Diels-Alder reactions with vinyl ketones

The ability of 1,2 (or l,6)-dihydropyridines to undergo a Diels-Alder reaction with dienophiles such as methyl vinyl ketone, methyl acrylate, and acrylonitrile has been utilized in the synthesis of polyfunctional isoquinuclidine as a key intermediate in the synthesis of aspidosperma- and iboga-type alkaloids (66JA3099). 

Intermolecular befera-Diels-Alder reactions of enamino ketones with highly substituted vinyl ethers. Effect of high pressure on the kinetics and diastereoselectivity [77]... 

Linders, J.T.M., Briel, P., Fog, E., Lie, T.S. and Maat, L., Chemistry of opium alkaloids, Part XXVIII preparation of 6-demethoxy-N-formyl-N-northebaine and its Diels-Alder reactions with methyl vinyl ketone and nitroethene novel 8-nitro-substituted 6a,14a-ethenoisomorphinans and 6 3,14 3-ethenomorphinans, Rec. 

In order to introduce functionality at key positions, an intramolecular Diels-Alder reaction with furan as the diene component was planned. Suzuki coupling of the previously mentioned 105 with furan-3-boronic acid 106 gave compound 107, which was N-tosylated to 108. Construction of the dienophile portion was performed as in the previous case, by addition of vinylmagne-sium bromide to give 109, followed by MnC>2 oxidation to give the cyclization precursor, which was immediately heated at 120 °C in toluene and afforded compound 110, which incorporates an oxygen atom at both the ketone and vinyl chloride positions of welwistatin (Scheme 24). 

Diels-Alder reactions of the type shown in Table 15.1, that is, Diels-Alder reactions between electron-poor dienophiles and electron-rich dienes, are referred to as Diels-Alder reactions with normal electron demand. The overwhelming majority of known Diels-Alder reactions exhibit such a normal electron demand. Typical dienophiles include acrolein, methyl vinyl ketone, acrylic acid esters, acrylonitrile, fumaric acid esters (irans-butenedioic... 

Diels-Alder reactions carbohydrates.2 This 3,y-unsaturated a-keto ester undergoes Diels-Alder reactions with electron-rich dienophiles to provide protected sugars. The thermal and pressure-promoted reaction of 1 with ethyl vinyl ketone provides the endo-adduct 2, which can be converted in two steps into the ethyl (3-mannopyranoside 3. The same reaction of 1 with (Z)-l-acetoxy-2-benzy-loxyethylene is even more endo-selective, and gives the endo-adduct 4, which can be converted into a derivative of benzyl DL-mannopyranoside. 

Diene (53) undergoes Diels-Alder reactions with unsymmetrical dienophiles such as methyl vinyl ketone to give preferentially the adduct (55). Further manipulations of (55), such as acid hydrolysis to an a-phe-nylthiocycldiexanone (56), were carried out. 

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... 

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 synthesis starts from thebeine, which is subjected to a Diels-Alder reaction with methyl vinyl ketone and then reacted with n-butylmagnesium chloride. Finally, in a nucleophilic substitution, the methoxy-group is replaced by hydroxy. 

Methylenecyclobutanes are readily obtained by the condensation of an olefin with an allene. Thus, reaction of (221) with acrylonitrile gives (222) and the cyclohexenes (223), the latter resulting from prior rearrangement of (221) to 2-chlorobuta-1,3-diene followed by Diels-Alder reaction with acrylonitrile. Compound (222) cyclizes on dehydrochlorination to the unstable 3-methylenebicyclo[2,l,0]pentane (224). A second route to a 3-cyanomethylenecyclobutane involves vinyl Grignard addition to the ketones (225) and chlorination of the resulting alcohol (226 X = OH), which affords a mixture of (226 X = Cl) and (227). ... 

Tietze reported a domino-Knoevenagel-hetero-Diels-Alder reaction involving a three-component reaction between an a-nitroketone, formaldehyde, and an alkyl vinyl ether. In one example, a Knoevenagel condensation between ketone 105 and formaldehyde (106) yields electron-poor hetero-diene 108 that undergoes an inverse electron demand Diels-Alder reaction with ethyl vinyl ether to furnish dihydropyran 109. Tietze subsequently converted 109 into the deoxysugar (+)-forosamin. ... 

Chemoselective Diels-Alder Reaction with a,fi-Unsaturated Aldehydes and Ketones. Br0nsted acid (1) is an effective catalyst for the chemoselective Diels-Alder reaction of cyclopentadiene with acrolein and ethyl vinyl ketone (eq 3). The reaction catalyzed by (1) proceeds smoothly and shows high chemoselectivity for ethyl vinyl ketone, although the catalytic activities of methanesulfonic acid and p-toluenesufibnic acid are poor. However, some Lewis acids such as SnCLj and B(C6Fs)3 show high chemoselectivity for acrolein. 

Ultrasound has been exploited in the zinc mediated generation of a number of reactive intermediates. Most of these are only normally attainable in very low yield as a result of the forcing conditions necessary for their generation. On the other hand Han and Boudjouk showed that ortho-xylylene (35) was readily available from o-dibromoxylene. Trapping the intermediate tetraene with methyl vinyl ketone gave an 87 % yield of the product (36) arising from Diels-Alder reaction with the exocyclic diene [154] (Scheme 72). 

