Acyclic ethers, preparation with

Activation energy, iimobilized catalyst kinetics, 76 Acyclic ethers, preparation with Nafion, 51-52... 

Arguably the most challenging aspect for the preparation of 1 was construction of the unsymmetrically substituted sec-sec chiral bis(trifluoromethyl)benzylic ether functionality with careful control of the relative and absolute stereochemistry [21], The original chemistry route to ether intermediate 18 involved an unselective etherification of chiral alcohol 10 with racemic imidate 17 and separation of a nearly 1 1 mixture of diastereomers, as shown in Scheme 7.3. Carbon-oxygen single bond forming reactions leading directly to chiral acyclic sec-sec ethers are particularly rare since known reactions are typically nonstereospecific. While notable exceptions have surfaced [22], each method provides ethers with particular substitution patterns which are not broadly applicable. 

Strategies for preparing mixed, acyclic acetals on insoluble supports include the oxidative haloalkoxylation of support-bound enol ethers (Entry 6, Table 6.1) and the acid-catalyzed reaction of alcohols with resin-bound enol ethers [627]. Alternatively, resin-bound a-chloro ethers can be converted to mixed acetals by reaction with alcohols or phenols in the presence of strong bases (KO/Bu, HOfBu, DMF, 5 h) [550,628]. Polystyrene-bound a-(phenylseleno)ethers react with aliphatic alcohols under slightly acidic conditions (NIS, TfOH, DCM/dioxane (1 1), 0°C to 20 °C, 1 h) to yield mixed, acyclic acetals [628],... 

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. 

Most acyclic ethers can be prepared using Williamson synthesis. This involves reacting an alkoxide with a haloalkane. As stated previously, alkoxides are created by reacting an alcohol with metallic sodium or potassium. 

Shibasaki and co-workers used a ring-closing metathesis approach to prepare a number of five-, six-, and seven-membered rings from electron-deficient olefins. Treatment of acyclic enol ether 18 with 7 mol % of 3 in refluxing benzene provided the corresponding cyclic enol ether 19 in 94% yield. Deprotection of the silyl ether 19 (not shown) resulted in the corresponding cyclic ketone, a valuable synthetic intermediate in natural products synthesis and a number of industrial processes. The authors reported additional examples of the synthesis of five-membered ring carbocycles as part of this study. 

Perfluoroallyl fluorosulfate is prepared by the treatment oiperfluoropropene with sulfur tnoxide m the presence of boron catalysts [2, 3, 4, 5, 6, 7] (equation 2) Perfluoroisopropyl allyl ether reacts similarly to give 58% polyfluoroallyl fluorosulfate in a cis/trans ratio of 6 4 [S] Sultones are the exclusive products without catalyst. Polyfluoroolefins such as 2-hydropentafluoropropylene [9], (2,3-dichloropropyl)tri-fluoroethylene [70], perfluoropropene [2, i], perfluoroisopropyl alkenyl ethers [S], and acyclic polyfluoroallyl ethers [77] undergo sulfur trioxidation to regioselectively produce the corresponding P-sultones in high yield... 

Cyclic and acyclic silyl enol ethers can be nitrated with tetranitromethane to give ct-nitro ketones in 64-96% yield fEqs. 2.42 and 2.43. " The mechanism involves the electron transfer from the silyl enol ether to tetranitromethane. A fast homolydc conphng of the resultant cadon radical of silyl enol ether with NO leads tn ct-nitro ketones. Tetranitromethane is a neutral reagent it is commercially available or readdy prepared. " ... 

During the past 2 years several research groups have published research that either uses or expands upon Crowe s acyclic cross-metathesis chemistry. The first reported application of this chemistry was in the synthesis of frans-disubstitut-ed homoallylic alcohols [30]. Cross-metathesis of styrenes with homoallylic silyl ethers 15, prepared via asymmetric allylboration and subsequent alcohol protection, gave the desired trans cross-metathesis products in moderate to good yields (Eq. 15). 

Related catalytic enantioselective processes It is worthy of note that the powerful Ti-catalyzed asymmetric epoxidation procedure of Sharpless [27] is often used in the preparation of optically pure acyclic allylic alcohols through the catalytic kinetic resolution of easily accessible racemic mixtures [28]. When the catalytic epoxidation is applied to cyclic allylic substrates, reaction rates are retarded and lower levels of enantioselectivity are observed. Ru-catalyzed asymmetric hydrogenation has been employed by Noyori to effect the resolution of five- and six-membered allylic carbinols [29] in this instance, as with the Ti-catalyzed procedure, the presence of an unprotected hydroxyl function is required. Perhaps the most efficient general procedure for the enantioselective synthesis of this class of cyclic allylic ethers is that recently developed by Trost and co-workers, involving Pd-catalyzed asymmetric additions of alkoxides to allylic esters [30]. 

The reaction is applicable to acyclic and cyclic enol ethers and to various (3-dicarbonyl compounds, but fails with silyl enol ethers and simple 1,2-disubstituted alkenes. When applicable, this route to furans is useful because the yields and regioselectivity are consistently satisfactory. The paper includes a preparation of the reagent by reaction of Mn(NO,)3 with Ac20 at 100° to give Mn,0(0Ac)7 H0Ac in 60% yield. 

A semiempirical AMI study of the inverse-electron-demand Diels-Alder reaction of 4-substituted 6-nitrobenzofurans with enol ethers and enamines favours a stepwise mechanism involving short-lived diradical intermediates. The inverse-electron-demand intermolecular Diels-Alder reactions of 3,6-bis(trifluoromethyl)-l,2,4,5-tetra-zine with acyclic and cyclic dienophiles followed by the elimination of N2 produce 4,5-dihydropyridazines, which cycloadd further to yield cage compounds. The preparation of jS-carbolines (90) via an intramolecular inverse-electron-demand Diels-Alder... 

A -Unsubstituted 1,2,4-diazaphospholes (4) undergo A -alkylation by reaction with alkyl vinyl ether, sulfur ylides, and diazo compounds <95HAC403>. They react with acyl chlorides in a 2 1 molar ratio to give a mixture of the A -acylated diazaphosphole and the diazaphosphole hydrochloride. Preparative A -acyclation is achieved in presence of a tertiary amine. Sulfonyl chlorides and phosphorus trichloride also give A -substitution reactions (Scheme 2) <87TH 422-01 >. 

Using diethyl ether as solvent, SAMP/RAMP-hydrazones of acyclic ketones are alkylated in good chemical yield and generally enantiomeric purities of > 90 % are achieved (see Table 3). Most prominent is the preparation of the alarm pheromone of the ant, ( + )-(5T)-4-methyl-3-hep-tanone, which proceeds with practically complete asymmetric induction5,38. Lower enantiomeric excesses (10-30%) are obtained in the alkylation of ketones which contain a phenyl substituent at the alkylated carbon3,8. 

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