Vinyl allyl ether isomerizations

Vinyl allyl ethers and allyl aryl ethers are converted by heating to y,6-unsaturated carbonyl compounds and allyl phenols, respectively. The two groups of reactions are mechanistically related, and are referred to as Claisen rearrangements. Claisen rearrangements of allyl aryl ethers have been reviewed and their kinetics are discussed in Chapter 3 Volume 13 of this series. The present discussion is limited to thermal isomerizations of vinyl allyl ethers. 

When a vinyl allyl ether is isomerized, a a bond forms between the /3 carbon of the vinyl group and the y carbon of the allyl group. Simultaneously, tt bonds are formed between the vinyl a carbon and oxygen and between the a and p carbons of the allyl system, and the original tt bonds become t bonds, viz- 

The reaction is highly stereospecific and is always accompanied by inversion of the structure of the allyl group. This inversion is experimentally detectable when the a carbon or y carbon bears an alkyl substituent and is detectable in the case of allyl vinyl ether itself if the a or y carbons of the allyl group are labeled with (ref. 257). That the a carbon of the vinyl group of the ether becomes the carbonyl carbon of the product is demonstrated by the isomerization of isopropenyl allyl ether to hex-5-ene-2-one, and by the isomerization of CH2=CDOO H to CH2=CHCH2CH2CD02S7. 

The kinetics of isomerizations of vinyl allyl ethers have been studied in the gas phase, in solution, and in the neat liquid ether. In the gas phase, isomerization rate is independent of pressure down to about 1 torr, below which the rate diminishes with decreasing pressure in the manner characteristic of uni-molecular reactions . The rate of isomerization is not influenced significantly by glass surfaces, but is faster in solution in either non-polar or moderately polar solvents than in the gas phase. Reactivity is increased by methyl substitution of either the vinyl or the allyl group of the ether. All of the isomerizations thus far studied have negative entropies of activation, with values ranging from —8 to —13eu, Isomerization of vinyl allyl ether (neat liquid) at 130°C exhibits a volume of activation of — 18 cm. mole . Published kinetic data are summarized in Table 3. 

The first-order kinetics, lack of dependence of rate upon pressure in the gas phase above 1 torr, absence of catalysis, and stereospecificity all show that vinyl allyl ether isomerizations are unimolecular reactions. The effects of substrate structure and solvents on reactivity indicate that the rate-limiting transition state does not resemble an ion pair. Methyl substituents on the a and y carbons of the allylic group increase reactivity by only about 10- and 2.5-fold respectively, which is very much less than substituent effects on ionic allylic reactions. While the isomerization of vinyl a-methylallyl ether is about ten times faster in organic solvents than in the vapor phase, the solvent effect is small and does not correlate with solvent polarity. 

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With the results thus far obtained we can now make a detailed formulation of a simple chemical reaction, isomerization. Some examples of chemical isomerizations which have been studied in the gas phase and found to follow homogeneous, first-order rates are certain cis-trans isomerizations of olefins and some allylic rearrangements, such as the rearrangement of vinyl allyl ether, CH2=CH—O—CH2—CH=CIl2, to allyl acetaldehyde, CIl2=CH—CH2—CH2—Clio. 

In contrast to these cases, the isomerization of vinyl allyl ether to n-pentaldehyde-ene-4 (Table XI.3), which may be pictured as going through the hypothetical six-membered ring complex shown in brackets, ... 

Unimolecular reactions that take place by way of cyclic transition states typically have negative entropies of activation because of the loss of rotational degrees of freedom with the introduction of a high degree of order in the activated complex. Thus, thermal isomerization of vinyl allyl ether to 4-pentenal has = —8 cal/mol... 

Isomerization of the double bond in allylic alcohols may result in aldehydes or ketones (I07a). The reaction can have synthetic value (8bJ3c). If isomerization is desired, palladium is probably the preferred catalyst, operated best under hydrogen-poor conditions (/47fl). Allylic ethers can be converted to alcohols by isomerization with (Ph3P)3RhCl at pH 2 to the vinyl ether, which undergoes hydrolysis (36a). 

