Tertiary alcohols ether synthesis from

Based on the elimination reaction, Pericas and coauthors" have developed a method for the synthesis of acetylenic ethers, derived from tertiary alcohols with a bulky alkyl group such as r -butyl and adamantyl. The key step in this synthesis is the dehydrobromination of l-bromo-2-alkoxyethylene 67 with sodium amide in ammonia or lithium diisopropylamide in a hexane-THF solution (equation 39)". ... 

Two approaches for the synthesis of allyl(alkyl)- and allyl(aryl)tin halides are thermolysis of halo(alkyl)tin ethers derived from tertiary homoallylic alcohols, and transmetalation of other allylstannanes. For example, dibutyl(-2-propenyl)tin chloride has been prepared by healing dibutyl(di-2-propenyl)stannane with dibutyltin dichloride42, and by thermolysis of mixtures of 2,3-dimethyl-5-hexen-3-ol or 2-methyl-4-penten-2-ol and tetrabutyl-l,3-dichlorodistannox-ane39. Alternatively dibutyltin dichloride and (dibutyl)(dimethoxy)tin were mixed to provide (dibutyl)(methoxy)tin chloride which was heated with 2,2,3-trimethyl-5-hexen-3-ol40. 

Acidic clays are widely applied in the dehydration of alcohols [38]. Although similar to zeolites in their capacity to induce the formation of both alkenes and ethers, selective alkene synthesis is possible. Various layered materials (clays, ion-exchanged montmorillonite, pillared layered clays) are very active and, in general, selective in transforming primary, secondary, and tertiary aliphatic alcohols to 1-alkenes [39-43]. Al -exchanged montmorillonite, however, induces ether formation from primary alcohols and 2-propanol [41]. Substituted 1-phenyl-1-ethanols yield the corresponding styrene derivatives at high temperature (653-673 K) [44]. 

A variant of the Williamson ether synthesis uses thallium alkoxides. The higher reactivity of these can be of advantage in the synthesis of ethers from diols, triols and hydroxy carboxylic acids, as well as from secondary and tertiary alcohols on the other hand however thallium compounds are highly toxic. 

In comparison to the N- and S-counterparts, alkoxides possess lower nucleophilicity. Therefore, the reductive elimination process to form the C—O bond is much slower than those to form C— N and C—S bonds [103]. Palucki, Wolfe and Buchwald developed the first intramolecular Pd-catalyzed synthesis of cyclic aryl ethers from o-haloaryl-substituted alcohols [104]. For example, 3-(2-bromophenyl)-2-methyl-2-butanol (91) was converted to 2,2-dimethylchroman (92) under the agency of catalytic Pd(OAc)2 in the presence (S)-(-)-2,2 -bis(di-p-tolylphosphino)-l,r-binaphthyl (Tol-BINAP) as the ligand and K2CO3 as the base. The method worked well for the tertiary alcohols, moderately weE for cychc secondary alcohols, but not for acyclic secondary alcohols. 

Thus, a wide variety of vinyl ethers could be synthesized using this method (Scheme 10.5). This catalyhc vinylation system was found to be applicable to the synthesis of vinyl ethers from secondary and tertiary alcohols. No deuterium was introduced into the resulhng phenyl vinyl ether when phenol-d was allowed to... 

Essentially the same route is followed for the synthesis of the triphenylethylene nitromifene (8-5). The sequence starts with Friedel-Crafts acylation of the alkylation product (8-1) from phenol and 1,2-dibromoethane with the acid chloride from anisic acid (8-2). The displacement of bromine in the product (8-3) with pyrrolidine leads to the formation of the basic ether and thus (8-4). Condensation of that product with benzylmagnesium bromide gives the tertiary alcohol (8-5). This product is then treated with a mixture of nitric and acetic acids. The dehydration products from the first step almost certainly consist of a mixture of the E and Z isomers for the same reasons advanced above. The olefin undergoes nitration under reaction conditions to lead to nitromifene (8-6) as a mixture of isomers [8] the separated compounds are reported to show surprisingly equivalent agonist/antagonist activities. 

Phenylselenoetherification (8, 26-28). This cyclization has been described in detail.6 The 16 examples reported indicate that the reaction is applicable to unsaturated primary, secondary, and tertiary alcohols as well as to phenols. The most important use is for synthesis of allylic ethers by syn-selenoxide elimination, which proceeds selectively away from the oxygen. The value of this methodology for synthesis of natural products is illustrated by a synthesis of a muscarine analog (1), outlined in equation (I). 

Doyle and co-workers have employed Rh2(pfb)4 as a highly selective catalyst for the room temperature synthesis of silyl ethers from alcohols and triethylsilane.159 The selectivity of the catalyst is demonstrated by reactions of olefinic alcohols, in which hydrosilylation is not competitive with silane alcoholysis when equimolar amounts of silane and alcohol are employed. High yields (>85%) of triethylsilyl ethers are obtained from reactions of alcohols such as benzyl alcohol, 1-octanol, 3-buten-l-ol, cholesterol, and phenol. Tertiary alcohols are not active in this system. 

Synthesis ofkarahanaenaue. The ionic reaction of NBS in CCI4 at room temperature with a y-ethylcnic tertiary alcohol leads to an -bromotetrahydrofurane. The reaction has been used in a convenient synthesis of karahanaenone (4), a constituent of hop oil, from linalool (1). Thus reaction of (1) with NBS affords 2-mcthyl-2-vinyl-5-(l-bromo-l-methylethyl)tetrahydrofurane (2) in 85% yield. Dehydrohalogena-tion of (2) with collidine at 110 leads to the allyl vinyl ether (3), which immediately... 

The Williamson reaction, discovered in 1850, is still the best general method for the preparation of unsymmetrical or symmetrical ethers.The reaction can also be carried out with aromatic R, although C-alkylation is sometimes a side reaction (see p. 515). The normal method involves treatment of the halide with alkoxide or aroxide ion prepared from an alcohol or phenol, although methylation using dimethyl carbonate has been reported. It is also possible to mix the halide and alcohol or phenol directly with CS2CO3 in acetonitrile, or with solid KOH in Me2SO. The reaction can also be carried out in a dry medium,on zeolite-or neat or in solvents using microwave irradiation. Williamson ether synthesis in ionic liquids has also been reported. The reaction is not successful for tertiary R (because of elimination), and low yields are often obtained with secondary R. Mono-ethers can be formed from diols and alkyl halides. Many other... 

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