Allylic etherification reactions

Although palladium catalysts have played the most prominent role in this area, other metals have also been found to catalyze allylic etherification reactions, often providing complementary stereochemical outcomes. A few ruthenium catalyst systems have been used for the O-allylation of phenols,143,144 including an enantioselective version utilizing [Cp Ru(MeCN)3]PF6 that provides promising ee s, albeit with diminished control of regioselectivity (Equation (25)).145... 

Although the majority of allylic etherification reactions have primarily utilized allylic carboxylates or carbonates as electrophiles (and occasionally allylic chlorides), the use of allylic alcohols for this transformation would be more desirable from a practical standpoint. Reported strategies involving Pd catalysis include the use of P(OPh)3 as the ligand197 and Ti(OPf)4198 as an additive for the in situ activation of the hydoxyl group (Equation (49)).199... 

Transition metal-catalyzed allylic substitution with phenols and alcohols represents a fundamentally important cross-coupling reaction for the construction of allylic ethers, which are ubiquitous in a variety of biologically important molecules [44, 45]. While phenols have proven efficient nucleophiles for a variety of intermolecular allylic etherification reactions, alcohols have proven much more challenging nucleophiles, primarily due to their hard, more basic character. This is exemphfied with secondary and tertiary alcohols, and has undoubtedly limited the synthetic utihty of this transformation. 

Enantiospecijic Rhodium-QjtalYzed Allylic Alkylation 207 Tab. 10.8 The scope of the regioselective rhodium-catalyzed allylic etherification reaction. 

Rhodium catalysts have also been used with increasing frequency for the allylic etherification of aliphatic alcohols. The chiral 7r-allylrhodium complexes generated from asymmetric ring-opening (ARO) reactions have been shown to react with both aromatic and aliphatic alcohols (Equation (46)).185-188 Mechanistic studies have shown that the reaction proceeds by an oxidative addition of Rh(i) into the oxabicyclic alkene system with retention of configuration, as directed by coordination of the oxygen atom, and subsequent SN2 addition of the oxygen nucleophile. 

Another Rh-catalyzed protocol that has potentially broad utility has come from the reactions of Cu(i) alkoxides with allylic carbonates.190,191 Under the action of Wilkinson s catalyst modified by P(OMe)3, a variety of primary, secondary, and even tertiary aliphatic alcohols undergo an allylic etherification process with a high degree of retention of regio- and stereochemistry, thus providing expeditious access to a and/or ct -stereogenic ether linkages (Scheme 5).192... 

In addition to alkoxides, carbonyl oxygens have occasionally been recruited to function as nucleophiles in allylic etherification processes. The cyclization reactions of ketones containing internal allylic systems occur through O-allylation under Pd catalysis to give rise to vinyl dihydrofurans203 or vinyl dihydropyrans (Equation (51))204,205 in good yields. 

Disubstituted dihydrofurans and dihydropyrans were prepared via allylic etherification [68] in a similar manner to dihydropyrroles (cf Section 9.4.6). Thus, diaste-reoisomeric ethers were generated by the reaction of cinnamyl tert-butyl carbonate with the copper alkoxide prepared from (Rj-l-octen-3-ol, depending on which enantiomer of the phosphoramidite ligand was used (Scheme 9.39). Good yields and excellent selectivities were obtained. RCM in a standard manner gave cis- and trans-dihydrofuran derivatives in good yield, and the same method was used for the preparation of dihydropyrans. 

Tab. 10.7 summarizes the results of the application of rhodium-catalyzed allylic etherification to a series of ortho-substituted phenols. The etherification tolerates alkyls, including branched alkanes (entries 1 and 2), aryl substituents (entry 3), heteroatoms (entries 4 and 5), and halogens (entry 6). These results prompted the examination of ortho-disubstituted phenols, which were expected to be more challenging substrates for this type of reaction. Remarkably, the ortho-disubstituted phenols furnished the secondary aryl allyl ethers with similar selectivity (entries 7-12). The ability to employ halogen-bearing ortho-disubstituted phenols should facilitate substitutions that would have proven extremely challenging with conventional cross-coupling protocols. 

Rhodium-catalyzed allylic etherification could also be extended to the more challenging tertiary alcohols (Eq. 7). Although preliminary attempts revealed that the alkylation of the allylic carbonate 51 was feasible, the reaction required increased catalyst loading (20 mol%), affording the allylic ether 52 in 67% yield (2° 1°=47 1). 

A commonly used hydrophilic polymer block in amphiphilic block copolymers is poly(ethylene oxide) (PEO). An end-functionalized PEO block was prepared by an etherification reaction between an OH-terminated polyethylene oxide of a defined block length and allyl bromide under basic conditions. 

Etherification of hindered tribromophenol with allyl bromide Reaction of sodium sulfide with benzyl chloride Reaction of amino acids and methanesulfonyl chloride Dichlorovinylation of carbazole in solid-liquid system... 

Different compounds such as epoxides and allyl chloride are used in this important modification of phenolic resins. Epoxides are one key component for phenolic resin modification by an etherification reaction. Technological important reactions are the conversion of novolacs into epoxy novolacs and the ctosslinking of phenolics with epoxy resins. Recently, hydroxymethyl-group-containing phenolics have been converted into epoxides. 

As mentioned earlier, oxazolines can be hydrolyzed in the presence of strong bases to the corresponding N-(2-hydroxyethyl)amides, and also can react with weak electrophiles like benzyl bromide or allyl chloride to give poly(N-acylethyleneimines). Therefore, if the etherification reaction is... 

