixture of 2 -(9-benzyl-sucrose (Figure 2.8) and its 1-0- and 3 -0-isomers. Because the former is readily accessible, it proved to be a versatile intermediate for the generation of 2 -modified sucroses, for example, the 2 -keto and 2 -deoxy derivatives as well as sucrosamine (2 -amino-2 -deoxy-sucrose), whose application profiles remain to be investigated. 

Recent studies conducted by the same group revealed that the radical cation of toluene generated by photoinduced electron transfer can be deprotonated in a protic cosolvent and thus efficient trapping by electrophilic alkenes is feasible, yielding benzylation products. Secondary hydrogen abstraction by the benzyl radical from methanol generates hydroxymethyl radicals, which can also be used for preparative hydroxymethylation of alkenes (Scheme 18) [24],... 

The indirect anodic cleavage of carbon-hydrogen bonds in the benzyl position using triarylamine mediators was also used for mild and selective deblocking of hydroxy, carboxyl, and amino groups. The primarily formed cation radical of the protective group is readily deprotonated in the benzyl position by an added base (Eq. (107)). This benzylic radical is easily further oxidized to the benzyl cation which subsequently is cleaved by attack of a nucleophile, such as water (Eq. (108)). 

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. 

Even Ar-hydrogen-4,5-dihydroimidazolcs can be side-chain deprotonated when the side-chain carbon is also benzylic thus, the N,C-dianion formed from 497 can be N,C-dialkylated producing 498, for example, <1998JOC8107>. 

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