Trimethylsilylmethyl-1,3-butadiene undergoes highly re-gioselective aluminum chloride-catalyzed Diels-Alder reactions with dienophiles such as acrolein and methyl vinyl ketone in which the "para isomers are obtained almost exclusively (eqs 13 and 14). The adducts are converted readily to a variety of naturally occurring mono- and sesquiterpenes (eq 15). ... 

A detailed study of the cycloaddition of trifluoromethylethene has appeared as has work on a-siloxy-a -unsaturated ketones as dienophiles under Lewis-acid catalysis. Amongst the new dienophiles that have been reported are the two novel ketene equivalents methyl methoxypropiolate (129) and methyl phenyl-thiopropiolate (130). A series of 3-(acyloxy)but-3-en-2-ones (131) has been prepared and used as dienophiles in a route to anthracylinones, and, as part of a route to highly functionalized cyclohexenones, the vinyl sulphone (132) has been used in a Diels-Alder reaction with various dienes. ... 

Diels-Alder reactions with unsymmetrical dienes and/or dienophiles can lead to the formation of different isomers. One of the most interesting aspects in these systems is stereoselectivity, as observed in reactions involving cyclic dienes. In these cases, two different stereoisomers can be formed endo and exo (Scheme 2). Experimental observations show that in most cases the endo product is predominant over the exo one. Theoretical calculations do not always agree with the experimentally observed endo exo selectivity. Jorgensen et al. have shown that the computed endo/exo selectivity is dependent on the level of calculation for the reactions of acrylonitrile (5) and methyl vinyl ketone (6) with cyclopentadiene. 

Table 2.20 Chemoselective Diels-Alder reaction with acrolein and ethyl vinyl ketone Catalyst...

Figure 1.2. Endo and exo pathway for the Diels-Alder reaction of cyclopentadiene with methyl vinyl ketone. As was first noticed by Berson, the polarity of the endo activated complex exceeds that of the exo counterpart due to alignment of the dipole moments of the diene and the dienophile K The symmetry-allowed secondary orbital interaction that is only possible in the endo activated complex is usually invoked as an explanation for the preference for endo adduct exhibited by most Diels-Alder reactions.

Tire results of a study of the effect of these catalysts on the model Diels-Alder reaction of methyl vinyl ketone (4.8) with cyclopentadiene (4.6) are summarised in Table 4.1... 

For example, the Diels-Alder reaction of A-benzyl-3-carboxamido-1,6-dihydro-pyridine (14a) andlV-benzyl-3-cyano-l,6-dihydropyridine (14b) with methyl vinyl ketone yielded isoquinuclidines 15a and 15b, respectively, which can be converted into ibogamine alkaloid (16). 

It is believed that clay minerals promote organic reactions via an acid catalysis [2a]. They are often activated by doping with transition metals to enrich the number of Lewis-acid sites by cationic exchange [4]. Alternative radical pathways have also been proposed [5] in agreement with the observation that clay-catalyzed Diels-Alder reactions are accelerated in the presence of radical sources [6], Montmorillonite K-10 doped with Fe(III) efficiently catalyzes the Diels-Alder reaction of cyclopentadiene (1) with methyl vinyl ketone at room temperature [7] (Table 4.1). In water the diastereoselectivity is higher than in organic media in the absence of clay the cycloaddition proceeds at a much slower rate. 

Table 4.1 Diels-Alder reactions of cyclopentadiene (1) with methyl vinyl ketone catalyzed by Fe(II)-K-10 montmorillonite in various solvents...

The Diels-Alder reactions of cyclopentadiene with methyl vinyl ketone and acrylonitrile are accelerated when carried out in water in the presence of jS-CD but are slower with a-CD [65a] (Scheme 4.16). This is in agreement with the observation that the transition states of these cycloadditions fit into the hydro-phobic cavity of P-CD but not in the smaller a-CD cavity. 

Rideout and Breslow first reported [2a] the kinetic data for the accelerating effect of water, for the Diels Alder reactions of cyclopentadiene with methyl vinyl ketone and acrylonitrile and the cycloaddition of anthracene-9-carbinol with N-ethylmaleimide, giving impetus to research in this area (Table 6.1). The reaction in water is 28 to 740 times faster than in the apolar hydrocarbon isooctane. By adding lithium chloride (salting-out agent) the reaction rate increases 2.5 times further, while the presence of guanidinium chloride decreases it. The authors suggested that this exceptional effect of water is the result of a combination of two factors the polarity of the medium and the... 

The aqueous medium also has beneficial effects on the diastereoselectivity of the Diels-Alder reactions. The endo addition that occurs in the classical cycloadditions of cyclopentadiene with methyl vinyl ketone and methyl acrylate is more favored when the reaction is carried out in aqueous medium than when it is performed in organic solvents (Table 6.4) [2b, c]. 

Indium trichloride [30] and methylrhenium trioxide [31] catalyze the aqueous Diels-Alder reaction of acrolein and acrylates with cyclic and open-chain dienes. Some examples of the cycloaddition of methyl vinyl ketone with 1,3-cyclohexadiene are reported in Scheme 6.18. MeReOs does not give satisfactory yields for acroleins and methyl vinyl ketones with substituents at the jS-position and favors the self-Diels-Alder reaction of diene. 

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