Cyclic ethers acid catalysis

The cyclization of ort/zo-allyl phenols was reported by Murahashi in the late 1970s. The reaction of the 2-(2-cyclohexenyl)phenol (Equation 16.110) was one of the early examples of Wacker-type reactions with alcohol nucleophiles and has been re-investigated in more recent years with chiral catalysts. Intramolecular reactions of alkene-ols and alkenoic acids form cyclic ethers and lactones. These reactions were reported by Larock and by Annby, Andersson, and co-workers, and examples are shown in Equations 16.111 and 16.112. °° ° The use of DMSO as solvent was important to form the lactone products. More recently, reactions with alcohols were reported by Stoltz to form cyclic ethers by the use of pyridine and related ligands in toluene solvent. - The type of ligand, whether an additive or the solvent, is crucial to the development of these oxidative processes. However, the features of these ligands that lead to catalysis are not well understood at this time. 

Alko xy ally 1)stannane aldehydes (57) can cyclize either thermally or with Lewis or protic acid catalysis to give cyclic ethers (58).85 The interrelationship of the reactant and product stereochemistries has been investigated, as have the methods used to promote the reaction. For both thermal and proton-promoted reactions, [(Z)-57 gave (cis-58), and [(E)-57] gave trans-58), whereas trans-58) was the predominant or exclusive product of Lewis acid mediation, regardless of the double bond geometry of... 

Acetophenones, aliphatic and cyclic ketones were a-acetoxylated by DIB in acetic acid-acetic anhydride, in the presence of sulphuric acid, in moderate yield some / -diketones were similarly acetoxylated at the methylene carbon. The more reactive trimethylsilyl ethers reacted at room temperature without acid catalysis, with retention of their silyl group the products came either from substitution of the vinylic hydrogen or from bis acetoxylation of the double bond. 

Alkenylsilanes and -stannanes, and arylsilanes and -stannanes are useful reagents for transfer of an sp -carbon unit to electrophiles under titanium catalysis. Epoxides are opened by TiCE to generate cationic carbon, which is successfully trapped with bis(trimethylsilyl)propene as an aUcenylsilane (Eq. 122) [305]. Other Lewis acids, for example ZnCla, SnCU, and BF3 OEt2, proved less satisfactory. Cyclic epoxides such as cyclopentene and cyclohexene oxides gave poorer yields. An intramolecular version of this reaction proceeded differently (Eq. 123) [305]. Eqs (124) and (125) illustrate diastereoselective alkenylation and arylation of (A,0)-acetals that take advantage of the intramolecular delivery of alkenyl and aryl groups [306], Cyclic ethers... 

The homologation of ketones by the addition of diazoalkanes complements the Tiffeneau-Demjanov rearrangement. Epoxide formation is a side reaction which can be minimized if polar aprotic solvents are avoided (Scheme 7). Rearrangement i.e. homologation) is maximized in ether solvents or by Lewis acid catalysis. The reaction is most effective in the ring expansion of cyclic ketones. 

In some cases the presence of both redox and Bransted acid sites can be an asset as it can provide the possibility of performing bifiinctional catalysis. For example, Ti-BEA and Ti-MCM-41 (see later) catalyzed the epoxidation of linalool with TBHP, with in-situ acid-catalyzed rearrangement to a mixture of cyclic ethers (Reaction 14) [S6]. 

A-Tosyl-aziridines (and A-tosyl-azetidines) react with cyclic enol ethers and enamides, under Lewis acid catalysis to give synthetically useful bicycles. ... 

Some electron-rich olefins, such as enol ethers 170, react directly with 32 under mild conditions with Lewis acid catalysis. The first product of the reaction results from addition of the S-Cl bond to the olefin, the sulfur atom being attached to the carbon / to the oxygen and the chlorine in the a-position. If the / -carbon carries a hydrogen atom, elimination of HCl can be effected with mild bases such as triethylamine to regenerate a double bond. The reaction works with both cyclic and acyclic enol ethers, the latter case giving ( ) (Z)-mrxtures of products 171 (Equation 13) <2000JHC583>. 

Most attempted conversions of (25) to (26) by conventional acid catalysis (e.g. HCOOH in pentane, AICI3 in ether or BF3 Et20 in CH2CI2) lead predominantly to mixtures of the alkenes rather than the desired (26) (<30%) [42]. Under these conditions, deprotonation of the cyclic carbocation species takes precedence over return of the OH-group or - if formed - (26) is unstable under the reaction conditions. A rationalization of the successful conversion by EGA catalysis in acetone is the trapping of the cy-clized carbocation by acetone giving (27), which is hydrolyzed to (26) (52%, 0% de). Scheme 16. Other solvents gave none of... 

Among the industrially relevant cyclic ethers tetrahydrojuran (THF) is by far the most important. THF is produced by condensation of 1,4-butandiol that is obtained from several feedstock basis (acetylene, propene, butadiene, and butane, see Scheme 5.3.4). 1,4-Dioxane is obtained by condensation of diethylene glycol that itself is obtained by the addition of water to ethylene oxide. The reaction is catalyzed by sulfuric acid (homogeneous catalysis) or by acidic ion-exchange resins (heterogeneous catalysis) and proceeds at about 160 °C with continuous distillative removal of water. 

The main stereoselective MBFTs for the synthesis of spirocyclic acetals or aminals involve the activation of a C-C triple bond to form an intermediate cyclic enol ether. The method disclosed above for the synthesis of a-heteroatom-substituted spirocen-ter (see Section 9.3.3, Scheme 9.18) [34] was next extended by the same authors to the synthesis of spiroacetals. They simply used salicyladehyde as starting aldehyde, but the transformation was not diastereoselective anymore [43]. This problem of stereoselectivity was recently solved by Gong and coworkers, who employed a gold(I)/chiral Brpnsted acid catalysis to do so [44], The chroman spiroacetals were obtained in excellent yields (67-97%) and with high stereoselectivities (up to 95% ee, up to 25 1 dr) (Scheme 9.24). This reaction resulted in the formation of three new single bonds and two stereogenic centers. 

Certain other metal ions also exhibit catalysis in aqueous solution. Two important criteria are rate of ligand exchange and the acidity of the metal hydrate. Metal hydrates that are too acidic lead to hydrolysis of the silyl enol ether, whereas slow exchange limits the ability of catalysis to compete with other processes. Indium(III) chloride is a borderline catalysts by these criteria, but nevertheless is effective. The optimum solvent is 95 5 isopropanol-water. Under these conditions, the reaction is syn selective, suggesting a cyclic TS.63... 

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