Ether Formation using Epoxides

Epoxide is a common crosslinker to prepare HA hydrogels. Malson and Lindqvist patented the crosslinking of HA using butanediol diglycidyl ether (BDDE) in a 0.25 M sodium hydroxide (NaOH) solution [38]. BDDE is used for most crosslinked HA hydrogels 

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Numerous studies have been directed toward expanding the chemistry of the donor/ac-ceptor-substituted carbenoids to reactions that form new carbon-heteroatom bonds. It is well established that traditional carbenoids will react with heteroatoms to form ylide intermediates [5]. Similar reactions are possible in the rhodium-catalyzed reactions of methyl phenyldiazoacetate (Scheme 14.20). Several examples of O-H insertions to form ethers 158 [109, 110] and S-H insertions to form thioethers 159 [111] have been reported, while reactions with aldehydes and imines lead to the stereoselective formation of epoxides 160 [112, 113] and aziridines 161 [113]. The use of chiral catalysts and pantolactone as a chiral auxiliary has been explored in many of these reactions but overall the results have been rather moderate. Presumably after ylide formation, the rhodium complex disengages before product formation, causing degradation of any initial asymmetric induction. 

The formation of epoxides, the intramolecular ether, is useful in synthesis where it is desired to activate a molecule for further reactions. For example, the double bonds of an olefin are an excellent site for the introduction of an epoxide group. The energy stored in the three-member ring of an epoxide leads to higher reactivity than would be observed with an olefin. This technique is used to advantage with oleochemical substrates. 

Homologation of ketones (1, 369-370 6, 252-253 8, 222). Ethyl diazoacetate is recommended as the most useful diazoalkane for monohomologation of cyclic and acyclic ketones without formation of epoxides as by-products. One advantage is that the usually slow reaction can be catalyzed by BF3 etherate (or triethyloxonium tetrafluoro-borate). 

The authors used (5)-carvotanacetone (dihydrocarvone) as starting material (Scheme 34). To prepare the linearly conjugated sUylenol ether, they used the Kharash protocol and attained y-alkylation by Mukaiyama aldol reaction with trimethylorthoformate (195). The ketoacetal 295 was a-hydroxylated according to Rubottom by silylenol ether formation followed by epoxidation and silyl migration. Acid treatment transformed 296 to the epimeric cyclic acetals 297 and 298. endo-Aceta 297 was equilibrated thereby increasing the amount of exo-acetal 298. The necessary unsaturated side chain for the prospected radical cyclization was introduced by 1,4-addition of a (trimethylsilyl)butynylcopper compound. 

Different competitive processes are dependent on the diazo compound, on the unsaturated system, and on the solvent. With 1,1,1-trifluorobutan-2-one and diazomethane, the corresponding oxirane is formed almost exclusively. While methyl trifluoropyruvatc reacts with diazomethane to provide a mixture of the oxiranes, reaction of the pyruvate with ethyl diazoacetate provides a stable [3-1-2] cycloadduct.Chiral fluoroalkyl-substituted /i-oxo sulfoxide (e.g., 1) readily react with diazomethane to provide the corresponding chiral epoxides. Use of methanol as solvent favors oxirane formation over the competitive enol ether formation. 

The generation of 3-hydroxypropionitrile from ethylene oxide and HCN in a closed vessel was described in 1878. As the reactivity of epoxides exceeds that of acyclic ethers considerably, oxiranes do represent useful starting materials for hydroxynitriles and their derivatives. For laboratory preparations, the use of alkali metal cyanides (Scheme 13) - instead of HCN will be more convenient. The syntheses of (14) and (15) (Scheme 13) were accomplished in a buffered (MgS04) aqueous solution at about pH 9.5. The intermediate formation of epoxides on treatment of 2-halo alcohols with CN ions has already been mentioned in Section 1.8.1.2.1.ii. 

