Diels-Alder reactions of cyclopentadiene with dienophile

Diels-Alder reactions.6 The Diels-Alder reaction of cyclopentadiene with dienophiles of the general type CH2=CHR results in endo/exo adducts in the ratio of co. 3 1, and this rcgioselecti vity is not affected by catalysts. The ratio is affected when the reaction is conducted heterogeneously with the dienophile adsorbed on nonactivated surfaces such as A1203, Si02, and cellulose. The most striking effect is shown by methyl acrylate adsorbed on alumina (equation I). 

Quite recently, palladium-phosphinooxazohdine catalysts have been used for asymmetric Diels-Alder reactions in ionic liquids [45]. By screening various counterions of the Pd catalysts and ionic liquids, a combination of cationic Pd-POZ catalyst 31c with ShF counterion and [bmim][BF4] as the ionic liquid was found to be the most effective. The Diels-Alder reaction of cyclopentadiene with dienophile 32 using 31c as a catalyst provided DA adduct 33 with high chemical and optical yields. The catalyst 31c immobilized in [bmimJfBFJ was successfully recycled eight times to give 33 in 89-99% yields and 88-99% ee-values (Scheme 7.12). 

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.

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 chiral catalyst 142 achieves selectivities through a double effect of intramolecular hydrogen binding interaction and attractive tt-tt donor-acceptor interactions in the transition state by a hydroxy aromatic group [88]. The exceptional results of some Diels-Alder reactions of cyclopentadiene with substituted acroleins catalyzed by (R)-142 are reported in Table 4.21. High enantio- and exo selectivity were always obtained. The coordination of a proton to the 2-hydroxyphenyl group with an oxygen of the adjacent B-0 bond in the nonhelical transition state should play an important role both in the exo-endo approach and in the si-re face differentiation of dienophile. 

TABLE 27. Rate constants (M 1 s ) for Diels-Alder reactions of cyclopentadiene with several dienophiles in methanol, water and a, 6-cyclodextrin 12 water solution 125... 

Density functional theory has been used to investigate the Diels-Alder reactions of triazolinedione with s-cis- and. y-fran -butadiene. " Combined quantum mechanics-molecular mechanics calculations have been used to investigate the asymmetric Diels-Alder reaction of cyclopentadiene with the complex dienophiles AICI3-methyl acrylate and methoxyaluminium dichloride-acrolein.Equilibrium constants have been determined for the molecular complexes formed from 1-alkyl-1-(2-naphthyl)ethenes and 1-vinylnaphthalene with TCNE in C1(CH2)2C1 at 27.1 °C ... 

Roelfes and coworkers first assessed the catalytic performance of their DNAzyme in asymmetric Diels-Alder reactions of cyclopentadienes with a dienophile that binds to the Cu(II) center through a pyridyl group. The length of the polymethylene spacer and the R substituent proved to be crucial, both for the enantioselectivity as such and also for the sense of stereoinduction (Figure 29). 

Clearly, dynamical correlation must be included. The first study to obtain a reasonable value for the barrier was the work of Bach, which employed perturbation theory. MP2 lowers the barrier substantially from the HF result unfortunately, it predicts a barrier that is too low, in the range 16-20 kcal mol . MP3 raises the barrio- but predicts now too high a value (27-28 kcal mol ). Finally, MP4 provides very good agreement with experiment, but triples configurations must be included to get this best fit (E values of 22.4-22.8 kcal mol ). Very similar trends were obtained by Jorgensen in his examination of the Diels-Alder reaction of cyclopentadiene with ethylene and related dienophiles. 

Diphenyl-BINOL-derived chiral aluminum reagents are prepared in situ by addition of Ethylaluminum Dichloride or Diethylaluminum Chloride to 3,3 -diphenyl-BINOL. These chiral aluminum reagents promote the enantioselective Diels-Alder reaction of cyclopentadiene with the oxazolidone dienophile (eq 14). Endo products are obtained with a high level of asymmetric induction (>90% ee) however, a stoichiometric amount of the Lewis acid is required. The preparation and use of a C3 symmetric BINOL-derived boronate has been reported (eq 15). BINOL-B(OAr)3 complexes have recently been developed for the asymmetric Diels-Alder reaction with imines (eq 16). ... 

The four possible transition-state structures for the Lewis acid-promoted Diels-Alder reaction of cyclopentadiene with propynal are depicted in Fig. 7. In the chiral Lewis acid-promoted reaction, the enantiomeric excess of an adduct originates in the enantiofacial selectivity of cyclopentadiene, which has prochiral reactive centers. The enantioselective pathway presupposes three characteristics (i) the chiral Lewis acid must sterically shield one enantioface of the coordinated propynal because the open acetylenic jr-face in the chiral catalyst-dienophile complex approaches one face of... 

