Ethylenic acetals substitution reactions

To synthesize isomeric 3-substituted isoxazoles (301) the reaction of ethylene acetals of )3-ketoaldehydes (300) (readily available from -chlorovinyl ketones (57IZV949)) with hydroxylamine was employed. Owing to the comparative stability of the dioxolane group, this reaction gave exclusively 3-substituted isoxazoles (301) (60ZOB954). The use of noncy-clic, alkyl S-ketoacetals in this reaction resulted in a mixture of 3- and 5-substituted isoxazoles (55AG395). 

The coupling reaction of the cyelopropylcuprates 87 with the 4-chloro-cyclobutenones 75 or their ethylene acetals 86 is useful for preparing the 4-cyclopropyl-2-cyclobutenones 88. The ring fission of 88 to the cyclohep-tadienones 89 is performed by a Rh(I)-catalyst. The less substituted cyclopropane ring bond is cleaved selectively. Cyclooctadienones are obtained by using 4-cyclobutyl-2-cyclobutenones [43]. (Scheme 31)... 

Reaction between C2 symmetric diols and a, yS-unsaturated aldehydes yield chiral ethylenic acetals that undergo copper-mediated substitution reactions. With aryl or... 

Suzuki T, Oriyama T (1999) Novel reactions of ethylene acetals with silyl-substituted nucleophiles. A mild and efficient procedure for the synthesis of homoallyl alkyl ethers and unsymmetrical dialkyl ethers. Synth Commun 29 1263-1269... 

It was found that 3-phenylthiopropanal ethylene acetal (50) is a useful starting material for the preparation of 3-acylfurans (79CL709). Several 3-acylfurans have been discovered in nature (B-59MI31200) but few syntheses have been reported (77JOC1089) except those starting from a 3-substituted furan. Some 3-acylfurans, including perilla ketone, 3-(4-methylpentanoyl)furan, have now been prepared from the acetal (50) and an N-acylaziridine, or an aldehyde and subsequent oxidation. Deacylation reactions are suppressed by the use of 3-phenylthiopropanal ethylene acetal (50), and it affords the desired... 

Dowex SOW has also been used as an acid catalyst in the formation of substituted acetals (eq 23). Nishiguchi has shown that the optimum amount of Dowex SOW needed for an efficient synthesis of monoacetal (26) was 0.1 g per mmol of ethylene glycol. This reaction Is particularly impressive since it minimized the competitive formation of the diacetal (27). 

Cu-catalysed substitution of allyl ethers (alkoxide leaving group). Very similar synthetically useful reactions are exhibited by a-ethylenic acetals and ortho-esters. ... 

Nucleophilic substitutions reactions with organocopper compounds or the more widely applied organocyanocuprates in the presence of Lewis acids have been reported on a./S-ethylenic acetals and allylic mesylates or acetates. Mangeney and co-workers have reported regio- and diastereoselective Sn2 or Sn2 reactions on chiral acetals of cyclic aldehydes promoted by PhCu and Furthermore, organocoppers react efficiently... 

Reactions of the 2-amino-4,5-substituted thiazole (52) in acetic acid with ethylene oxide has been reported to give the N-exocyclic disubstitution product (S3) (201) in a 40% yield (Scheme 38). The reactive species in this reaction is probably the carbocation generated in acetic acid by ethvlene oxide. 

A large number of pyridazines are synthetically available from [44-2] cycloaddition reactions. In one general method, azo or diazo compounds are used as dienophiles, and a second approach is based on the reaction between 1,2,4,5-tetrazines and various unsaturated compounds. The most useful azo dienophile is a dialkyl azodicarboxylate which reacts with appropriate dienes to give reduced pyridazines and cinnolines (Scheme 89). With highly substituted dienes the normal cycloaddition reaction is prevented, and, if the ethylenic group in styrenes is substituted with aryl groups, indoles are formed preferentially. The cycloadduct with 2,3-pentadienal acetal is a tetrahydropyridazine derivative which has been used for the preparation of 2,5-diamino-2,5-dideoxyribose (80LA1307). 

The direct combination of selenium and acetylene provides the most convenient source of selenophene (76JHC1319). Lesser amounts of many other compounds are formed concurrently and include 2- and 3-alkylselenophenes, benzo[6]selenophene and isomeric selenoloselenophenes (76CS(10)159). The commercial availability of thiophene makes comparable reactions of little interest for the obtention of the parent heterocycle in the laboratory. However, the reaction of substituted acetylenes with morpholinyl disulfide is of some synthetic value. The process, which appears to entail the initial formation of thionitroxyl radicals, converts phenylacetylene into a 3 1 mixture of 2,4- and 2,5-diphenylthiophene, methyl propiolate into dimethyl thiophene-2,5-dicarboxylate, and ethyl phenylpropiolate into diethyl 3,4-diphenylthiophene-2,5-dicarboxylate (Scheme 83a) (77TL3413). Dimethyl thiophene-2,4-dicarboxylate is obtained from methyl propiolate by treatment with dimethyl sulfoxide and thionyl chloride (Scheme 83b) (66CB1558). The rhodium carbonyl catalyzed carbonylation of alkynes in alcohols provides 5-alkoxy-2(5//)-furanones (Scheme 83c) (81CL993). The inclusion of ethylene provides 5-ethyl-2(5//)-furanones instead (82NKK242). The nickel acetate catalyzed addition of r-butyl isocyanide to alkynes provides access to 2-aminopyrroles (Scheme 83d) (70S593). 

