Ethers activation

C-Glucosidation. Reaction of the protected a-D-glucopyranosyl chloride 1 with silyl enol ethers activated with AgOTf results in a-C-glucosyl esters or ketones. 

Colombo and co-workers also developed an oxazoline glycosylation method wherein an acetate is replaced by a vinyl ether. Activation of 55 with iodine in the presence of DBU gave the oxazoline 56. Glycosylation of 56 with a second sugar moiety using TMSOTf afforded the disaccharide 56a in 79% yield (Scheme 8.21). 

The reduction of benzyl aryl ethers has been thoroughly investigated by voltammetric reduction, homogeneous redox catalysis,and currently, by convolution analysis. A family of ethers activated by proper substitution on the phenoxy side were chosen to provide a wide variation in the ET and bond cleavage properties of the molecule. ... 

Entry 9 in Table 3.13 is an example of a safety-catch linker, which requires activation by TFA-mediated cleavage of a tert-butyl ether. The unactivated 2-(tm-butoxyj-phenyl esters are cleaved by amines 700 times more slowly than the corresponding 2-hydroxyphenyl esters [289]. A similar linker has been described [290], in which a benzyl ether is used instead of a ferf-butyl ether. Activation of this linker by debenzy-lation was achieved by treatment with HF or HBr/TFA [290]. 

While polar protic solvents, such as MeOH, strongly retard reaction,33 phase transfer catalysis using benzene34 or addition of crown ethers to potassium alkoxides in benzene33 allows reaction at 25 C. Even with strong electron donors, such as alkyl, methoxy or dialkylamino in the ortho, meta or para positions, substitution for chloride by potassium methoxide proceeds smoothly using the crown ether activation in benzene (equation 8).33... 

The addition of small amounts of a polar solvent can markedly alter the copolymerization behavior of, for example, the diene-styrene pair. The solvation of the active centers manifests itself in two ways the incorporation of styrene is enhanced and the modes of diene addition other than 1,4 are increased 264,273). Even a relatively weak Lewis base such as diphenyl ether will bring about these dual changes in anionic copolymerizations, as the work of Aggarwal and co-workers has shown 260>. Alterations in polyisoprene microstructure and the extent of styrene incorporation were found for ether concentrations as low as 6 vol. % (diphenyl ether has been shown52) to cause partial dissociation of the poly(styryl)lithium dimers. The findings of Aggarwal and co-workers 260) are a clear demonstration that even at relatively low concentrations diphenyl ether does interact with these anionic centers and further serve to invalidate the repetitive claim 78,158-i60,i6i) tjjat diphenyl ether — at an ether/active center ratio of 150 — does not interact with carbon-lithium active centers. 

D. J. van Unen, J. F. Engbersen, and D. N. Reinhoudt, 2002, Why do crown ethers activate enzymes in organic solvents Biotechnol. Bioeng. 77, 248-255. 

Oftentimes, even weak Lewis acids can accomplish the deprotection of methyl ethers activated by proximate carbonyl groups. For example, the last step in a synthesis of the protein kinase C inhibitor Calphostin A [Scheme 4,104]177 178 entailed regioselective cleavage of two phenolic methyl ethers using magnesium iodide in THF.179 The method is compatible with benzyl esters, N-Boc groups and N. 0-acetals,180... 

CV0.3 kPa) in refluxing toluene with azeotropic removal of water. A significant impediment to the use of both the stannylene and tributylstannyl ether activation procedures is the generation of large amounts of non-polar tin byproducts that require chromatographic separation. 

Ethers Activated carbonyl compounds undergo reductive coupling on treatment with EtjSiH in the presence of BiBrj. With silyl ethers heterocoupling of carbonyl compounds occurs. 

C-O bonds of the alkoxides Cp 2LnOEt were cleaved also by [Cp 2Ln(/r-H)]2 to give bimetallic complexes [Cp 2Ln]2(/r-0). The structure of the THF adduct [Cp 2Ce(THF)]2(/r-0) was determined by X-ray diffraction. The complex consists of two Cp 2Ce fragments linked by a nearly linear oxygen bridge. In contrast to ethers, activation of organic sulfides by [Cp 2Y(/t-H)]2 led to the corresponding metallation products (Scheme 143). 

Thomas has reported elegant studies of transmetalations in the course of allylation reactions with aldehydes. As illustrated in Scheme 5.2.47, chiral, non-racemic 207 undergoes transmetalation with SnCU to provide stabilization of the trichlorostannyl species 208 by vicinal coordination with the benzyl ether. Activation of aldehyde and addition proceeds via the closed, chair-like transition state 209. The features of the four-membered metallocycle 209 account for the exclusive formation of the Z-homoallylic alcohol and the observed 1,5-xyn-diastereoselection in 210. Similar results are obtained with ethers that have coordinating capabilities (PMB and MOM). 

The pH dependence of the hydrolysis of all compounds studied is, in principle, consistent with the mechanism of Scheme 6 that applies to the alkoxyphenylcarbene complexes, and so are the products of the reactions of 68, 66 and 8. However, the products obtained in the hydrolysis of 144 and the fact that in basic solution the hydrolysis of all the compounds is subject to a substantial kinetic solvent isotope effect are inconsistent with Scheme 6, at least at pH >8.5. The mechanism that accounts best for all experimental observations at pH >8.5, including the isotope effect, is shown in Scheme 17 for the example of 68. It involves rapid deprotonation of 68 followed either by slow protonation of 135 with water ( 2 )) or a buffer acid (fe [BH]) and subsequent rapid conversion of 161 to 162, or slow concerted water (fe2c) or buffer acid catalyzed (fe [BH]) conversion of 135 to 162 (more on these two alternatives below). Complexation between (CO)sCr and the enol ether activates the latter toward basic hydrolysis which rapidly leads to the vinyl alcohol and tautomerization to the aldehyde. Control experiments demonstrated that the kind of complexation indicated by 162 indeed promotes rapid hydrolysis of the enol ether. ° In the reactions of 144 complexation of the enol ether ()8-methoxystyrene) appears to be weak, presumably because of steric crowding, and hence the reaction... 

Crystals, mp 207 (dec), uv max (water) 217 290 nm (E]ljf 476, 190). Sol in waler, alcohols, acetone, butyl acetate, chloroform, benzol practically insol in petr ether. Activity is influenced by the change of pH being most stable at pH 7.0, relatively stable at pH 8-9 and pH 6 loses biological activity quickly when pH is reduced to < 5.0, Activity also influenced by temp change heating in boiling water for 15 min at pH 7.0 causes activity to drop. 

Alkyl silyl ethers. Activated commercial LiH promotes reductive silylation of carbonyl compounds in very high yields in the presence of McsSiCl and Zn(OTf)2. 

Side chain benzoyloxylation of aryl methyl ethers. Activation of the C-H bond is achieved in the presence of oxygen and BZ2O, giving excellent yields of the benzoates. 

The opinion has also been expressed that the viscometric technique will overestimate the degree of dissociation in systems where the dissociation constants involving the influence of ethers are studied. This claim can be examined by considering a simple example. Bywater and Worsfold and Meier studied the influence of tetrahydrofuran on the propagation rate of styrene in benzene. Their kinetic results can be interpreted as showing that at an ether/active center ratio of about 10, the poly(styryl)li ium dimers were largely disrupted by solvation with the ether for the process shown in Eq. (11). This joint conclusionis identical to that reached by Morton via the viscometric technique. Thus, at least for the case of poly(styryl)lithium, the viscometric procedure does not appear to overestimate the extent of dimer dissociation. 

---