Etherification effect

An unusual sensitivity of this reaction to structure was reported by Ram and Neumeyer (51). When R = H (1), hydrogenolysis could not be effected either directly or by catalytic hydrogen transfer (13), but etherification to give 2 (R = CH3) permitted slow formation of 3, The mild conditions of hydrogenation were required to avoid racemization at the 6a-position. Hydrogenolysis is usually much more facile than is indicated by this example. 

Recently, use of LiCl/DMAc and LiCl/l,3-dimethyl-2-imidazolidinone as solvent systems for acetylation of cellulose by acetic anhydride/pyridine has been compared. A DS of 1.4 was obtained the substituent distribution in the products synthesized in both solvents was found to be the same, with reactivity order Ce > C2 > C3. Therefore, the latter solvent system does not appear to be better than the much less expensive LiCl/DMAc, at least for this reaction. It appears, however, to be especially efficient for etherification reactions [178]. It is possible, however, that the effect of cellulose aggregation is more important for its reaction with the (less reactive) halides than with acid anhydrides this being the reason for the better performance of the latter solvent system in ether formation, since it is more efficient in cellulose dissolution. 

A two-component bimetallic catalytic system has been developed for the allylic etherification of aliphatic alcohols, where an Ir(i) catalyst acts on allylic carbonates to generate electrophiles, while the aliphatic alcohols are independently activated by Zn(n) coordination to function as nucleophiles (Equation (48)).194 A cationic iridium complex, [Ir(COD)2]BF4,195 and an Ru(n)-bipyridine complex196 have also been reported to effectively catalyze the O-allylation of aliphatic alcohols, although allyl acetate and MeOH, respectively, are employed in excess in these examples. 

A heterobimetallic BINOL-Ga/Li complex 53 has been developed for the enantioselective ARO of meso-cpoxides (BINOL = l,T-bi(2-naphthol)).278 Using />-methoxyphenol as the nucleophile, this etherification reaction was observed to take place with a high level of asymmetric induction. An improved catalyst 54 has also been reported that exhibits greater stability under the reaction conditions and delivers higher yields and ee s (Equation (78)).279 A simple catalyst derived from Sc(OTf)3 and the chiral bipyridine ligand 52 has been shown to be effective for the ARO of aryl-substituted /// -epoxides with aliphatic alcohols to give high ee s (Equation (79)).280... 

A survey of Wacker-type etherification reactions reveals many reports on the formation of five- and six-membered oxacycles using various internal oxygen nucleophiles. For example, phenols401,402 and aliphatic alcohols401,403-406 have been shown to be competent nucleophiles in Pd-catalyzed 6- TZ /fl-cyclization reactions that afford chromenes (Equation (109)) and dihydropyranones (Equation (110)). Also effective is the carbonyl oxygen or enol of a 1,3-diketone (Equation (111)).407 In this case, the initially formed exo-alkene is isomerized to a furan product. A similar 5-m -cyclization has been reported using an Ru(n) catalyst derived in situ from the oxidative addition of Ru3(CO)i2... 

Blocking the C-l OH of D-fructose and L-sorbose (Scheme 25) was effected in excellent yields through regioselective isopropylidene acetalation of the free ketoses, followed by etherification (benzylation or allylation) of the remaining primary alcohol. Acid-catalyzed hydrolysis of the isopropylidene groups and condensation with HSCN efficiently produced a sole fused bicyclic OZT. 

In the dimerization of isobutene, tertiary-butyl alcohol (TBA, 2-methyl-2-propanol) has a strong role in modifying the selectivity of the reaction to Cg hydrocarbons and limits further oligomerization to C12 and Ci6 hydrocarbons [34]. Also, in the etherification of glycerol with isobutene the addition of TBA has a clear effect on the selectivity and on hydrocarbon distribution. The selectivity to ethers increased and the fraction of the Cu and Ci6 hydrocarbons decreased while the concentration of TBA was increased from 0 to 2.6 mol.%. As a conclusion, the formation of C12 and C16 hydrocarbons can be prevented in two ways either TBA should be added to the reaction mixture or the reaction should be carried out at high temperatures [8]. 

Thiolate is another class of effective nucleophile Nakamura et al. (12j have proved that thiols reacted with PVC efficiently in the presence of ethylene-diamine to give the thio-etherificated PVC and PECH. 

Examination of the stereospecificity of the etherification indicated that the reaction was subject to a dramatic halide effect (Tab. 10.9). Treatment of enantiomerically enriched allylic carbonate (R)-53 (94% ee) under optimized conditions furnished the allyl ether (R)-54 in 84% yield (2° 1° >99 1), although with poor enantiospecificity (41% cee ... 

The etherified hardwood lignin model II reacted at a similar rate as the phenolic model indicating the etherification of the phenolic group has a small effect on the reaction rate. When this reaction was repeated at 55°C with an excess formaldehyde, some mefa-hydroxymethylated products were obtained (Fig. 4B). 

Only a few examples have been reported of the etherification of alcohols with resin-bound diarylmethyl alcohols (Entry 5, Table 3.30 Entry 5, Table 3.31 [564]). Diarylmethyl ethers do not seem to offer advantages over the more readily accessible trityl ethers, which are widely used as linkers for both phenols and aliphatic alcohols. Attachment of alcohols to trityl linkers is usually effected by treating trityl chloride resin or 2-chlorotrityl chloride resin with the alcohol in the presence of a base (phenols pyridine/THF, 50 °C [565] or DIPEA/DCM [566] aliphatic alcohols pyridine, 20-70 °C, 3 h-5 d [567-572] or collidine, Bu4NI, DCM, 20 °C, 65 h [81]). Aliphatic or aromatic alcohols can be attached as ethers to the same type of light-sensitive linker as used for carboxylic acids (Section 3.1.3). 

A Dieckmann reaction of 7 and enol etherification provided trans-octalone 6 in 90% yield. An additional 10% of the transposed /3-ethoxy -enone 24 was also isolated. Compound 24 could easily be removed chromatographically (the first chromatography of the synthesis) and could be isomerized back to the 9 1 mixture in favor of 6 by resubjection to the etherification conditions. Compound 7 had three different CC Et groups, yet only the one adjacent to the CN group was attacked by the nascent ketone enolate. This selectivity, attributed to the effect of the powerfully electron-withdrawing CN group, was expected, as it was observed previously in the preparation of 3c.3 The selectivity of the enol ether formation was also expected from previous work. 

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