Ethers, vinyl reaction with radicals

Radical cyclization of polyfunctional 5-hexenyl halides mediated by Et2Zn and catalyzed by nickel or palladium salts has been demonstrated to produce stereoselectively polyfunctional 5-membered carbo- and heterocycles [56, 57]. Based on this strategy a formal synthesis of methylenolactocin (11) was achieved (Scheme 20). The acetal 130, readily being built up by asymmetric alkylation of aldehyde 127 followed by reaction with butyl vinyl ether and NBS, served as the key intermediate for the construction of the lactone ring. Nickel(II)-catalyzed carbometallation was initiated with diethylzinc to yield exclusively the frans-disubstituted lactol 132, which could be oxidized directly by air to 134. Final oxidation under more forcing conditions then yielded the lactone (-)-75 as a known intermediate in the synthesis of (-)-methylenolactocin (11) [47aj. 

An investigation into the initiation mechanism of copolymerization of ethyl vinyl ether and acrylonitrile by /-butoxyl radicals lias shown that the reaction between the two monomers competes successfully with radical trapping by the nitroxide radical trap (5).37 The /-butoxyl radicals react 3-6 times faster with ethyl vinyl ether than acrylonitrile the authors proposed that this is due to selective interaction of one monomer with the radical species rather than a solvent polarity effect. 

An /V-allylaminium cation radical undergoes an addition-cyclization reaction with vinyl ethers in the presence of t-BuSH to give 3-alkoxy-4-methylpyrrolidines 72 (Scheme 23) in fair to good yields (90TL1675). In addition to EVE, 2,3-dihydrofuran and 3,4-dihydro-(2//)pyran also undergo reactions to give bicycles 73 and 74, respectively, in reasonable yield. 

Addition reactions with Mode B are not popular, but are occasionally useful. Eq. 4.7 indicates the reaction of ethyl bromoacetate and sugar vinyl ether with Bu3SnH initiated by AIBN. The ethyl acetate radical is electrophilic and it reacts with electron-rich sugar vinyl ether through SOMO-HOMO orbital interaction to form a ribosyl anomeric radical, as shown below. Then, the formed ribosyl anomeric radical abstracts... 

A diastereoselective formal addition of a 7ra i-2-(phenylthio)vmyl moiety to a-hydroxyhydrazones through a radical pathway is shown in Scheme 2.29. To overcome the lack of a viable intermolecular vinyl radical addition to C=N double bonds, not to mention a reaction proceeding with stereocontrol, this procedure employs a temporary silicon tether, which is used to hold the alkyne unit in place so that the vinyl radical addition could proceed intramolecularly. Thus, intermolecular addition of PhS" to the alkyne moiety in the chiral alkyne 161 leads to vinyl radical 163, which cyclizes in a 5-exo fashion, according to the Beckwith-Houk predictions, to give aminyl radical 164 with an a 7z-arrangement between the ether and the amino group. Radical reduction and removal of the silicon tether without prior isolation of the end product of the radical cyclization cascade, 165, yields the a-amino alcohol 162. This strategy, which could also be applied to the diastereoselective synthesis of polyhydroxylated amines (not shown), can be considered as synthetic equivalent of an acetaldehyde Mannich reaction with acyclic stereocontrol. 

Owing to its radical nature, this addition reaction can take place with different kind of alkenes. This is examplified in Scheme 12 in which the reaction products 74,75, and 76 illustrate the regioselectivity and the chemoselectivity of the addition reaction with different substrates such as enol ethers, a, -unsaturated esters and a, -unsaturated vinyl esters. 

The ether oxygen is a Lewis base (electron donor), and polymerization of vinyl and cyclic ethers can be initiated by reaction with an ion pair comprising an acidic cation and a weakly nucleophilic base. These monomers do not polymerize by free-radical or anionic processes. Thio ethers behave similarly. 

