Diels-Alder reaction, with vinyl ethers

Wada, E., Kanemasa, S., and Tsuge, O., New synthesis of 2-oxo-3-alkenylphosphonates and hetero Diels-Alder reactions with vinyl ethers leading to 5-substituted 2-phosphinyl-2-cyclohexen-l-ones, Bull. Chem. Soc. Jpn., 62, 860, 1989. 

Enamine-aldehydes (80) can also serve as the diene equivalent in the hetero-Diels-Alder reaction with vinyl ethers and yields of... 

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... 

Azadienes undergo Diels-Alder reactions to form pyridine, dihydro- and tetrahydropyridine derivatives. N-Vinyl lactim ethers undergo Diels-Alder reactions with a limited set of dienophiles. " Thioketones react with dienes to give Diels-Alder cycloadducts. The carbonyl group of lactams have also been shown to be a dienophile. Certain heterocyclic aromatic rings (among them furans) can also behave as dienes in the Diels-Alder reaction. Some hetero dienes that give the reaction are -C=C-C=0, 0=C-C=0, and N=C-C=N. ... 

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 reactivity of the produced complexes was also examined [30a,b]. Since the benzopyranylidene complex 106 has an electron-deficient diene moiety due to the strong electron-withdrawing nature of W(CO)5 group, 106 is expected to undergo inverse electron-demand Diels-Alder reaction with electron-rich alkenes. In fact, naphthalenes 116 variously substituted at the 1-, 2-, and 3-positions were prepared by the reaction of benzopyranylidene complexes 106 and typical electron-rich alkenes such as vinyl ethers, ketene acetals, and enamines through the Diels-Alder adducts 115, which simultaneously eliminated W(CO)6 and an alcohol or an amine at rt (Scheme 5.35). 

The benzoxazoles 59 and 60 can act as azadienes in Diels-Alder reactions with nucleophilic alkenes such as vinyl ethers <98JCS(P1)3389>. ... 

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>. 

Httero-Diels-Alder reactionAcrolein undergoes a Diels-Alder reaction with furanoid and pyranoid exocyclic vinyl ethers at 25 (4 6 days). The spirokelal (2) obtained can be oxidized in CHiOH by w-chloroperbenzoic acid to the ring... 

Diels-Alder reactions with p-quinones (6. 65 66). The orientation of Diels-Alder reactions of 6-meihoxy-l-vinyl-3,4-dihydronaphthalene (1) with p-quinones is subject to reversal by addition of BF, etherate (1.3 equivalent). Thus the thermal reaction with 2,6-dimethyl-/>-bcnzoquinone (2) results in exclusive formation of 3, whereas the catalyzed reaction leads predominately to the isomer 4. The adduct 3 is stable to base, but the syn, m-isomer 4 on treatment with NaX O, is converted to the more stable anti, frau.s-isomer 5. 

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... 

Oxidation of the o/T/zo-substituted acetanilides 324 with DMP leads to the isolable o-iminobenzoquinones 325 (Scheme 94) (02JA2221). The imino-quinones undergo inverse electron demand Diels-Alder reactions with the vinyl ether and vinyl sulfide shown in Scheme 94, thus providing access to the benzoxazine derivatives 326 and 327. 

Much larger effects of this type are observed in cycloadditions of enol ethers to tetrazines (Fig. 26), a reaction shown by Sauer and co-workers to be an example of a Diels-Alder reaction with inverse electron demand 75. The rates of 3,6-di-(2 -pyridyl)-s-tetrazine to various enol ethers and styrenes are summarized in Fig. 27. These were obtained by measuring the disappearance of the 540 nm band in the absorption spectra of the tetrazine76. These results are of particular interest, since there is little or no correspondence between the electron-donor ability of the enol ether, as measured by the ir ionization potentials (Table 5), and the rate of reaction of the enol ether. For example, although the conversion of methyl vinyl ether to 1,1-dimethoxyethylene results in a 4.3 times increase in rate, in line with the 0.2 — 0.3 eV decrease in IP, the 1,2-dimethoxyethylenes are 13 to 25 times less reactive than methyl vinyl ether, even though the IPs of these molecules are much lower... 

A total synthesis of adaline (550) has been performed (73BSB699). The vinyl ketone 547 was submitted to hetero Diels-Alder reaction with methyl vinyl ether to yield the dihydropyran derivative 548 in 60% yield. Acid hydrolysis of 548 produced the keto aldehyde 549. Finally, a Mannich reaction involving... 

