Ethyl vinyl ether nucleophilicity

Simple alkyl radicals such as methyl are considered to be nonnucleophilic. Methyl radicals are somewhat more reactive toward alkenes bearing electron-withdrawing substituents than towards those with electron-releasing substituents. However, much of this effect can be attributed to the stabilizing effect that these substiments have on the product radical. There is a strong correlation of reaction rate with the overall exothermicity of the reaction. Hydroxymethyl and 2-hydroxy-2-propyl radicals show nucleophilic character. The hydroxymethyl radical shows a slightly enhanced reactivity toward acrylonitrile and acrolein, but a sharply decreased reactivity toward ethyl vinyl ether. Table 12.9 gives some of the reactivity data. 

In the synthesis of carpamic acid (98), Mitsutaka and Ogawa have used 1,2-dihydropyridine as a starting material [80H(14)169]. Photooxygenation of dihydropyridine 8h afforded enr/o-peroxide 96. Subsequent stereoselective nucleophilic reaction of 96 with ethyl vinyl ether in the presence of tin chloride gave tetrahydropyridinol 97, which was then converted into carpamic acid (98) in six more steps. 

Aryl cation chemistry allows a double functionalization of vinyl ethers in a three-component reaction, as depicted in Scheme 3.30. In this case, a 3-arylacetal (e.g., 47) was synthesized after the initial addition of the 4-hydroxyphenyl cation onto ethyl vinyl ether, followed by trapping with the nucleophilic solvent MeOH [77]. For related arylation reactions, see Chapter 10. 

On constant current electrolysis (0.27 mAcm +180-600 mV V5. SCE) in AC2O containing ethyl vinyl ether, 4,5-dimethoxy-2-methylphenol (108) was converted to two cyclohexa-2,4-dienones 109 and 110 and cyclohexa-2,5-dienone 111, in 29, 18 and 8% yields, respectively (Scheme 20). The product 110 is formed by nucleophilic substitution at the C-6 position followed by acetal formation with EtOH molecule generated initially from the ethyl vinyl ether while the C-4 position is attacked by ethyl vinyl ether to yield 111. 

The relevance of the carbocationic mechanism was also demonstrated for the polymerization of ethyl vinyl ether by end-group analysis following termination with aqueous methanol. An aldehydic resonance (d 9.8) was observed in the H NMR spectrum of the resulting polymer, the aldehyde functionality arising from hydrolysis of the acetal formed via nucleophilic attack by methanol on the active site of the growing polymer (eqs 17 and 18). 

Conjugate nucleophilic addition of methyl, vinyl, allyl, and malonate groups to l-(2-indolyl)but-2-enecarbonitrile has been effected with a range of organometallic carbanions, for example, the lithium derivative of ethyl vinyl ether gives the product (390), which can be cyclized to a pyrrolof 1,2-ajindole (391) (Scheme 130) <9ITL7237>. 

Arynes react readily with simple alkenes to give either benzocyclobutenes or substituted benzenes (Scheme 7.31). The formation of benzocyclobutenes by [2+2] cycloaddition reaction of the aryne to the alkene proceeds best for strained and electron-rich carbon-carbon (C=C) double bonds. For example, dicyclopentadiene reacts to give the ex o-isomer of the corresponding four-membered ring in good yield. The addition to cyanoethene (acrylonitrile) and the reaction with the electron-rich ethoxyethene (ethyl vinyl ether) gives the cyano- and ethoxy-benzocyclobutenes in 20% and 40% yields, respectively. The latter reaction almost certainly involves nucleophilic addition of the enol ether to the electrophilic aryne followed by coUapse... 

A three-component coupling involving three alkenes was employed using a stoichiometric amount of palladium to generate a bicyclic acetal 6.91, which could be converted to an epimer of the prostaglandin, PGF2 (Scheme 6.31). The three-component coupling involves nucleophilic attack of the alcohol 6.89 onto an ethyl vinyl ether-palladium complex 6.93, intramolecular alkene insertion, intermolecular insertion of... 

Tetracyanobutanal acetal (216) (readily obtained from tetracyanoethylene, ethyl vinyl ether, and ethanol) has been reported to be converted into 2-aminopyridine derivative (219) in the presence of pyridine. On the basis of several experiments, the proposed mechanism involves the Michael reaction of (216) via (217) with diene (218), generated by the elimination of hydrogen cyanide and ethanol from (216), followed by double intramolecular nucleophilic additions to the cyano groups. ... 

Table 2 also indicates that the nucleophiles effective for vinyl ethers are relatively mild, when compared with those for isobutene (cf., Section V.B.2). In fact, stronger bases lead to inhibition or severe retardation of polymerization [36,64] ketones aldehydes, amides, acid anhydrides, dimethyl sulfoxide (retardation) alcohols, aliphatic amines, pyridine (inhibition). The choice of nucleophiles is determined by their Lewis basicity (as measured by pKb, etc. [64,103]), and this factor determines the effic-tive concentrations of the nucleophiles. For example, the required amounts of esters and ethers decrease in the order of increasing basicity (i.e., a stronger base is more effective and therefore less is needed) [101,103] tetrahydrofuran < 1,4-dioxane ethyl acetate < diethyl ether. On the other hand, for amines not only basicity but also steric factors play an important role [142] thus, unsubstituted pyridine is an inhibitor, while 2,5-dimethylpyridine is an effective nucleophile for controlled/living polymerization, although the latter is more Lewis basic. 

These nucleophiles are much stronger than those used for vinyl ethers (Section V. A.4 Table 2. A), and their concentrations are usually lower than that of the Lewis acid activator, in sharp contrast to the cases for vinyl ethers where the nucleophiles are usually in a large excess over the Lewis acid (the concentrations depend upon the Lewis acidity, however). It is reported, for example, that the concentration of ethyl acetate should be below the TiCl4 concentration, otherwise no polymerization occurs [91]. 

Vinylic ether-containing Claisen rearrangement substrates may be generated using syn-elimination reactions of sulfoxides, selenoxides, and selenones. 2-(Arylsulfinyl)ethyl ethers are particularly useful substrates in these reactions because of their ready availability by nucleophilic addition of allylic alcohols to commercially available phenylsulfinylethene. Scheme 13.27 shows a typical synthetic context for this chemistry, involving the stereospecific introduction of quaternary centers from easily accessed allylic alcohol precursors." ... 

---