Cationic Diels-Alder reaction

The most effective Lewis-acid catalysts for the Diels-Alder reaction are hard cations. Not surprisingly, they coordinate to hard nuclei on the reacting system, typically oxygen atoms. Consequently, hard solvents are likely to affect these interactions significantly. Table 1.4 shows a selection of some solvents ranked according to their softness. Note that water is one of the hardest... 

In this section the influence of micelles of cetyltrimethylammonium bromide (CTAB), sodium dodecylsulfate (SDS) and dodecyl heptaoxyethylene ether (C12E7) on the Diels-Alder reaction of 5.1a-g with 5.2 in the absence of Lewis-add catalysts is described (see Scheme 5.1). Note that the dienophiles can be divided into nonionic (5.1a-e), anionic (5.If) and cationic (5.1g) species. A comparison of the effect of nonionic (C12E7), anionic (SDS) and cationic (CTAB) micelles on the rates of their reaction with 5.2 will assess of the importance of electrostatic interactions in micellar catalysis or inhibition. 

The effect of micelles of SDS, CTAB and C12E7 on the apparent second-order rate constants of the Diels-Alder reaction between nonionic 5.1a, anionic 5.1 f and cationic 5.1g with 5.2 is reported in Table 5.1. These apparent rate constants are calculated from the observed pseudo-first-order rate constants by dividing the latter by the overall concentration of 5.2. 

The Diels-Alder reaction of dienophiles 5.1a-e, containing neutral, cationic or anionic substituents, with diene 5.2 in the absence of Lewis acids is retarded by micelles of CTAB, SDS and C12E7. In the situation where the dienophile does not bind to the micelle, the reaction is inhibited because uptake of... 

Ring expansion of five- to six-membered rings such as oxazole —> pyridine derivatives via a Diels-Alder reaction is a well-established procedure. However, the conversion of a six-membered heterocycle into a five-membered ring system has not been exploited to any great extent, and those systems that have been studied usually involve a cationic species. 

Silver trifluoroacetate is a suitable catalyst for various cationic rearrangements involving multiple carbon-carbon bonds [49 5(1] In the presence of silver trifluoroacetate, 2 propynyl acetates rearrange to the butadienyl acetates to give dienes that are useful in Diels-Alder reactions [49] (equation 22)... 

Kiindig et al. recently applied the same perfluoroaryldiphosphonite ligand to the preparation of a cationic Ru catalyst 14 [20] (Scheme 1.27, Table 1.11). This catalyst also promotes the Diels-Alder reaction of a-bromoacrolein and cyclopenta-diene, although this Diels-Alder reaction is slower than that catalyzed by the analogous cationic Fe complex 13, and gives the cycloadducts with lower enantioselec-tivity (Fe 97% ee, Ru 92% ee). 

The cationic aqua complexes prepared from traws-chelating tridentate ligand, R,R-DBFOX/Ph, and various transition metal(II) perchlorates induce absolute enantio-selectivity in the Diels-Alder reactions of cyclopentadiene with 3-alkenoyl-2-oxazoli-dinone dienophiles. Unlike other bisoxazoline type complex catalysts [38, 43-54], the J ,J -DBFOX/Ph complex of Ni(C104)2-6H20, which has an octahedral structure with three aqua ligands, is isolable and can be stored in air for months without loss of catalytic activity. Iron(II), cobalt(II), copper(II), and zinc(II) complexes are similarly active. 

The FMOs of acrolein to the left in Fig. 8.2 are basically slightly perturbed butadiene orbitals, while the FMOs of protonated acrolein resemble those of an allyl cation mixed in with a lone-pair orbital on the oxygen atom (Fig. 8.2, right). Based on the FMOs of protonated acrolein, Houk et al. [2] argued that the predominant interaction in a normal electron-demand carbo-Diels-Alder reaction is between the dienophile LUMO and diene HOMO (Fig. 8.1, left). This interaction is greatly... 

Honk et al. concluded that this FMO model imply increased asynchronicity in the bond-making processes, and if first-order effects (electrostatic interactions) were also considered, a two-step mechanisms, with cationic intermediates become possible in some cases. It was stated that the model proposed here shows that the phenomena generally observed on catalysis can be explained by the concerted mechanism, and allows predictions of the effect of Lewis acid on the rates, regioselectivity, and stereoselectivity of all concerted cycloadditions, including those of ketenes, 1,3-dipoles, and Diels-Alder reactions with inverse electron-demand [2],... 

Diels-Alder reactions Neutral ionic liquids have been found to be excellent solvents for the Diels-Alder reaction. The first example of a Diels-Alder reaction in an ionic liquid was the reaction of methyl acrylate with cyclopentadiene in [EtNH3][N03] [40], in which significant rate enhancement was observed. Howarth et al. investigated the role of chiral imidazolium chloride and trifluoroacetate salts (dissolved in dichloromethane) in the Diels-Alder reactions between cyclopentadiene and either crotonaldehyde or methacroline [41]. It should be noted that this paper describes one of the first examples of a chiral cationic ionic liquid being used in synthesis (Scheme 5.1-17). The enantioselectivity was found to be < 5 % in this reaction for both the endo (10 %) and the exo (90 %) isomers. 

Conjugated cations, anions and radicals can give the Diels-Alder reaction. In such a case, the two cr bonds are formed in two separate steps (stepwise... 

