Acylation of vinyl ethers

Vinyl ethers yield acylated vinyl ethers when they are reacted with aroyl chlorides or 3-thienylcarbo-nyl chloride, triethylamine and a palladium acetate catalyst at 60-70 C (equation 43).103 The products of this reaction are useful 1,3-dicaibonyl equivalents. At higher temperatures the reaction yields arylated vinyl ethers. It is interesting that the acylations of vinyl ethers are regioselective while the direct aryla-tions are usually not.104... 

Hojo, M., R. Masuda, G. Kokuryo et al. 1976. Electrophilic substitutions of olefinic hydrogens. II. Acylation of vinyl ethers and N-vinyl amides. Chem. Lett 5 499-502. 

Acylation of enol ethers. Reaction of 1 with ethyl vinyl ether in ether provides an intermediate that undergoes dehydrochlorination when heated to provide the trichloromethyl ketone 2, which is converted by base (haloform reaction) to the ester 3 in high yield. 

Acylation in the 6-position of 4-arylaminoquinazolines 93 has been performed via the intermediacy of vinyl ethers 94 which were introduced by a Stille reaction using vinylstannanes <2003BML637>. 

Enol Ethers and Esters 0-15 O-Alkylation of carbonyl compounds with diazo alkanes 0-17 Transetherification 0-20 Reaction between acyl halides and active hydrogen compounds 0-23 Transesterification 0-24 Acylation of vinylic halides 0-94 Alkylation with ortho esters 0-107 O-Acylation of 1,3-dicarbonyl compounds... 

Phosphine oxide anions are often superior to ylids in olefmation reactions, and the anion of 68, made with lithium di-isopropyl-amide (LDA), has none of the disadvantages of the ylid 67. We have made 41 a range of vinyl ethers 70 this wayc, and as part of a synthesis of stiychnos alkaloids43, we were able41 to convert the acyl indole 71 into the aldehyde 72... 

Originally the monomer in Fig. 9 was prepared by DuPont by the synthetic scheme shown in Fig. 12 [33]. Thermolysis of the acyl fluoride in Fig. 12 did not give a desired monomer but gave a cyclo compound. In order to prevent the cyclization, a new synthetic route was developed as shown in Fig. 13, which was applied to the synthesis of Dow membranes [34]. A chlorine atom was introduced to the acyl fluoride to improve the selectivity of vinyl ether formation. The Dow membrane was also developed for brine electrolysis, but was not commercialized probably because of its high cost. Difficulty in the preparation of the acyl fluoride in Fig. 13 is one of the causes. Recently, new synthetic processes for the short side chain monomer were developed, as represented in Fig. 14. 

Recent advances in methods of preparation of organometallic derivatives of vinyl ethers have provided another group of acyl anion equivalents. 

In contrast to the hydrolysis of prochiral esters performed in aqueous solutions, the enzymatic acylation of prochiral diols is usually carried out in an inert organic solvent such as hexane, ether, toluene, or ethyl acetate. In order to increase the reaction rate and the degree of conversion, activated esters such as vinyl carboxylates are often used as acylating agents. The vinyl alcohol formed as a result of transesterification tautomerizes to acetaldehyde, making the reaction practically irreversible. The presence of a bulky substituent in the 2-position helps the enzyme to discriminate between enantiotopic faces as a result the enzymatic acylation of prochiral 2-benzoxy-l,3-propanediol (34) proceeds with excellent selectivity (ee > 96%) (49). In the case of the 2-methyl substituted diol (33) the selectivity is only moderate (50). 

The chiral BOX-copper(ll) complexes, (S)-21a and (l )-21b (X=OTf, SbFg), were found by Evans et al. to catalyze the enantioselective cycloaddition reactions of the a,/ -unsaturated acyl phosphonates 49 with ethyl vinyl ether 46a and the cyclic enol ethers 50 giving the cycloaddition products 51 and 52, respectively, in very high yields and ee as outlined in Scheme 4.33 [38b]. It is notable that the acyclic and cyclic enol ethers react highly stereoselectively and that the same enantiomer is formed using (S)-21a and (J )-21b as the catalyst. It is, furthermore, of practical importance that the cycloaddition reaction can proceed in the presence of only 0.2 mol% (J )-21a (X=SbF6) with minimal reduction in the yield of the cycloaddition product and no loss of enantioselectivity (93% ee). 

More recently, further developments have shown that the reaction outlined in Scheme 4.33 can also proceed for other alkenes, such as silyl-enol ethers of acetophenone [48 b], which gives the endo diastereomer in up to 99% ee. It was also shown that / -ethyl-/ -methyl-substituted acyl phosphonate also can undergo a dia-stereo- and enantioselective cycloaddition reaction with ethyl vinyl ether catalyzed by the chiral Ph-BOX-copper(ll) catalyst. The preparative use of the cycloaddition reaction was demonstrated by performing reactions on the gram scale and showing that no special measures are required for the reaction and that the dihydro-pyrans can be obtained in high yield and with very high diastereo- and enantioselective excess. 