The isomerization of allyl ethers and allyl acetals to vinyl ethers or vinyl acetals, respectively, has found many applications in organic synthesis (Equation (17)). Various transition metal catalysts have been reported in the literature for the isomerization of allyl ethers and allyl acetals. 

Ru(H20)6], which is a precursor of ROM polymerization of cyclic dienes has also been found to possess good alkene isomerization activity [1], Among others it catalyzed the isomerization of allylphenyl ether to a vinylphenyl ether (Scheme 9.1) at room temperature. Allyl ethers are stable to acids and bases, while vinyl ethers are easily cleaved in acidic solutions. Therefore this isomerization gives a mild method for removal of protecting allyl groups under exceedingly mild conditions. 

A series of pyrido[2,3-rf pyrimidine-2,4-diones bearing substituents at C-5 and/or C-6 were synthesized using palladium-catalyzed coupling of uracil derivative 417 with vinyl substrates or allyl ethers to give the regioisomeric mixtures of 418/419 and 420/421, respectively. The ratio of the isomeric structures was dependent on the substituent R. In the case of the reaction with -butyl vinyl ether, only the product 419 was obtained. However, the reactions with acrylonitrile, ethyl acrylate, 2-trifluoromethylstyrene, and 3-nitrostyrene afforded only 418. Also, reaction with allyl phenyl ether gave only 420. The key intermediate 417 was prepared by the reaction of 6-amino-l-methyluracil with DMF-DMA (DMA = dimethylacetamide), followed by N-benzylation with benzyl chloride and vinyl iodination with iV-iodosuccinimide (NIS) (Scheme 15) <2001BML611>. 

The isomerization of allyl ethers to 1-propenyl ethers, which is usually performed with potassium tert-butoxide in dimethyl sulfoxide, can also be carried out under milder conditions using tris(triphen-ylphosphine)rhodium chloride,208 and by an ene reaction with diethyl azodicarboxylate,209,210 which affords a vinyl ether adduct. Removal of an O-allyl group may be achieved by oxidation with selenium dioxide in acetic acid,211 and by treatment with N-bromosuccinimide, followed by an aqueous base.201,212... 

Allylic double bonds can be isomerized by some transition metal complexes. Isomerization of alkyl allyl ethers 480 to vinyl ethers 481 is catalysed by Pd on carbon [205] and the Wilkinson complex [206], and the vinyl ethers are hydrolysed to aldehydes. Isomerization of the allylic amines to enamines is catalysed by Rh complexes [207]. The asymmetric isomerization of A jV-diethylgeranylamine (483), catalysed by Rh-(5)-BINAP (XXXI) complex to produce the (f )-enaminc 484 with high optical purity, has been achieved with a 300 000 turnover of the Rh catalyst, and citronellal (485) with nearly 100% ee is obtained by the hydrolysis of the enamine 484 [208]. Now optically pure /-menthol (486) is commerically produced in five steps from myrcene (482) via citronellal (485) by Takasago International Corporation. This is the largest industrial process of asymmetric synthesis in the world [209]. The following stereochemical corelation between the stereochemistries of the chiral Rh catalysts, diethylgeranylamine (483), diethylnerylamine (487) and the (R)- and (5)-enamines 484... 

Propenyl Ethers and Unsaturated Cyclic Ethers Propenyl ethers (CH3—CH=CH—OR R = ethyl, isobutyl, etc. cis- and trans-isomers) and 3,4-dihydrofuran are linear and cyclic a,/3-unsaturated ethers, that can be regarded as / -substituted vinyl ether derivatives. For these monomers a few controlled/living cationic polymerizations have been reported. The HI/I2 system is generally effective for both linear and cyclic monomers [181,182,183], whereas a recent study by Nuyken indicates that the IBVE-HI adduct coupled with nBu4NC104 is suited for 3,4-dihydrofuran (see Section V.A.4) [184]. A variety of mono- and bifunctional propenyl ethers can readily be prepared by the ruthenium complex-catalyzed isomerization of corresponding allyl ethers [185]. 