The chiral triflate complex (ebthi)Ti(OTf)2 has been synthesized by the reaction of the parent dichloride with AgOTf and used to catalyze the Diels-Alder reaction of cyclopentadiene with oxazolidinone-derived dienophiles. The level of asymmetric induction is dramatically affected by solvent polarity and this behavior can be partially explained with reference to the results of variable-temperature NMR studies.1665... 

Oh and Meracz were the first to report asymmetric Diels-Alder reaction in ionic liquids [43]. It has also been shown that Diels-Alder reactions in ionic liquids give unusually high stereoselectivities at room temperature as compared to those in conventional organic solvents, where a low temperature was required to achieve good stereoselectivities. For example, the Diels-Alder reaction of cyclopentadiene and dienophile 25 with Cu(ll)-bisoxazoline complex 24 as catalyst in [dbim][BF4] showed a higher endoselectivity (endo j exo = 93/7) and regioselectivity (26/27 = 96/4) than in CHjCb (endojexo = 79/21, 26/27 = 76/24) (Scheme 7.11). 

Fukuzawa and coworkers reported the rare earth (III) salt-catalyzed asymmetric Diels-Alder reaction of cyclopentadiene with a chiral dienophile in SCCO2 [112]. The Diels-Alder reaction in SCCO2 proceeded rapidly to give the corresponding adducts with higher diastereoselectivities than those in CH2CI2 (Scheme 7.41). 

Diels-Alder reactions of cyclopentadiene with methyl acrylate [19], (-)-menthyl acrylate, or other chiral dienophiles [20-23] catalyzed by cation-exchanged KIO montmorillonites were thoroughly investigated by Mayoral and co-workers. The structures of the chiral dienophiles are depicted in Figure 1. Moderate diastereo-selectivities were obtained with (-)-menthyl acrylate (54 %) and (7 )-f -acryloyl-pantolactone (53 %) in reactions catalyzed by zinc(II)-exchanged KIO montmoril-lonite at —20 °C. 

A diastereoselective Diels-Alder reaction of cyclopentadiene with a chiral dienophile, iV,iV -fumaroyldi[(2/ )-bornane-10,2-sultam], was carried out in scC02. The highest diastereoselectivity (65% conversion and 93% de) is obtained around the critical point (74 bar) at 33 C. Lanthanide triflate catalyzes the reaction of cyclopentadiene and 3-acryloyl-(4S)-isopropyloxazolidin-2-one 21 in SCCO2 to give the endo adduct endo exo = 10 30) with a higher diastereoselectivity (59% de) than in CH2CI2 (38-42% de) (Scheme 36). ... 

The Diels—Alder reaction of cyclopentadiene with a dienophile, shown in Scheme 4, was trialed in a PIL in 1989 using EAN. We believe this was the first reported use of a PIL as the reaction media and catalyst in an organic synthesis reaction. The selectivity toward the endo product compared to the exo product was lower in LAN, with endo/ exo ratios of 6.477.4, compared to 7.4/9.3 in water, and the conversion rate was slower in BAN. However, the key feature was demonstrating that reactions of this type were feasible in PILs. 

Extended Hiickel Theory has been used to calculate an approximate energy surface for the [1,3] sigmatropic rearrangement connecting (171) to (172). The calculated relative ease of the various reaction paths is correlated with both the experimental data and the predictions of orbital symmetry theory. A non-coplanar transition state in the Diels-Alder reaction of cyclopentadiene with maleic anhydride, or with other five-membered cyclic dienophiles of C2 symmetry, is suggested by the relationship between the primary and secondary overlap integrals in the Salem-type analysis of the reaction path. ... 

Maleic anhydride has been used in many Diels-Alder reactions (29), and the kinetics of its reaction with isoprene have been taken as proof of the essentially transoid stmcture of isoprene monomer (30). The Diels-Alder reaction of isoprene with chloromaleic anhydride has been analy2ed using gas chromatography (31). Reactions with other reactive hydrocarbons have been studied, eg, the reaction with cyclopentadiene yields 2-isopropenylbicyclo[2.2.1]hept-5-ene (32). Isoprene may function both as diene and dienophile in Diels-Alder reactions to form dimers. 

Several highly enantioselective Diels-Alder reactions are known for which the di-enophile does not fit any of the above classes. Corey and coworkers applied the chiral aluminum reagent 36 with a C2-symmetric stilbenediamine moiety (videsu-pra) to the Diels-Alder reaction of maleimides as dienophiles [54] (Scheme 1.68). In most asymmetric Diels-Alder reactions the reactants are usually relatively simple dienes such as cyclopentadiene or monosubstituted butadienes, and unsym-... 

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