Ethyl Vinyl Ether Diels-Alder reactions

Cycloadditions with enol ethers The Diels-Alder reaction of vinyl ethers with a,(3-unsaturated aldehydes proceeds at room temperature when catalyzed by the related lanthanide Yb(fod),. An example is the reaction of crotonaldehyde with ethyl vinyl ether (equation I). 

The Knoevenagel products of sufficiently reactive acyclic as well as cyclic 1,3-dicarbonyls can act as oxadienes in hetero Diels-Alder reactions with enol ethers and enamines. Alkenes may be used as dieno-philes if the reaction is performed in an intramolecular mode. The cycloadditions of ethyl vinyl ether... 

To conclusively disprove the involvement of the chromanol methide radical, the reaction of a-tocopherol with dibenzoyl peroxide was conducted in the presence of a large excess of ethyl vinyl ether used as a solvent component. If 5a-a-tocopheryl benzoate (11) was formed homolytically according to Fig. 6.6, the presence of ethyl vinyl ether should have no large influence on the product distribution. However, if (11) was formed heterolytically according to Fig. 6.9, the intermediate o-QM 3 would be readily trapped by ethyl vinyl ether in a hetero-Diels-Alder process with inverse electron demand,27 thus drastically reducing the amount of 11 formed. Exactly the latter outcome was observed experimentally. In fact, using a 10-fold excess of ethyl vinyl ether relative to a-tocopherol and azobis(isobutyronitrile) (AIBN) as radical... 

The preparation of resin-bound nitroalkenes via a microwave-assisted Knoevenagel reaction of resin-bound nitroacetic acid with aryl and alkyl substituted aldehydes is reported. The potential of these resin-bound nitroalkenes for application in combinatorial chemistry is demonstrated by a Diels-Alder reaction with 2,3-dimethylbutadiene (Scheme 8.9). It is also used for one-pot three-component tandem [4+2]/[3+2] reactions with ethyl vinyl ether and styrene 46... 

The pyranocoumarin 105 can be prepared via a three-component Diels-Alder reaction between 4-hydroxycoumarin, ethyl vinyl ether and an a-dicarbonyl compound. Similarly to the above, upon treatment of 105 with sulfuric acid in THF, hydrolysis and rearrangement occur to give the furofurochromenone 106. The hemiacetal functionality in 106 may then be oxidized with pyridinium chlorochromate (PCC) to give the lactone 107 <2001EJ03711> (Scheme 28). 

Diels-Alder reaction, of acrolein with B-butyl cyclohexenyl ether, n-butyl vinyl ether, and ethyl isopropenyl ether, 34, 30... 

On the basis of available experimental data, it is impossible to choose a definite pathway of elimination of silanol. However, study of silylation of methyl P -nitropropionate (411) with BSA in the presence of trapping agents rigorously proved that silyl nitronate D is initially formed. This compound can be detected in the [3 + 2]-cycloaddition reaction with methyl acrylate product (413). If silylation of AN (411) is performed in the presence of ethyl vinyl ether, a-nitrosoalkene E can be successfully trapped in as heterodiene a Diels-Alder reaction. Dihydroox-azine (414) is formed, and its silylation affords isolable product (415). 

Waldmann et al. used tyrosinase which is obtained from Agaricus bisporus for the oxidation of phenols to give ortho-quinones via the corresponding catechols in the presence of oxygen (scheme 33).1881 A combination of this enzymatic-initiated domino process with a Diels-Alder reaction yields the functionalized bicyclic components 164 and 165 as a 33 1 mixture starting from simple p-methyl-phenol 160 in the presence of ethyl vinyl ether 163 as an electron rich dienophile via the intermediates 161 and 162 in an overall yield of 77%. 

Figure 26. Proposed stereochemical model for the hetero-Diels-Alder reaction of ethyl vinyl ether and acylphosphonate catalyzed by 55c-Cu(II) complex.

Recently, the first examples of catalytic enantioselective preparations of chiral a-substituted allylic boronates have appeared. Cyclic dihydropyranylboronate 76 (Fig. 6) is prepared in very high enantiomeric purity by an inverse electron-demand hetero-Diels-Alder reaction between 3-boronoacrolein pinacolate (87) and ethyl vinyl ether catalyzed by chiral Cr(lll) complex 88 (Eq. 64). The resulting boronate 76 adds stereoselectively to aldehydes to give 2-hydroxyalkyl dihydropyran products 90 in a one-pot process.The diastereoselectiv-ity of the addition is explained by invoking transition structure 89. Key to this process is the fact that the possible self-allylboration between 76 and 87 does not take place at room temperature. Several applications of this three-component reaction to the synthesis of complex natural products have been described (see section on Applications to the Synthesis of Natural Products ). 

Tetraacetylethene yields dihydropyrans in hDA reactions with ethyl vinyl ether and cyclopentadiene, but 1,2-dimethylenecyclohexane affords both the hDA and normal Diels-Alder adducts, the latter presumably arising via ring opening of the former adduct to a zwitterionic intermediate (Scheme 2) <99EJ03343>. 