Scheme 33. Kinetic studies of the cation radical Diels-Alder reactions of aryl vinyl sulfides with cyclopentadiene and of aryl propenyl ethers with 2,3-dimethyl 1,3-butadiene. In both solvents, both extended reaction series have rates which correlate excellently with the Hammett a parameters and poorly with the Hammett-Brown o-+ values. The preference is statistically significant at or above the 95 % confidence level.

There seems little doubt that in radiation induced polymerizations the reactive entity is a free cation (vinyl ethers are not susceptible to free radical or anionic polymerization). The dielectric constant of bulk isobutyl vinyl ether is low (<4) and very little solvation of cations is likely. Under these circumstances, therefore, the charge density of the active centre is likely to be a maximum and hence, also, the bimolecular rate coefficient for reaction with monomer. These data can, therefore, be regarded as a measure of the reactivity of a non-solvated or naked free ion and bear out the high reactivity predicted some years ago [110, 111]. The experimental results from initiation by stable carbonium ion salts are approximately one order of magnitude lower than those from 7-ray studies, but nevertheless still represent extremely high reactivity. In the latter work the dielectric constant of the solvent is much higher (CHjClj, e 10, 0°C) and considerable solvation of the active centre must be anticipated. As a result the charge density of the free cation will be reduced, and hence the lower value of fep represents the reactivity of a solvated free ion rather than a naked one. Confirmation of the apparent free ion nature of these polymerizations is afforded by the data on the ion pair dissociation constant,, of the salts used for initiation, and, more importantly, the invariance, within experimental error, of ftp with the counter-ion used (SbCl or BF4). Overall effects of solvent polarity will be considered shortly in more detail. 

Formation of a cation radical of the diene may catalyze Diels-Alder reactions with certain dienophiles thus oxidation of substituted vinylindoles to the cation radical in the presence of a push-pull dienophile may form different heterocyclic compounds by the Diels-Alder reaction, for instance pyrido[l,2i7]indoles from vinylindoles and yS-enamino-esters [33]. Similarly, anodic oxidation in MeCN of certain oxazolidines in presence of vinyl ether leads to derivatives of oxazepines in a catalytic reaction in which the ring-opened radical cation of the oxazolidine adds to the vinyl ether and the radical cation of the resulting oxazepine oxidizes the oxazolidine [34]. 

Functionally substituted benzylic, allylic, and vinylic compounds containing alkoxides, esters, ethers, nitriles, or amides can be reacted with halosilanes under Barbier conditions using HMPT to yield C- and O-silylated products, 1,2- or 1,4-addition products, as well as reductive dimers. Radical and anionic intermediates are postulated, based on SET reactions from the metal, and multiple silated species can be obtained. The use of the TMSCl-Mg-HMPT system has been extensively investigated by Galas group [85] at the University of Bordeaux, and their work has greatly advanced the science of the Barbier reaction with silanes. 

Thiault G., A. MeUouki, G. Le Bras Rate constants for the OH radical reaction with n-propyl, n-butyl, iso-butyl and tert-butyl vinyl ethers to be submitted (2005). 

With unsymmetrical alkenes, there are two regioisomeric meta adducts,1154 1160 1161 which are easily understood as the consequences of bond formation from the diradical intermediates 8.138 and 8.141, with the isolated radical centre forming a bond to either end of the allyl radical with little selectivity stemming from the presence of the substituent on the alkene. The low degree of selectivity is equally accommodated by a concerted reaction in which there is no intermediate. The main effect of having an electron-donating group, as in the reaction with ethyl vinyl ether 8.76, is that the ortho adduct 8.131 is the major product. The meta adducts 8.142-8.145 (R = OEt) are minor products (ortho.meta 65 35). With the rather less effective donor substituent, as in the reaction with vinyl acetate, the meta adducts 8.142-8.145 (R = OAc) are the major products (meta ortho 88 12). They show some selectivity in favour of the endo adducts (64 36 for R = OEt), and the major product 8.142... 

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