Etherification of Sucrose Chelates by Allyl Halides, and Sodium Bromoacetate, Allyl bromide or chloride was added to a dimethylsulphoxide (DMSO) solution of sucrose chelate in the ratios of sucrose allyl halide 1 1,1, 1 1,3, 1 2,0 and 1 2,5 and kept at 80°C for 16 to 48 h. The allyl bromide reactions were carried out in screw cap, sealed test tubes and most of the allyl chloride reactions in a sealed autoclave. Decomposition of the sucrose was prevented by keeping the ratio of sucrose to allyl halide equal or less than the ratio 1 2,5. The reaction between sucrose chelates and sodium bromoacetate was performed in the following ratios sucrose bromoacetate, 1 2,6, 1 3,8, 1 5,2 and 1 7,0, in DMSO for 72 h at 70°C. 

In order to complement earlier studies showing that IV-alkyl-substituted ben-zimidazolylidene-ruthenium complexes were efficient catalysts for the regiose-lective alkylation of cinnamyl carbonate by dimethyl malonate or 1,3-diketones, as well as etherification of allylic halides by phenols, Bruneau and co-workers prepared a wide range of imidazolinium 38, tetrahydropyrimidinium 39, and benzimidazolium salts 40 that were screened as NHC ligand precursors in various allylic substitution reactions (Equation (7.9)). Unfortunately, linear versus branched selectivities were only modest, and no characterisation of the [(NHC)Ru(Cp )] complexes assumed to take part in the reaction could be achieved, thereby preventing any further rational ligand modification that would have helped refine the catalytic system. 

Several methods and reaction pathways have been reported for the conversion of glycerol in the literature, such as etherification, esterification [1], and oxidation [2], Via ionic dehydration acetol [3] and acrolein can be produced. The radical steps result in aldehydes, allyl alcohol, etc. [4], If the dehydration is followed by a hydrogenation step, propanediols (1,2- or 1,3-) can be obtained [5-6]. 

In carbohydrate chemistry, the preparation of ethers that are stable in the presence of acids, bases, and aqueous alkali is an important analytical and synthetic tool. The methods used for the etherification of hydroxyl groups51 generally employ reactions of unprotected sugars and glycosides with methyl, allyl, benzyl, triphenylmethyl, and alkylsilyl halides in the presence of a variety of aqueous and nonaqueous bases. 

Since nucleophilic addition to a metal-coordinated alkene generates a cr-metal species bonded to an -hybridized carbon, facile 3-H elimination may then ensue. An important example of pertinence to this mechanism is the Wacker reaction, in which alkenes are converted into carbonyl compounds by the oxidative addition of water (Equation (108)), typically in the presence of a Pd(n) catalyst and a stoichiometric reoxidant.399 When an alcohol is employed as the nucleophile instead, the reaction produces a vinyl or allylic ether as the product, thus accomplishing an etherification process. 

Catalysts lacking phosphorus ligands have also been used as catalysts for allylic substitutions. [lr(COD)Cl]2 itself, which contains a 7i-accepting diolefin ligand, catalyzes the alkylation of allylic acetates, but the formation of branched products was only favored when the substitution reaction was performed with branched allylic esters. Takemoto and coworkers later reported the etherification of branched allylic acetates and carbonates with oximes catalyzed by [lr(COD)Cl]2 without added ligand [47]. Finally, as discussed in Sect. 6, Carreira reported kinetic resolutions of branched allylic carbonates from reactions of phenol catalyzed by the combination of [lr(COE)2Cl]2 and a chiral diene ligand [48]. 

Although the Ir-catalyzed aUyhc substitution was developed only recently, several applications in the areas of medicinal and natural products chemistry have aheady been reported. In many syntheses the allylic substitution has been combined with a RCM reaction [71]. Examples not directed at natural products targets have aheady been described in Sections 9.4 and 9.5. It has also been mentioned that this strategy had previously been used in conjunction with aUyhc substitutions catalyzed by other transition metals (Figure 9.5). This was pioneered by P. A. Evans and colleagues, who used Rh-catalyzed allylic amination (compound A in Figure 9.5) [72] and etherification (compound B) [73], while Trost and coworkers demonstrated the power of this concept for Pd-catalyzed aUyhc alkylations (compound C) [74] and Alexakis et al. for Cu-catalyzed (compound D) aUyhc alkylations [75]. 

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 ... 

Etherification. The reaction of alkyl halides with sugar polyols in the presence of aqueous alkaline reagents generally results in partial etherification. Thus, a tetraallyl ether is formed on reaction of D-mannitol with allyl bromide in the presence of 20% sodium hydroxide at 75°C (124). Treatment of this partial ether with metallic sodium to form an alcoholate, followed by reaction with additional allyl bromide, leads to hexaallyl D-mannitol (125). Complete methylation of D-mannitol occurs, however, by the action of dimethyl sulfate and sodium hydroxide (126). A mixture of tetra- and pentabutyloxymethyl ethers of D-mannitol results from the action of butyl chloromethyl ether (127). Completely substituted trimethylsilyl derivatives of polyols, distillable in vacuo, are prepared by interaction with trimethylchlorosilane in the presence of pyridine (128). Hexavinylmannitol is obtained from D-mannitol and acetylene at 25.31 MPa (250 atm) and 160°C (129). 

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