Due to its commercial importance, the synthesis of copper phthalocyanine (PcCu) is the best investigated of all the phthalocyanines. Copper phthalocyanine is prepared from phthalonitrile and copper(I) chloride without solvent137 and also in a melt of urea.229,277 Additionally, the insertion of copper into metal-free phthalocyanine in butan-l-ol and pentan-l-ol is possible. The copper salts used in this case are copper(I) chloride112 and copper(II) acetate.290 Starting from copper(II) acetate, copper phthalocyanine can also be prepared in ethylene glycol.127 As mentioned above, copper phthalocyanine often occurs as a byproduct of the Rosenmund-von Braun reaction. To increase the yield of the phthalocyanine the solvent dimethylformamide can be substituted by quinoline. Due to the higher boiling point of quinoline, the copper phthalocyanine is the main product of the reaction of copper(I) cyanide and 1,2-dibromoben-zene.130... 

As previously discussed, solvents that dissolve cellulose by derivatization may be employed for further functionahzation, e.g., esterification. Thus, cellulose has been dissolved in paraformaldehyde/DMSO and esterified, e.g., by acetic, butyric, and phthalic anhydride, as well as by unsaturated methacrylic and maleic anhydride, in the presence of pyridine, or an acetate catalyst. DS values from 0.2 to 2.0 were obtained, being higher, 2.5 for cellulose acetate. H and NMR spectroscopy have indicated that the hydroxyl group of the methy-lol chains are preferably esterified with the anhydrides. Treatment of celliflose with this solvent system, at 90 °C, with methylene diacetate or ethylene diacetate, in the presence of potassium acetate, led to cellulose acetate with a DS of 1.5. Interestingly, the reaction with acetyl chloride or activated acid is less convenient DMAc or DMF can be substituted for DMSO [215-219]. In another set of experiments, polymer with high o -celliflose content was esterified with trimethylacetic anhydride, 1,2,4-benzenetricarboylic anhydride, trimellitic anhydride, phthalic anhydride, and a pyridine catalyst. The esters were isolated after 8h of reaction at 80-100°C, or Ih at room temperature (trimellitic anhydride). These are versatile compounds with interesting elastomeric and thermoplastic properties, and can be cast as films and membranes [220]. 

Nitroimidazoles substituted by an aromatic ring at the 2-position are also active as antitrichomonal agents. Reaction of p-fluorobenzonitrile (83) with saturated ethanolic hydrogen chloride affords imino-ether 84. Condensation of that intermediate with the dimethyl acetal from 2-aminoacetaldehyde gives the imidazole 85. Nitration of that heterocycle with nitric acid in acetic anhydride gives 86. Alkylation with ethylene chlorohydrin, presumably under neutral conditions, completes the synthesis of the anti-... 

Although aryl halides are the substrates of choice for Heck transformations, dia-zonium salts have also gained great interest, due mainly to reasons of economy [478]. With this in mind, the group of Beller explored a domino diazotization/Heck sequence of substituted anilines 2-935 with ethylene (Scheme 2.209) [479]. The reaction proceeds best in the presence of Pd(OAc)2 and tBuONO as diazotization reagent in a mixture of acetic acid and CH2C12. Using these conditions, the desired styrenes 2-936 were isolated in yields up to 72 %. 

This regioselectivity is practically not influenced by the nature of subsituent R. 3,5-Disubstituted isoxazolines are the sole or main products in [3 + 2] cycloaddition reactions of nitrile oxides with various monosubstituted ethylenes such as allylbenzene (99), methyl acrylate (105), acrylonitrile (105, 168), vinyl acetate (168) and diethyl vinylphosphonate (169). This is also the case for phenyl vinyl selenide (170), though subsequent oxidation—elimination leads to 3-substituted isoxazoles in a one-pot, two-step transformation. 1,1-Disubstituted ethylenes such as 2-methylene-1 -phenyl-1,3-butanedione, 2-methylene-1,3-diphenyl- 1,3-propa-nedione, 2-methylene-3-oxo-3-phenylpropanoates (171), 2-methylene-1,3-dichlo-ropropane, 2-methylenepropane-l,3-diol (172) and l,l-bis(diethoxyphosphoryl) ethylene (173) give the corresponding 3-R-5,5-disubstituted 4,5-dihydrooxazoles. 

---