Formation of a cation radical of the diene may catalyze Diels-Alder reactions with certain dienophiles thus oxidation of substituted vinylindoles to the cation radical in the presence of a push-pull dienophile may form different heterocyclic compounds by the Diels-Alder reaction, for instance pyrido[l,2i7]indoles from vinylindoles and yS-enamino-esters [33]. Similarly, anodic oxidation in MeCN of certain oxazolidines in presence of vinyl ether leads to derivatives of oxazepines in a catalytic reaction in which the ring-opened radical cation of the oxazolidine adds to the vinyl ether and the radical cation of the resulting oxazepine oxidizes the oxazolidine [34]. 

Generally, on PhI(OAc)2-promoted oxidation of o-methoxyphenols in MeOH containing a large excess of electron-rich dienophiles, the resulting o-quinone monoketals may undergo an intermolecular Diels-Alder reaction with the dienophiles to afford the corresponding dimers. 4-Methoxycarbonyl-2-methoxyphenol (421) was submitted to PhI(OAc)2-promoted oxidation in MeOH containing benzyl vinyl ether (BVE) or dihydrofuran (DHF)... 

Diethyl 2-oxo-3-alkenylphosphonates, which are readily accessible from diethyl 2-oxopropylphos-phonate, are useful heterodienes in Diels-Alder reactions. Cycloaddition reactions with vinyl ethers in ( I I in a sealed tube at 85-130°C give satisfactory yields (57-88%) of dihydro-27/-pyrans. The products are isolated as a mixture of 2,4-tra .v and 2,4-czT isomers. When treated with 4 M HCl in THF, the dehydropyran hemiacetal moiety is readily hydrolyzed to provide diethyl 5-formyl-2-oxopentylphosphonates in excellent yields (72-92%, Scheme 5.59). When R> = R =H, the aldehyde undergoes smooth cyclization leading to diethyl 2-oxocyclohexenephosphonate. ... 

The reactivity of 4,6-benzo[/ ][l,7]naphthyridine in Diels-Alder reactions with maleic acid and dimethyl acetylenedicarboxylate was examined. The reaction afforded adduct 332 (1996MI5). 6-Ethoxycarbonyl- 333a and phenacylmethylides 333b were used as 1,3-dipolar reagents in reactions with methacrylic acid, methyl methacrylate, butyl vinyl ether, methyl vinyl ketone, maleic anhydride and dimethyl acetylenedicarboxylate (1996MI5, 1999AJC149). 

The hetero-Diels-Alder reaction with inverse electron demand is an attractive route for the synthesis of 3.4-dihydro-2//-pyrans. Enone 7, esterified with D-mandelic acid as chiral auxiliary, adds to ethyl vinyl ether (8) to give a 2 1 mixture of 9 and 10 [d.r. (2S,4S) (2RAR) 67 33]1. The enone 11 requires high pressure to add to the much less reactive enol ether 12, yielding a 2 3 mixture of 13 and 14 [d.r. (2S, 3S,45 )/(21 ,37 ,4/ ) 40 60]8. The introduction of the additional stereogenic center in the enone 15 leads to a substantially improved diastereofacial selectivity, and adducts 16 and 17 are obtained as a 1 10 mixture [d.r. (2S.4S) (2RAR) 9 91]9. 

The thermal and photochemical [4 + 2] cycloadditions of o-quinones with olefinic and acetylenic dienophiles have been extensively reviewed4,5,200 and include their 4tt heterodiene Diels-Alder reactions with olefins,201-204 vinyl ethers,205 enamines,206 selected dienes,207-209 dipheny-lketenimines,210 ketenes,209,210 fulvenes,211 and selected heterocycles including furan,207-209,212 benzofuran,209,212,215 indoles,213 azepines,214 and 1,2-diazepines.214 The tetrahalo-substituted o-quinones, tetrachloro- and tetrabromo-o-quinone, generally participate in heterodiene [4 + 2] cycloadditions at an increased rate over the unsubstituted systems and generally provide higher overall yields of the Diels-Alder products.4,5 With simple olefins, the dienophile geometry is maintained in the course of the thermal [4 4- 2] cycloadditions [Eq. (52)],203,204... 

AAAcylimines, e.g., 4, are the most widely recognized and the most extensively investigated hetero-2-azadiene system capable of participation in Diels-Alder reactions, and comprehensive reviews have been published.7,71 In general, substituents X and Y are strongly electron-withdrawing groups and consequently the AAacylimines participate as electron-deficient partners in cycloaddition reactions with electron-rich dienophiles. Diels-Alder reactions of electron-deficient /V-acylimines with vinyl ethers, enamines, olefins, sulfenes, acetylenes, and the carbon-carbon or carbon-oxygen double bond of ketenes have been detailed.57 71 This 47t participation of electron-deficient AAacylimines does complement the ability of many simple AAacylimines to behave as 2ir dienophile components in Diels-Alder reactions with typical electron-rich dienes.6... 

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