Vinyl methyl ether adducts

Sheradsky has found that the hydroxyl function of a ketoxime such as acetophenone oxime can be made to react with DMAD when the reaction is carried out in methanol with a basic catalyst, to give mixture of the fumarate and maleate isomers (164) in the ratio 2 1. This mixture on heating undergoes a hetero-Cope rearrangement followed by cyclization and dehydration to give dimethyl 5-phenylpyrrole-2,3-dicarboxylate (168) (Scheme 25). Similarly, Heindel and Chun have reported that vinyl ether adducts (171), obtained by the condensation of arylamide oximes with DMAD, get thermally converted into oxa-diazolines (172) or imidazolinones (174), depending on the reaction conditions. A similar reaction occurs with aromatic amidoxime-methyl propiolate adducts to give imidazoles (170) (Scheme 26). 1,2,4-Dioxazoles have been reported to be formed in the reaction of hydrox-amic acids with DMAD. - ... 

Reipig (39,40), Pfaltz (41), and Andersson and their co-workers (42) independently showed that these catalysts are capable of effecting the selective cyclopropanation of enol ethers and enolsilanes. Methyl vinyl ketone and acetophenone enolsilanes provide high selectivities in the cyclopropane products, but both isomers are formed equally. The trisubstituted dihydropyran 65 leads to cyclopropane adducts in high diastereoselectivities and enantioselectivities using 55c CuOTf as catalyst. 

A study of the regioselectivity of the 1,3-dipolar cycloaddition of aliphatic nitrile oxides with cinnamic acid esters has been published. AMI MO studies on the gas-phase 1,3-dipolar cycloaddition of 1,2,4-triazepine and formonitrile oxide show that the mechanism leading to the most stable adduct is concerted. An ab initio study of the regiochemistry of 1,3-dipolar cycloadditions of diazomethane and formonitrile oxide with ethene, propene, and methyl vinyl ether has been presented. The 1,3-dipolar cycloaddition of mesitonitrile oxide with 4,7-phenanthroline yields both mono-and bis-adducts. Alkynyl(phenyl)iodonium triflates undergo 2 - - 3-cycloaddition with ethyl diazoacetate, Ai-f-butyl-a-phenyl nitrone and f-butyl nitrile oxide to produce substituted pyrroles, dihydroisoxazoles, and isoxazoles respectively." 2/3-Vinyl-franwoctahydro-l,3-benzoxazine (43) undergoes 1,3-dipolar cycloaddition with nitrile oxides with high diastereoselectivity (90% de) (Scheme IS)." " ... 

The metalation of vinyl ethers, the reaction of a-lithiated vinyl ethers obtained thereby with electrophiles and the subsequent hydrolysis represent a simple and efficient method for carbonyl umpolung. Thus, lithiated methyl vinyl ether 56 and ethyl vinyl ether 54, available by deprotonation with t- or n-butyllithium, readily react with aldehydes, ketones and alkyl halides. When the enol ether moiety of the adducts formed in this way is submitted to an acid hydrolysis, methyl ketones are obtained as shown in equations 72 and 73 . Thus, the lithiated ethers 56 and 54 function as an acetaldehyde d synthon 177. The reactivity of a-metalated vinyl ethers has been reviewed recently . 

Cycloadditions involving the more nucleophilic vinyl ethers are easier than those above and the reaction has considerable synthetic potential. The reactants are heated at 180-190 °C in a sealed vessel and the adduct is rapidly formed in high yield (50JA3079, 51JA5267). Full experimental details have been published for the synthesis of 3,4-dihydro-2-methoxy-4-methyl-2/f-pyran from methyl vinyl ether, and the same technique was used to prepare a further 13 dihydropyrans (630SC(4)3il>. 

Chiral crown ethers. Cram and Sogah4 have observed that potassium bases [KOC(CH3)3 or KNHj] complexed by the chiral crown ethers 1 or 2 catalyze asymmetric Michael additions to methyl vinyl ketone and to methyl acrylate to give adducts in 60 99% optical purity. 

Atkins et al. [130] reported in 1977 that irradiation of mixtures of benzene and methyl acrylate or methyl methacrylate, both acceptors, yields mixtures of endo and exo adducts. A subsequent report from the same groups [120] describes the results of the irradiations of benzene in the presence of ethyl vinyl ether, //-butyl vinyl ether, 2,3-dihydropyran, and 1,4-dioxene. In all these cases, the major products were exo-ortho photocycloadducts. The orientations of these vinyl ethers with respect to benzene, in their loose ground-state associations, were inferred from NMR spectra. For ethyl vinyl ether, n-butyl vinyl ether, 2,3-dihydropyran, and 1,4-dioxene, the vinyl proton resonances were either unaffected by a solvent change from carbon tetrachloride to hexadeuterobenzene or appeared 4-10 Flz downfield, whereas the methyl and/or methylene signals all moved up-field by 10-25 Hz. This implies an endo arrangement of the molecules in the ground state. Thus, the ortho photocycloadducts of vinyl ethers with benzene show exo stereochemistry, even when the ground-state orientation is endo. 

Use of the preformed Z-silyl enol ether 18 results in quite substantial anti/syn selectivity (19 20 up to 20 1), with enantiomeric purity of the anti adducts reaching 99%. The chiral PT-catalyst 12 (Schemes 4.6 and 4.7) proved just as efficient in the conjugate addition of the N-benzhydrylidene glycine tert-butyl ester (22, Scheme 4.8) to acrylonitrile, affording the Michael adduct 23 in 85% yield and 91% ee [10]. This primary product was converted in three steps to L-ornithine [10]. The O-allylated cinchonidine derivative 21 was used in the conjugate addition of 22 to methyl acrylate, ethyl vinyl ketone, and cydohexenone (Scheme 4.8) [12]. The Michael-adducts 24-26 were obtained with high enantiomeric excess and, for cydohexenone as acceptor, with a remarkable (25 1) ratio of diastereomers (26, Scheme 4.8). In the last examples solid (base)-liquid (reactants) phase-transfer was applied. 

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