Methyl deprotonation

For methyl ketimines good regiochemical control in favor of methyl deprotonation, regardless of imine stereochemistry, is observed using LDA at -78° C. With larger A-substituents, deprotonation at 25° C occurs anti to the nitrogen substituent.115... 

These studies indicate that the selectivity of a-aminoalkyl radical formation is Me > Et /-Pr, which is the opposite of that expected on the basis of radical stability. For example, in diisopropylmethylamine, methyl adducts are formed exclusively. Similar selectivity has been observed for oxidation of unsymmetrical amines by ferricyanide [43, 123] and in anodic processes [124]. This selectivity has been attributed to requirement of overlap between the half-vacant nitrogen p orbital and the a-CH orbital of the a-carbon. From the Newman projections below it can be seen that the conformation necessary for methyl deprotonation (a) is lower in energy than that for the isopropyl deprotonation (b) [5, 122]. 

Quantitative measures for some methyl deprotonations are 2-methylpyridine (pK 34), 3-methylpyridine (pK 37.7), 4-methylpyridine (pK 32.2), 4-methylquinoline (pK 27.5). ° These values can be usefully compared with those typical for ketone a-deprotonation (19-20) and toluene side-chain deprotonation (-41). Thus, strong bases can be used to convert methyl-pyridines quantitatively into side-chain anions, however the enolate-like stabilisation of the anion is sufficient that reactions can often be carried out using weaker bases under equilibrating conditions, i.e. under conditions where there is only a small percentage of anion present at any one time. It may be that under such conditions, side-chain deprotonation involves iV-hydrogen-bonded or iV-coordinated pyridines. 

In the case where a nonsymmetrical sulfide such as 19 is used, deuterium labeling studies using 2-deuteroisobomeol 25 indicate that it s the 5-methyl group rather than the 5-methylene that is deprotonated (second to last step of mechanism) and the fact that the deuterium label from the alcohol is transferred to this position supports the last step in the hypothesized sequence of events that is proposed. Spectral analyses confirm that the selectivity for 5-methyl deprotonation is in fact 95 5.4... 

The condensation between 2,4,6-trimethylpyrylium and 2,6-dimethyl-4-pyrone is particularly instructive the latter is converted into a 4-acetoxypyrylium (see also section 8.1.3) and the former, by 4-methyl deprotonation, into a nucleophilic dienol ether. ... 

The polymerization is in fact a chain-growth reaction and allows access to high molecular weight polyphosphazenes such as poly(dimethylphosphazene) and poly(methylphenylphosphazene) (2). Methyl deprotonation/substitution of these polymers as well as electrophilic aromatic substitution of the phenyl substituents in poly(methylphenylphosphazene) have been developed as versatile strategies for the derivatization of both of these polymers (eq. 3) (3). 

What of the feasibility of developing sequential DreM biaryl amide and O-carbamate reactions One attractive possibility (Scheme 25) involves remote anionic Fries rearrangement, 102 103 followed by remote methyl deprotonation and... 

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