Olefin isomerization catalyzed by ruthenium alkylidene complexes can be applied to the deprotection of allyl ethers, allyl amines, and synthesis of cyclic enol ethers by the sequential reaction of RCM and olefin isomerization. Treatment of 70 with allyl ether affords corresponding vinyl ether, which is subsequently converted into alcohol with an aqueous HCl solution (Eq. 12.37) [44]. In contrast, the allylic chain was substituted at the Cl position, and allyl ether 94 was converted to the corresponding homoallylic 95 (Eq. 12.38). The corresponding enamines were formed by the reaction of 70 with allylamines [44, 45]. Selective deprotection of the allylamines in the presence of allyl ethers by 69 has been observed (Eq. 12.39), which is comparable with the Jt-allyl palladium deallylation methodology. This selectivity was attributed to the ability of the lone pair of the nitrogen atom to conjugate with a new double bond of the enamine intermediate. 

As vinyl ethers were known to be poor substrates in Ru-catalyzed olefin metath-eses, it has been difficult to obtain cydic enol ethers by RCM of the vinyl ethers. Recently, a novel method to obtain cyclic enol ethers has been reported, which afforded cydic enol ethers directly from easily prepared dienes containing an allyl ether moiety [46]. Treatment of 70 with diene 99 in CH2CI2 in the presence of small amount of H2 resulted in a formation of dihydropyran 101 (Eq. 12.40). Treatment of 70 with H2 has been thought to produce an active catalyst for the olefin isomerization, and only metathesis products are formed until a small amount of H2 is introduced in the reaction. These results implied that this reaction most likely proceeded by way of a formation of the cyclic olefin 100, which was subsequently converted to dihydropyran 101 by the newly formed isomerization catalyst. In addition to the tandem reaction shown in Eq. 12.40, another method for obtaining cydic enol ethers from allyl ethers has also been demonstrated [46b]. This method induded addition of the hydride donor, such as NaBH4, to the reaction solution after the metathesis reaction had been completed. Although attempts to observe an active species for olefin isomerization in the presence H2 failed, these results suggested participation of hydride species in the olefin isomerization. 

As the photocatalytic carbon-carbon bond is formed, hydrogen evolves when the photocatalytic activation is done on colloidal ZnS [149, 150]. This dehydrodimerization also takes place with saturated ethers, with reactivity related to C H bond strength. Thus, 2,5-dihydrofuran (an allylic ether) is more easily activated than the isomeric 2,3-dihydrofuran (a vinyl ether). With the former substrate, all three dia-stereomeric coupling products are observed. Water is required for the reaction, and the primary photochemical product is thought to be a surface-bound hydroxyl radical. 

The reactions and product distributions thus far reported have been exclusively concerned with hexene. It was of interest to see whether the high specificity of positional substitution could be maintained with the other hexene isomers. By positional substitution specificity is meant ester attachment on ether of the carbons involved in the original carbon-carbon double bond. Table VII shows the results of these studies. The internal olefins reacted more slowly than the a-olefin, and with both palladium chloride-cupric chloride and 7r-hexenylpalladium chloride-cupric chloride systems high substitutional specificity (> 95% ) was also maintained with 2-hexene (Table VII). However, with 3-hexene the specificity is considerably lower (80%). Whether this is caused by 3-hexene isomerization prior to vinylation or by allylic ester isomerization is not known. A surprisingly high ratio of 2-substitution to 3-substitution is found ( 7 1) in the products from 2-hexene. An effect this large... 

One of the primary methods for the cleavage of allyl ethers is through isomerization of the olefin to the vinyl ether. The vinyl ether can then be cleaved by a number of methods. 

X. fran.v-Pd(NH3)2Cl2/f-BuOH isomerizes allyl ethers to vinyl ethers that can then be hydrolyzed in 90% yield, but in the presence of an a-hydroxy group the intermediate vinyl ether cyclizes to an acetal. This reagent does not affect benzylidene acetals. 

XV. Both the first and second generation Grubbs olefin metathesis catalysts have been shown to isomerize allylic ethers to vinyl ethers that are readily hydrolyzed.It is a decomposition product of the catalyst that was shown to be the isomerization catalyst. ... 

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