Phenols, silyl-substituted acidity

All these steps proceed to afford free or N -substituted crystalline cytidines 6 in high yields [11] (cf. the preparation of N (tetramethylene)cytidine 6b in 95.4% yield in Section 1.1.). This simple one-pot reaction is also very easy to perform on a technical scale, as are the subsequently discussed analogous silylation-aminations of purine nucleosides and other hydroxy-N-heterocycles (cf. Sections 4.2.4 and 4.2.5). The concept of silylation-activation while simultaneously protecting hydroxyl groups in alcohols, phenols, or phosphoric acids by silylation was subsequently rediscovered and appropriately termed transient protection [16-18]. 

The linker was prepared starting from serine benzyl ester 68 according to Scheme 30. First, the hydroxyl function was protected as a silyl ether. The amino group was then reacted with phosgene to allow for further reaction with a substituted phenol (the educt). Finally, the benzyl ester was subjected to hydrogenolysis yielding unit 69, with the latter bearing a carboxylic acid function for attachment to the solid support to yield 66 ready for use in combinatorial synthesis. 

ZSM5 type zeolites were used as catalysts for the one-step synthesis of phenol hy benzene partial oxidation with nitrous oxide. Isomorphous substitution of Al ions by other trivalent metal ions revealed a high catalytic performance of the H-Ga-ZSM5 in a wide temperature range. Systematic variation of the partial pressures of the reactants led to satisfactory preliminary kinetic models. Deactivation could be reduced by postsynthetic catalyst silylation which is believed to block the strongest acid sites responsible for coke formation. 

Electron rich olefins such as (70) readily react with phenols to give the para-substituted aminals (71) which can be hydrolysed to the corresponding aldehydes. When the pura-position is blocked reasonable yields of salicylaldehydes are obtained. Further cycloadditions of tetra-alkoxyethenes with aj8-unsaturated carbonyl compounds and 1-cyanobutadienes have been studied. T6s The latter product gives a [2 4- 2] and not a [4 + 2] adduct. Addition of silyl enol ethers to nitroalkenes leads to intermediate nitronic acids (72) which on hydrolysis give 1,4-diketones. In the presence of a Lewis acid the intermediates are not isolated and good yields of the synthetically useful ketones are obtained (Scheme 46). This procedure would seem to compare favourably with alternative syntheses of these intermediates. ... 

Like silylation, acetylation is effective as a means to substitute exchangeable hydrogens in alcohols, phenols, and primary and secondary amines. The reagents used for acetylation are acid anhydrides such as acetic anhydride, propionic anhydride, or trifluoroacetic anhydride. The reaction temperatures vary between 50 and 150°C and the reaction time from 15 minutes to 2 hours. As for silylation, all traces of water must be avoided. As an example, dopamine acetylation by trifluoroacetic anhydride is presented in Figure 1.5. °... 

Shibasaki has described the use of bifunctional catalysis in asymmetric Strecker reactions, using BlNOL-derived Lewis acid-Lewis base catalyst 160 (Equation 24) [114]. The aluminum complex had previously been shown to catalyze enantioselective cyanohydrin formation (Chapter 2, Section 2.9) [115]. In the proposed catalytic cycle, the imine is activated by the Lewis acidic aluminum while TMSCN undergoes activation by association of the silyl group with the Lewis basic phosphine oxide. Interestingly, the addition of phenol as a putative proton source was beneficial in facilitating catalyst turnover. The nature of the amine employed for the formation of the N-substituted aldimine proved to be vital for enantioselectivity, with optimal results obtained for N-fluorenyl imines such as 159, derived from aliphatic, unsaturated, and aromatic aldehydes (70-96% ee) [114],... 

---