Sulfur-stabilized ylides underwent photodriven reaction with chromium alkoxy-carbenes to produce 2-acyl vinyl ethers as E/Z mixtures with the E isomer predominating (Table 22) [ 121-123]. The reaction is thought to proceed by nucleophilic attack of the ylide carbon at the chromium carbene carbon followed by elimination of (CO)5CrSMe2. The same reaction occurred thermally, but at a reduced rate. Sulfilimines underwent a similar addition/elimination process to produce imidates or their hydrolysis products (Table 23) [ 124,125]. Again the reaction also proceeded thermally but much more slowly. Less basic sulfilimines having acyl or sulfonyl groups on nitrogen failed to react. 

Recently Lin and coworkers have developed a selective synthesis of N-acyl and 0-acyl propanolol vinyl derivatives by enzyme-catalyzed acylation of propanolol using divinyl dicarboxylates with different carbon chain lengths (Scheme 7.10) [24]. Lipase AY30 in diisopropyl ether demonstrated high chemoselectivity toward the amino... 

We investigated lipase-catalyzed acylation of 1-phenylethanol in the presence of various additives, in particular an E. additive using diisopropyl ether as solvent. Enhanced enantioselectivity was obtained when a BEG-hased novel IE, i.e., imidazolium polyoxyethylene(lO) cetyl sulfate, was added at 3-10 mol% vs. substrate in the Burkholderia cepacia lipase (hpase PS-C) catalyzed transesterification using vinyl acetate in diisopropyl ether or a hexane solvent system. ... 

The resulting complexes can be effectively employed as single component catalysts to homopolymerize ethylene or copolymerize ethylene with acrylates [50, 51] and a variety of other polar monomers including vinyl ethers, [51,52] vinyl fluoride [53], iV-vinyl-2-pyrrolidinone, and AMsopropylacrylamide [54], In fact, the resulting catalysts are so robust that they can be used as single component catalysts in aqueous emulsion homo-polymerization of ethylene and copolymerization of ethylene with norbomenes and acylates [55]. 

The reactions of nitroalkenes (42) with various enols (43b) (vinyl ethers, silyl, and acyl enolates, ketene acetals) have been studied in most detail (110, 111, 125—154). As a mle, these reactions proceed smoothly to give the corresponding nitronates (35f) in yields from high to moderate. As in the reactions with enamines, the formation of compounds (44b) is attributed to the ambident character of the anionic centers in zwitterionic intermediates analogous to those shown in Scheme 3.43. 

The detailed mechanism of inhibition of TEM-2 (class A) enzyme with clavulanate has been established (Scheme 1) [23,24], The inhibition is a consequence of the instability of the acyl enzyme formed between the /1-lactam of clavulanate and the active site Ser-70 of the enzyme. In competition with deacylation, the clavulanate acyl-enzyme complex A undergoes an intramolecular fragmentation. This fragmentation initially provides the new acyl enzyme species B, which is at once capable of further reaction, including tautomeriza-tion to an entity C that is much less chemically reactive to deacylation. This species C then undergoes decarboxylation to give another key intermediate enamine D, which is in equilibrium with imine E. The imine E either forms stable cross-linked vinyl ether F, by interacting with Ser-130 or is converted to the hydrated aldehyde G to complete the inactivation. 

Being aware of the fact that a hetero-substituted carbon-carbon double bond is convertible into a carbonyl group, one can use a-hetero-substituted lithio-alkenes 2 as nucleophilic acylation reagents 142 and 143, which display the umpoled d reactivity, provided that the carbanionic character is effective. Depending on the hetero-snbstitnent X, the conversion of the vinyl moiety into a carbonyl gronp can be effected either by hydrolysis or by ozonolysis. The former procednre has been applied preferentially in the case of lithiated vinyl ethers, whereas the latter has been nsed in particnlar for cleavage of the double bond in such products that result from the reaction of hthiated vinyl bromides with electrophiles (Scheme 17). 

Enehydroxylamines (102) are invoked as intermediates in the rearrangement of O-vinyl, acyl or aryl oximes (101) (equation 31). Varlamov and coworkers demonstrated that the heterocyclization of ketoximes (103) with acetylene in snper basic medium and in the presence of metal hydroxides proceeds by a [3,3]-sigmatropic rearrangement of the enehydroxylamine 105 of the corresponding oxime vinyl ethers 104 (equation 32). The unreactivity of 3-methyl-2-azabicyclo[3.3.1]nonan-9-one oxime (106) in the same reaction conditions was explained by its inability to isomerize to the corresponding enehydroxylamine. 

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