Diels-Alder cycloaddition, catalytic

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]. 

Collins and co-workers have also reported on an enantioselective catalytic Diels—Alder cycloaddition, in which zirconocene and titanocene bis(triflate) complexes were used as catalysts [104], The influence of the solvent polarity on the observed levels of stereoselectivity is noteworthy. For example, as shown in Scheme 6.34, with 108 as the catalyst, whereas in CH2C12 (1 mol% catalyst) the endo product was formed with 30% ee (30 1 endoxxo, 88% yield), in CH3N02 solution (5 mol% catalyst) the enantioselectivity was increased to 89% (7 1 endoxxo, 85% yield). Extensive 1H and 19F NMR studies further indicated that a mixture of metallocene—dienophile complexes was present in both solutions (-6 1 in CH2C12 and -2 1 in CH3N02, as shown in Scheme 6.34), and that most probably it was the minor complex isomer that was more reactive and led to the observed major enantiomer. For example, whereas nOe experiments led to ca. 5 % enhancement of the CpH proton signals of the same ring when Hb in the minor complex was irradiated, no enhancements were observed upon irradiation of Ha in the major complex. 

Another example, in which the piperidine cycle is generated de novo, exploits a hetero Diels-Alder cycloaddition of 1 -/r-tolylsulfinyl-1,3-penta-diene 91 with benzylnitrosoformate, that generates an oxazine 92 with complete regioselectivity and 7i-facial diastereoselectivity.69 Osmilation of the double bond inserts stereoselectively two hydroxyl groups on the oxazine skeleton, protection and catalytic hydrogenation finally afforded the enantiomerically pure imino sugars 94 (Fig. 38). 

The proposed catalytic cycles for the iminium ion catalysed Diels-Alder cycloaddition and conjugate addition reactions are outlined in Fig. 2. The general principles of these catalytic cycles can be used to understand each of the reactions described within this review which all follow a similar mechanistic pathway. The catalytic cycle consists of three principle steps ... 

Modifications to the architecture of the imidazolidinone catalyst provided the fnryl derivative (20) which proved to be a powerfnl catalyst for the catalytic asymmetric Diels-Alder cycloaddition of simple a,P-unsaturated ketones [50]. Although... 

One of the most compelling features of iminium ion catalysis is the proposed mechanistic rationale for the transformations, which leads to highly predictable reaction outcomes. Despite impressive advances and the plethora of reactions reported efforts to provide a detailed mechanistic understanding of the catalytic cycle are limited. The reported work has focussed on the Diels-Alder cycloaddition and has provided useful indicators that could be used in design of more active catalysts. 

For the synthesis of carazostatin (247), the required arylamine 708 was synthesized starting from 1-methoxycyclohexa-l, 3-diene (710) and methyl 2-decynoate (711). The key step in this route is the Diels-Alder cycloaddition of 710 and 711, followed by retro-Diels-Alder reaction with extrusion of ethylene to give 2-heptyl-6-methoxybenzoate (712). Using a three-step sequence, the methoxy-carbonyl group of compound 712 was transformed to the methyl group present in the natural product. 3-Heptyl-3-methylanisole (713) was obtained in 85% overall yield. Finally, the anisole 713 was transformed to the arylamine 708 by nitration and subsequent catalytic hydrogenation. This simple sequence provides the arylamine 708 in six steps and with 26% overall yield (597,598) (Scheme 5.66). 

Allylic nitro compounds containing a suitable dipolarophile undergo Diels-Alder cycloaddition to alkenes in the presence of tin(lV) chloride affording cyclic nitronic esters (Scheme 16).26 Nitronic ester (59) could not be isolated but spontaneously cyclized to the 5,5-fiised cyclic product (60), isolated in 68% yield. The nitronic esters (61a) and (61b) were isolated from the Diels-Alder reaction and could be separated. Heating (61a) in refluxing benzene afforded the 5,6-fused dipolar cydization product (62a) in 93% (68% overall) yield (61b) likewise afforded (62b) in 62% (11% overall) yield. Either (62a) or (62b) could be converted to the tricyclic lactam (63) by catalytic hydrogenolysis followed by lactamiza-... 

Earlier this year the same group described the preparation of novel imprinted polymers with Diels-Alder cycloaddition capabilities [52], The imprinting system was inspired by the same approach used by Gouvemeur et al. for the preparation of catalytic antibodies for Diels-Alder cycloaddition [53]. The reaction between 1,3-butadiene carbamic acid benzylester (78) and A,lV -dimethylacrylamide (79) to give the corresponding endo- and exo-products (80) was chosen as a target. The imprinted polymer made it possible to enhance 20-fold the rate of the reaction when compared with the background. 

