Ethers, aryl alkyl synthesis

Certain other sulfur-containing reagents also cleave methyl and other ethers see Hanes-sian, S. Guindon, Y. Tetrahedron Lett., 1980, 21, 2305 Williard, P.G. Fryhle, C.B. Tetrahedron Lett., 1980, 21, 3731 Node, M. Nishide, K. Fuji, K. Fujita, E. J. Org. Chem., 1980, 45, 4275. For cleavage with selenium-containing reagents, see Evers, M. Christiaens, L. Tetrahedron Lett., 1983, 24, 377. For a review of the cleavage of aryl alkyl ethers, see Tiecco, M. Synthesis, 1988, 749. 

Whereas carbenoid character is definitely present in metalated alkyl vinyl ethers, lithiated alkyl and aryl vinyl sulfides and thioesters, which are easily available by hydrogen-lithium exchange, do not display carbenoid-typical reactions . They rather behave like nucleophilic reagents, so that their discussion is beyond the scope of this overview despite their utility in synthesis The same appiies to various derivatives of enamines, deprotonated in the vinyiic a-nitrogen position - . 

Williamson synthesis of an aryl alkyl ether requires the Ar to be part of the nucleophile ArO and not the halide, since ArX does not readily undergo 5 2 displacements. Note that since ArOH is much more acidic than ROH, it is converted to ArO" by OH instead of by Na as required for ROH. 

A wide variety of amines, including aryl alkyl amines, alkyl amines, and amino alcohols have been resolved on a multi-ton scale (Scheme 7.10) [7]. This method has been used with methyl ethers. For example the racemic (l-methoxy)-2-propylamine (R,S 19) can be separated to give the (S)-20 which is required for the synthesis of a corn herbicide (21) and produced at 2500 t/y [7, 30] (Scheme 7.11). 

The so-called Williamson synthesis of ethers is by far the most important ether synthesis because of its versatility it can be used to make unsymmetrical ethers as well as symmetrical ethers, and aryl alkyl ethers as well as dialkyl ethers. These reactions involve the nucleophilic substitution of alkoxide ion or phenoxide ion for halide (equation 70).26°... 

Rather more conventional means were used to remove an alkyl silyl ether in the presence of an ary silyl ether in a synthesis of Dynemicin Here the task was simply accomplished with HF in acetonitrile [Scheme 4.56].92 Acidic conditions also prevailed in a synthesis of Doliculide wherein an alkyl tert-butyl ether, a tert-butyl ester and an N-fert-butoxycarbonyl group were cleaved simultaneously without challenge to the remaining aryl silyl ether [Scheme 4.57] ... 

Ruhland et al. synthesized polystyrene-bound selenium 72 and applied it to traceless solid-phase synthesis of a library of aryl alkyl ethers 73 (Scheme 48) [93]. 

The following methods are generally used for the laboratory preparation of ethers. (The Williamson synthesis is used for the preparation of aryl alkyl ethers industrially, as well.)... 

The Mitsunobu reaction proved to be useful for the synthesis of aryl alkyl ethers from alcohols and phenols. The method proceeds under mild conditions and tolerates many functional groups with inversion of configuration, as exemplified by the reactions of lactate and ewrfo-5-norbornen-2-ol (equations 4 and Neighboring group participation,... 

When an organolithium compound reacts with an organic halide the product is usually a hydrocarbon, reaction being analogous to a Wurtz-Fittig synthesis. However, the action of alkyl- or aryl-lithiums replaces the halogen by lithium in several halogenated heterocycles, aromatic ethers, and alkyl... 

Selective Dealkylations of Aryl Alkyl Ethers, Thioethers and Selenoethers Tiecco. M. Synthesis. 1988, 749. 

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