Silylation reactivity-controlled

Figure 4. Silylation of porous silica beads. The fractional extent of completion of the reaction at the external surface and on the internal surface is shown on the ordinate and abscissa, respectively. The straight diagonal line shows expectation for reactivity control. The TFSA data show a high degree of pore diffusion control. (From [33], with permission from Gordon and Breach, Science Publishers S.A.)...

Silyl ethers are among the most frequently used protective groups for the alcohol function. This stems largely from the fact that their reactivity (both formation and cleavage) can be modulated by a suitable choice of substituents on the silicon atom. Both steric and electronic effects are the basic controlling elements that regulate the ease of cleavage in multiply functionalized substrates. In plan-... 

There are, however, serious problems that must be overcome in the application of this reaction to synthesis. The product is a new carbocation that can react further. Repetitive addition to alkene molecules leads to polymerization. Indeed, this is the mechanism of acid-catalyzed polymerization of alkenes. There is also the possibility of rearrangement. A key requirement for adapting the reaction of carbocations with alkenes to the synthesis of small molecules is control of the reactivity of the newly formed carbocation intermediate. Synthetically useful carbocation-alkene reactions require a suitable termination step. We have already encountered one successful strategy in the reaction of alkenyl and allylic silanes and stannanes with electrophilic carbon (see Chapter 9). In those reactions, the silyl or stannyl substituent is eliminated and a stable alkene is formed. The increased reactivity of the silyl- and stannyl-substituted alkenes is also favorable to the synthetic utility of carbocation-alkene reactions because the reactants are more nucleophilic than the product alkenes. 

The wide diversity of the foregoing reactions with electron-poor acceptors (which include cationic and neutral electrophiles as well as strong and weak one-electron oxidants) points to enol silyl ethers as electron donors in general. Indeed, we will show how the electron-transfer paradigm can be applied to the various reactions of enol silyl ethers listed above in which the donor/acceptor pair leads to a variety of reactive intermediates including cation radicals, anion radicals, radicals, etc. that govern the product distribution. Moreover, the modulation of ion-pair (cation radical and anion radical) dynamics by solvent and added salt allows control of the competing pathways to achieve the desired selectivity (see below). 

The oxidation of an amine can benefit from the use of an electroauxiliary [19-28]. Electroauxiliaries are substituents that both lower the initial oxidation potential of the substrate and control the formation of the subsequent reactive intermediates. To this end, the anodic oxidation of the 6-membered ring a-silylamines in the presence of cyanide was shown to afford a net displacement of the silyl... 

Mattay et al. examined the regioselective and stereoselective cyclization of unsaturated silyl enol ethers by photoinduced electron transfer using DCA and DCN as sensitizers. Thereby the regiochemistry (6-endo versus 5-exo) of the cyclization could be controlled because in the absence of a nucleophile, like an alcohol, the cyclization of the siloxy radical cation is dominant, whereas the presence of a nucleophile favors the reaction pathway via the corresponding a-keto radical. The resulting stereoselective cis ring juncture is due to a favored reactive chair like conformer with the substituents pseudoaxial arranged (Scheme 27) [36,37]. 

As the polymerization occurs, the reactive ketene silyl acetal group is transferred to the head of each new monomer as it is added to the growing chain (Equation 5.44). Similar to anionic polymerization, the molecular weight is controlled by the ratio of the concentration of... 

Lithium Enolates. The control of mixed aldol additions between aldehydes and ketones that present several possible sites for enolization is a challenging problem. Such reactions are normally carried out by complete conversion of the carbonyl compound that is to serve as the nucleophile to an enolate, silyl enol ether, or imine anion. The reactive nucleophile is then allowed to react with the second reaction component. As long as the addition step is faster than proton transfer, or other mechanisms of interconversion of the nucleophilic and electrophilic components, the adduct will have the desired... 

Control of the side reactions is achieved through two factors (1) reversible complexation of the anionic propagating species XXVII by the silyl ketene acetal polymer chain ends XXVI maintains the concentration of the anionic propagating species at a low concentration and (2) the bulky counterion W+ (e.g., tetra-ra-huty I ammonium, tris(dimethylamino)sulfonium) decreases the reactivity of the anionic propagating centers toward the terminating side reactions. 

Tetrahydropyranyl (THP) ethers, another species known to be unstable to acid, have similarly been reported to be cleaved by solutions of iodine in methanol.209 At room temperature, cleavage of the THP ethers was complete in 1.5 to 8 h. As with the previous example using iodine in methanol at lower than reflux temperature, TBDMS ethers were stable to these conditions. The ability to tune the reactivity of the iodine in methanol system by simply controlling the temperature is of value in selective deprotection. This is even more useful when fluorine, known to remove only silyl ethers,105 is exploited. Given that methoxymethyl ethers, essentially acetals, are known to be cleaved under acidic conditions, it seems likely they too should be subject to removal by solutions of iodine in methanol. Sundry examples of deprotections using iodine in methanol are presented in Table IV. 

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