The influence of Lewis acids on the 4 + 2-cycloaddition of (2ft,2/ft)-A,iV/-fumaro-ylbis[fenchane-8,2-sultam] with cyclopentadiene and cyclohexadiene was investigated by IR studies of the sultam compexes with various Lewis acids.101 The first enantios-elective silicon Lewis acid catalyst (91) catalysed the Diels-Alder cycloaddition of methacrolein and cyclopentadiene with 94% ee.102 [A1C13 + 2THF] is a new and efficient catalytic system for the Diels-Alder cycloaddition of a,/9-unsaturated carbonyl compounds with dienes under solvent-free conditions.103 Dendritic copper(II) triflate catalysts with a 2,2 -bipyridine core (92) increased the chemical yields of Diels-Alder adducts.104... 

The aromaticities of symmetry-allowed and -forbidden transition states for electrocyclic reactions and sigmatropic rearrangements involving two, four, and six r-electrons, and Diels-Alder cycloadditions, have been investigated by ab initio CASSCF calculations and analysis based on an index of deviation from aromaticity. The order of the aromaticity levels was found to correspond to the energy barriers for some of the reactions studied, and also to the allowed or forbidden nature of the transition states.2 The uses of catalytic metal vinylidene complexes in electrocycliza-tion, [l,5]-hydrogen shift reactions, and 2 + 2-cycloadditions, and the mechanisms of these transformations, have been reviewed.3... 

The inter- and intramolecular Diels-Alder reactions of furans, and their applications to the synthesis of natural products as well as synthetic materials, were reviewed <1997T14179>. HfCU promoted the endo-seXccuve. inter-molecular Diels-Alder cycloadditions of furans with a,/3-unsaturated esters <2002AGE4079>. The cycloaddition between furan and methacrylate was also achieved under these conditions, providing, however the o-isomer as the major cycloadduct. A catalytic enantioselective Diels-Alder reaction between furan and acryloyl oxazolidinone to provide the < 46i-adduct in 97% ee was achieved by using the cationic bis(4-fer7-butyloxazoline)copper(ll) complex 55, as shown in Equation (41) <1997TL57>. 

Ionic liquids can be used as replacements for many volatile conventional solvents in chemical processes see Table A-14 in the Appendix. Because of their extraordinary properties, room temperature ionic liquids have already found application as solvents for many synthetic and catalytic reactions, for example nucleophilic substitution reactions [899], Diels-Alder cycloaddition reactions [900, 901], Friedel-Crafts alkylation and acylation reactions [902, 903], as well as palladium-catalyzed Heck vinylations of haloarenes [904]. They are also solvents of choice for homogeneous transition metal complex catalyzed hydrogenation, isomerization, and hydroformylation [905], as well as dimerization and oligomerization reactions of alkenes [906, 907]. The ions of liquid salts are often poorly coordinating, which prevents deactivation of the catalysts. 

A domino Knoevenagel/Diels-Alder epimerization sequence followed by Suzuki coupling provided a library of biphenyl and terphenyl spirocychc triones (Scheme 24) [58]. The initial Knoevenagel adducts 103 were formed from either 1,3-indandione or Meldrum s acid 101 and various bromosubstituted benzalde-hydes in the presence of catalytic (l)-5,5-dimethyl thiazolidinium-4-carboxylate (DMTC) in high yields. Diels-Alder cycloaddition of 103 with 104, formed in sim from 102 and (l)-DMTC, provided exclusively the cA-spiro compounds 105 due to epimerization of the minor trans isomer to the thermodynamically more stable cis. Subsequent Suzuki couplings of 105 with various boronic acids afforded the final compounds 106. 

This isolated report encouraged preparation of a host of chiral Lewis acids throughout the world to test their capacity to induce asymmetric Diels-Alder reactions catalytically. However, until very recently vide ir a) only disappointing face selectivities (<50%) were found on [4 + 2] cycloadditions of alkenic ene and dienophile partners. 

Catalytic asymmetric induction in Diels-Alder reactions is somewhat more difTicult to analyze based on these models. The chiral Lewis acids shown in Figure 43 all promote asymmetric Diels-Alder cycloaddition with variable degrees of enantioselectivity. " ... 

The lactone-directed intramolecular Diels-Alder cycloaddition was the key step in D.F. Taber s synthesis of trans-dihydroconfertifolin. During the endgame, the Simmons-Smith cyclopropanation was utiiized to install the gem-dimethyl group at C4. The trisubstituted alkene was cyclopropanated in excellent yield and the resulting cyclopropane was subjected to catalytic hydrogenation. 

Jacobsen reported in 1990 that Mnm complexes of chiral salen ligands (41) were the most efficient catalysts available for the enantioselective epoxidation of alkyl- and aryl-substituted olefins.118 This stimulated a rapid development in the chemistry and applications of chiral SB complexes, which offer promising catalytic applications to several organic reactions, such as enantioselective cyclopropanation of styrenes, asymmetric aziridination of olefins, asymmetric Diels-Alder cycloaddition, and enantioselective ring opening of epoxides.4,119... 

Keywords Catalytic antibody. Hapten, Enantiofacial, Enantioselective, Diels-Alder cycloaddition, Cationic reactions, Aldol condensation. Disfavored cyclization... 

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