Pyrrolo[2,3- ]pyridinones, 59, undergo an inverse electron demand Diels-Alder reaction with ethyl vinyl ether to generate 6-aza-5-carboline products in excellent yields but low stereoselectivity (Equation 4) <1997S73>. 

Photolysis of pyridoxine (vitamin B6) in aqueous solution at 254, 266, or 308 nm generates an o-quinone that may be trapped by ethyl vinyl ether in a Diels-Alder reaction <1998CC491>. 

The presence or absence of the dioxolane protecting group in dienes dictates whether they participate in normal or inverse-electron-demand Diels-Alder reactions.257 The intramolecular inverse-electron-demand Diels-Alder cycloaddition of 1,2,4-triazines tethered with imidazoles produce tetrahydro-l,5-naphthyridines following the loss of N2 and CH3CN.258 The inverse-electron-demand Diels-Alder reaction of 4,6-dinitrobenzofuroxan (137) with ethyl vinyl ether yields two diastereoisomeric dihydrooxazine /V-oxide adducts (138) and (139) together with a bis(dihydrooxazine A -oxide) product (140) in die presence of excess ethyl vinyl ether (Scheme 52).259 The inverse-electron-demand Diels-Alder reaction of 2,4,6-tris(ethoxycarbonyl)-l,3,5-triazine with 5-aminopyrazoles provides a one-step synthesis of pyrazolo[3,4-djpyrimidines.260 The intermolecular inverse-electron-demand Diels-Alder reactions of trialkyl l,2,4-triazine-4,5,6-tricarboxylates with protected 2-aminoimidazole produced li/-imidazo[4,5-c]pyridines and die rearranged 3//-pyrido[3,2-[Pg.460]

A complex reaction mixture (twelve 1 1 adduct isomers) was formed upon irradiation of ethyl vinyl ether and 4-cyanoanisole [87], Two major adducts, together comprising approximately 70%, were formed at <50% conversion. These 1 1 adducts reacted readily with. V-phenylmalcimidc (in refluxing toluene) and were isolated and separated as their Diels-Alder adducts. The structures of these 1 1 1 adducts could be assigned on the basis of their spectroscopic data, and from these structures, the primary ortho adducts could be identified as l-cyano-4-methoxy-8-ethoxy- and l-methoxy-4-cyano-7-ethoxybicyclo[4.2.0]octa-2.4-di-ene (Scheme 45). 

A DFT study of the polar Diels-Alder reaction of 4-aza-6-nitrobenzofuroxan with cyclopentadiene found only one highly asynchronous transition state structure associated with the formation of the 4 + 2-adduct.178 4-Nitrobenzodifuroxan has been shown to be a highly reactive nitroalkene in Diels-Alder reactions with common dienes (cyclopentadiene) to produce stable NED adducts and with ethyl vinyl ether to produce IED adducts.179 Unlike a-acylfuran, 2-nitrofurans have been shown to be active dienophiles in thermal NED Diels-Alder reactions with a variety of buta-1,3-dienes, including Danishefsky s diene.180... 

Predict the regioselectivity in the Diels-Alder reactions of acrolein and N-acetyl-2-cyano-4-phenyl-l-azabutadiene with 1-hexene, styrene, ethyl vinyl ether and methyl acrylate. The FOs of the azadiene are given below the others may be found in the Appendix. 

The reaction of hexachlorocyclopentadiene with electron-rich alkenes is classified as inverse electron demand Diels-Alder reaction, but its reaction with electron-poor alkenes is considered as a stepwise process based on a lack of stereospecificity. The cycloaddition of 7 with ethyl vinyl ether ... 

Wyler et al. [146a-c] have focused on the hetero Diels-Alder reaction of a,/)-unsaturated-acyl cyanides such as 2-140 with ethyl vinyl ether, N-methylated uracil and l-bromo-2-ethoxyethenes 2-141. In the latter case the dihydropyran... 

Desimoni and Righetti have been thoroughly investigating the effect of solvents, acid catalysis and salts on hetero Diels-Alder and ene reactions of 1-oxa-1,3-butadienes for a long time [ 154-156]. Recently, for the cycloaddition of 2-154 and ethyl vinyl ether 2-83 in the presence of lithium perchlorate in different solvents as diethyl ether, acetonitrile, acetone, methanol, iso-propanol to give... 

Tietze and Schuffenhauer explored the intermolecular hetero Diels-Alder reaction of ethyl vinyl ether and sulfinimine 204 and found that at high pressures (11 kbar) and long reaction times (48 h at room temperature), tetrahydropyridines 205 and 206 were obtained in 96% yield and in a ratio of 1.7 1.107 The exo-adducts were not observed. Phenyl vinyl sulfide reacts similarly, but simple alkenes failed. Theoretical calculations and the experimental results suggest that while the cycloaddition is concerted, it is highly asynchronous. 

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