This approach can use the inherent regioselectivity of silyl enol ether formation (chapter 3) using kinetic or thermodynamic enolisation. Hence kinetic enolisation of enones (chapter 11) occurs on the a side leading to 2-Me3SiO-butadienes such as 222. Epoxidation of this silyl enol ether gives the unstable silyloxy ketone 223 which can be desilylated by fluoride ion and hence transformed into the hydroxyketone 225 or acetoxy ketone 224. These transformations are useful because the hydroxy ketones can be unstable34 (see below). 

This reagent is very useful for the dehydration of alcohols and the formation of olefins and cyclic ethers (e.g., epoxides, oxetanes, and THE). 

Boron trifluoride is a highly moisture-sensitive gas (31). It is utilized in esterification, ether formation, Friedel-Crafts alkylation and acylation, and Lewis acid-catalyzed Diels-Alder reactions. A more widely used, easy-to-handle and convenient liquid source of BF3 is boron trifluoride etherate [BF3-0(C2H5)2] (32). Its main usage as catalyst is in the direct esterification of all types of acids, rearrangements, aldol condensation, and Lewis acid-catalyzed Diels-Alder reactions. It is the most frequently used acid in epoxide ring opening and rearrangement (33). 

It is the chief constituent of the poisonous American wormseed oil and is found in amounts of up to 40% in oE of Cheno podium amhrosioides, although not found in other oils of the same type [52]. Ascaridole, as an inner peroxide, is found on chromatograms at a higher position than the hydroperoxides which have been repeatedly detected as intermediates during epoxide formation. Using n-hexane-diethyl ether (87 + 13), the three limonene peroxides can also be separated under standard conditions (hRf 22, 27 and 33) [85]. 

Crystallization of cis—1,4-polyisoprene from solution at -65 C has been carried out it is therefore possible that block copolymer preparation by epoxidation, bromination or some other reaction could be accomplished with lamellas of this polymer. Lamellar crystallization of cellulose, of amylose and of polyacrylic acid have been reported substitution reactions such as acetylation or ether formation with the hydroxyl groups and esterfication of the acid groups are possible reactions to carry out with lamellas of those polymers. The use of nonaqueous systems may be better suited to prevent swelling, and therefore, attack of the crystalline regions. It should also be possible to react poly(vinylalcohol) lamellas in suspension with acids or anhydrides to form vinyl-alcohol-vinyl ester block copolymers or with phosgene to obtain chloroformate groups which can undergo further reactions. 

Easily prepared from the appropriate monosaccharide, a glycal is an unsatu-rated sugar with a C1-C2 double bond. To ready it for use in potysaccharide synthesis, the primary -OH group of the glycal is first protected at its primary -OH group by formation of a silvl ether (Section 17.8) and at its two adjacent secondary - OH groups by formation of a cyclic carbonate ester. Then, the protected glycal is epoxidized. 

The C2-symmetric epoxide 23 (Scheme 7) reacts smoothly with carbon nucleophiles. For example, treatment of 23 with lithium dimethylcuprate proceeds with inversion of configuration, resulting in the formation of alcohol 28. An important consequence of the C2 symmetry of 23 is that the attack of the organometallic reagent upon either one of the two epoxide carbons produces the same product. After simultaneous hydrogenolysis of the two benzyl ethers in 28, protection of the 1,2-diol as an acetonide ring can be easily achieved by the use of 2,2-dimethoxypropane and camphor-sulfonic acid (CSA). It is necessary to briefly expose the crude product from the latter reaction to methanol and CSA so that the mixed acyclic ketal can be cleaved (see 29—>30). Oxidation of alcohol 30 with pyridinium chlorochromate (PCC) provides alde-... 

For 1,2-disubstituted epoxides, the regiochemical outcome of nucleophilic attack becomes less predictable. However, in the case of epoxy ethers chelation control can be used to deliver the nucleophile preferentially to the epoxide carbon away from the ether moiety. Thus, treatment of epoxy ether 61 with an imido(halo)metal complex, such as [Cr(N-t-Bu)Cl3(dme)], leads to the clean and high-yielding production of the chlorohydrin 64. The regioselectivity is rationalized in terms of initial formation of a chelated species (62), followed by attack at C-3 to form the more stable 5-membered metallacyclic alkoxide 63 <00SL677>. 

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