Diels-Alder reaction conditions

The metathetic transformation of enynes in the presence of ruthenium precursors provide conjugated cycloalkenes, which are reactive under Diels-Alder reaction conditions with dienophiles. Many examples of such thermally activated [2 + 4] cycloadditions have been reported in the literature [51-59], and the beneficial effect of a ruthenium catalyst has been shown when the reaction was performed in one pot without isolation of the diene [60]. 

It is well known that simple furans, e.g., furan and 2-methyIfuran, do not react with a,j8-unsaturated aldehydes and ketones under Diels-Alder reaction conditions.163 If the reaction is catalyzed by... 

Diels-Alder reaction Conditions Natural product Ref. 

When conventional Diels-Alder reaction conditions were employed (entries 1 and 2), a chromatographically inseparable mixture of stereoisomers 3.20/3.21 (R = Et) was obtained. Unfortunately, only 3.20 could be used for their proposed synthesis of glaucarubinone. This posed an interesting stereocontrol problem since the formation of both products involved secondary orbital (endo) overlap of the diene with an activating group - the former with the ketone and the latter with the aldehyde. 

Under the usual conditions their ratio is kinetically controlled. Alder and Stein already discerned that there usually exists a preference for formation of the endo isomer (formulated as a tendency of maximum accumulation of unsaturation, the Alder-Stein rule). Indeed, there are only very few examples of Diels-Alder reactions where the exo isomer is the major product. The interactions underlying this behaviour have been subject of intensive research. Since the reactions leadirig to endo and exo product share the same initial state, the differences between the respective transition-state energies fully account for the observed selectivity. These differences are typically in the range of 10-15 kJ per mole. ... 

In the kinetic runs always a large excess of catalyst was used. Under these conditions IQ does not influence the apparent rate of the Diels-Alder reaction. Kinetic studies by UV-vis spectroscopy require a low concentration of the dienophile( 10" M). The use of only a catalytic amount of Lewis-acid will seriously hamper complexation of the dienophile because of the very low concentrations of both reaction partners under these conditions. The contributions of and to the observed apparent rate constant have been determined by measuring k pp and Ka separately. ... 

In summary, the groups of Espenson and Loh observe catalysis of Diels-Alder reactions involving monodentate reactants by Lewis acids in water. If their observations reflect Lewis-acid catalysis, involvirg coordination and concomitant activation of the dienophile, we would conclude that Lewis-acid catalysis in water need not suffer from a limitation to chelating reactants. This conclusion contradicts our observations which have invariably stressed the importance of a chelating potential of the dienophile. Hence it was decided to investigate the effect of indium trichloride and methylrhenium trioxide under homogeneous conditions. 

We chose benzyli dene acetone (4.39, Scheme 4.11) as a model dienophile for our studies. The uncatalysed Diels-Alder reaction of this compound with cyclopentadiene is slow, justifying a catalytic approach. Reaction of 4.39 with paraformaldehyde and dimethyl amine under acidic conditions in an aqueous ethanol solution, following a literature procedure, produced the HCl salt of 4.42 (Scheme 4.11). The dienophile was liberated in situ by adding one equivalent of base. 

Note that for 4.42, in which no intramolecular base catalysis is possible, the elimination side reaction is not observed. This result supports the mechanism suggested in Scheme 4.13. Moreover, at pH 2, where both amine groups of 4.44 are protonated, UV-vis measurements indicate that the elimination reaction is significantly retarded as compared to neutral conditions, where protonation is less extensive. Interestingy, addition of copper(II)nitrate also suppresses the elimination reaction to a significant extent. Unfortunately, elimination is still faster than the Diels-Alder reaction on the internal double bond of 4.44. 

Cyclohexene derivatives can be oxidatively cleaved under mild conditions to give 1,6-dicarbonyl compounds. The synthetic importance of the Diels-Alder reaction described above originates to some extent from this fact, and therefore this oxidation reaction is discussed in this part of the book. 