Extensive studies by Gorman and Gassman have shown that an allyl cation can be a 27r-electron component in a normal electron-demand cationic Diels-Alder reaction and, since a carbocation is a very strong electron-withdrawing group, the allyl cation is a highly reactive dienophile [19a, 21]. 

Radical Diels-Alder reactions have been used mainly to synthesize polycyclic molecules. These reactions, like those that involve cations and anions as components, proceed quickly but generally do not give high yields. Thus, the tricyclic enone 14 is the result of an intramolecular Diels-Alder reaction of quenched vinyl radical intermediate 13 obtained by treating the iododienynone 12 with n-tributyltin hydride/2,2 -azobisisobutyronitrile (AIBN) [28] (Equation 1.11). 

The first studies on cation-radical Diels-Alder reactions were undertaken by Bauld in 1981 who showed [33a] the powerful catalytic effect of aminium cation radical salts on certain Diels-Alder cycloadditions. For example, the reaction of 1,3-cyclohexadiene with trans, iraw5-2,4-hexadiene in the presence of Ar3N is complete in 1 h and gives only the endo adduct (Equation 1.14) [33]. 

As a continuation of these studies, Bauld recently reported evidence of a stepwise mechanism in the cation-radical Diels-Alder reaction of phenyl vinyl sulfide with cyclopentadiene [34, 35] (Scheme 1.6). 

The cationic moiety attached to the carbon-carbon double bond is a strong electron-withdrawing group that increases the dienophilic character of the double bond in the Diels Alder reaction. 

Dimethoxyethylacrylate (94) may be readily converted into the cationic species 95 by the action of Lewis acids [92] (Equation 3.32) the cationic species then undergoes Diels Alder reaction with a variety of dienes. The type of catalyst markedly affects the reaction yield, stereoselectivity and regioselectivity as shown in Scheme 3.19 and Equation 3.33. 

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. 

Luche and coworkers [34] investigated the mechanistic aspects of Diels-Alder reactions of anthracene with either 1,4-benzoquinone or maleic anhydride. The cycloaddition of anthracene with maleic anhydride in DCM is slow under US irradiation in the presence or absence of 5% tris (p-bromophenyl) aminium hexachloroantimonate (the classical Bauld monoelectronic oxidant, TBPA), whereas the Diels Alder reaction of 1,4-benzoquinone with anthracene in DCM under US irradiation at 80 °C is slow in the absence of 5 % TBPA but proceeds very quickly and with high yield at 25 °C in the presence of TBPA. This last cycloaddition is also strongly accelerated when carried out under stirring solely at 0°C with 1% FeCh. The US-promoted Diels Alder reaction in the presence of TBPA has been justified by hypothesizing a mechanism via radical-cation of diene, which is operative if the electronic affinity of dienophile is not too weak. 

Photo-induced Diels Alder reaction occurs either by direct photo activation of a diene or dienophile or by irradiation of a photosensitizer (Rose Bengal, Methylene Blue, hematoporphyrin, tetraphenylporphyrin) that interacts with diene or dienophile. These processes produce an electronically excited reagent (energy transfer) or a radical cation (electron transfer) or a radical (hydrogen abstraction) that is subsequently trapped by the other reagent. 

Acetylchloride is a trapping agent that allows the reaction to go completion, transforming the product into a less oxidizable compound.The results of other reactions between indole (57) and substituted cyclohexa-1,3-dienes show that the photo-induced Diels-Alder reaction is almost completely regioselective. In the absence of 59 the cycloaddition did not occur the presence of [2+2] adducts was never detected. Experimental data support the mechanism illustrated in Scheme 4.14. The intermediate 57a, originated from bond formation between the indole cation radical and 58, undergoes a back-electron transfer to form the adduct 60 trapped by acetyl chloride. 

The coupling photolysis Lewis acid is also sometimes effective in promoting a Diels-Alder reaction. Thus, cationic (R,S)-(ON)Ru-salen homochiral complex 71 catalyzed the Diels-Alder reaction between Danishefsky s diene and benzaldehyde when the reagents were exposed to direct sunlight through a window or to incandescent light in t-butyl methyl ether (TBME)[49] (Equation 4.8). The reaction in the dark was very slow and only 3 % ee was detected. 

Different results were obtained by Kobayashi and colleagues [76] performing the Diels-Alder reaction of 2,3-dimethyl butadiene with N-butylmaleimide in water in the presence of various dodecyl sulfate (DS) and dodecane sulfonate (DCS) LASCs [M(DS) M = Sc, Cu n = 3, 2 M(DCS) M = Sc, Yb, Mn, Co, Cu, Zn, Na, Ag n = 3,2, 1]. Unexpectedly, no acceleration was observed with respect to the reactions carried out in water only, and no catalytic effect was found also by using a bidentate dienophile which, in principle, should be able to coordinate the metal cation in the LASC system. 

Gassman [92] has been a pioneer of ionic Diels-Alder reactions that proceed via in situ generation of cationic species (allylic cations) from olefinic precursors... 

Saito N., Grieco P. A. Development of Cationic Diels-Alder Reaction in Highly Polar Media and Total Syntheses of Natural Products Yuki Gosei Kagaku Kyo-kaishi 2000 58 39-49... 

Keywords cationic Diels-Alder reaction, asymmetric synthesis, stereoselective Diels-Alder reaction... 

The suprafacial thermal addition of an allylic cation to a diene (a [3 -f- 4] cycloaddition) is allowed by the Woodward-Hoflfmann rales (this reaction would be expected to follow the same rules as the Diels-Alder reaction ). Such cyclo-... 

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