Under different conditions [PdfOAcj2, K2CO3, flu4NBr, NMP], the 1 3 coupling product 86 with 4-aryl-9,10-dihydrophenanthrene units was obtained. The product 86 was transformed into a variety of polycyclic aromatic compounds such as 87 and 88[83], The polycyclic heteroarene-annulated cyclopen-tadicnc 90 is prepared by the coupling of 3-iodopyridine and dicyclopentadiene (89), followed by retro-Diels Alder reaction on thermolysis[84]. 

The allenyl moiety (2,3-aikadienyl system) in the carbonylation products is a reactive system and further reactions such as intramolecular Diels-Alder and ene reactions are possible by introducing another double bond at suitable positions of the starting 2-alkynyl carbonates. For example, the propargylic carbonate 33 which has l,8(or 1.9)-diene-3-yne system undergoes tandem carbonylation and intramolecular Diels-Alder reaction to afford the polycyclic compound 34 under mild conditions (60 C, 1 atm). The use of dppp as ligand is important. One of the double bonds of the allenyl ester behaves as part of the dieneflSj. 

Scheme 99) (416). The 4-acetyloxy-5-ary]thiazo]e or 4-methoxy-5-arylthiazole, which are models of the protomer (174b) do not give cycloaddition products under the same experimental conditions. This rules out the possibility of a Diels-Alder reaction involving the protomer (174b) (416). 

Ma.nufa.cture. Butenediol is manufactured by partial hydrogenation of butynediol. Although suitable conditions can lead to either cis or trans isomers (111), the commercial product contains almost exclusively iVj -2-butene-l,4-diol Trans isomer, available at one time by hydrolysis of l,4-dichloro-2-butene, is unsuitable for the major uses of butenediol involving Diels-Alder reactions. The Hquid-phase heat of hydrogenation of butynediol to butenediol is 156 kj/mol (37.28 kcal/mol) (112). 

Oxidation of thiophene with peracid under carefully controlled conditions gives a mixture of thiophene sulfoxide and 2-hydroxythiophene sulfoxide. These compounds are trapped by addition to benzoquinone to give ultimately naphthoquinone (225) and its 5-hydroxy derivative (226) (76ACS(B)353). The further oxidation of the sulfoxide yields the sulfone, which may function as a diene or dienophile in the Diels-Alder reaction (Scheme 88). An azulene synthesis involves the addition of 6-(A,A-dimethylamino)fulvene (227) to a thiophene sulfone (77TL639, 77JA4199). 

Further evidence showed this mechanism to be incorrect, especially the fact that it was methyl cinnamate and not (347) which was isolated from the reaction (73CPB2026). Also 1-phenylpyrazoles did not react with DMAD under the reaction conditions (74BSF2547). The origin of (346) remains obscure, but in no circumstances does it imply a Diels-Alder reaction of a pyrazole. For Ogura et al., it has its origin in an intermediate A -pyrazoline (73CPB2026). 

Knunyants showed that such perfluoroalkenes, under forcing conditions, undergo Diels-Alder reactions with cyclic dienes such as cyclohexadiene [72] (equation 65) or furan [7J] (equation 66). 

With few exceptions chiral Lewis acids are usually moisture-sensitive and require anhydrous conditions, but bench-stable aquo complexes such as [Cu(S,S)-t-Bu-box)(H20)2](SbF6)2 were found to promote the Diels-Alder reaction as effectively as the anhydrous copper reagent. 

Below is a table of asymmetric Diels-Alder reactions of a,/ -unsaturated aldehydes catalyzed by chiral Lewis acids 1-17 (Fig. 1.10, 1.11). The amount of catalyst, reaction conditions (temperature, time), chemical yield, endojexo selectivity, and optical purity are listed (Table 1.32). 

The two transition states in Figs 8.5 and 8.6 correspond in principle to a metal-catalyzed carho-Diels-Alder reaction under normal electron-demand reaction conditions and a hetero-Diels-Alder reaction with inverse electron-demand of an en-one with an alkene. The calculations by Houk et al. [6] indicated that with the basis set used there were no significant difference in the reaction course. 

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