Diels-Alder allowed reactions

An ab initio study of the l-azabicyclo[1.1.0]butyl cation (97) and its isomers shows that (98) and (99) are much less stable than (97), and that the transition states between (97), (98), and (99) are too high in energy to allow (99) to form. The 3-halobicyclo[l.l.l]pent-l-yl cation (101) has been shown to be an intermediate in the addition of halogens to (100). The only product observed was (102) no rearranged products were detected. The Diels-Alder-type reaction of (103) to give (104) is said to involve several carbenium ion intermediates. 

An example of the second type of modification is the application of the Diels-Alder cycloaddition reaction to polders and copol ers containing pendant or backbone furan moieties. The use of bis-dienophiles such as propiolic acid and its esters or bis-maleimides provides a means of crosslinking based on multiple bridging by the double interchain lycloadditions. The thermal reversibility of these reactions allows the return to the original linear structure (thermoplastic material) by simply heating the gel. 

Oxamborolidenes. There are noteworthy advances in the design, synthesis, and study of amino acid-derived oxazaborolidene complexes as catalysts for the Mukaiyama aldol addition. Corey has documented the use of complex 1 prepared from A-tosyl (S)-tryptophan in enantioselective Mukaiyama aldol addition reactions [5]. The addition of aryl or alkyl methyl ketones 2a-b proceeded with aromatic as well as aliphatic aldehydes, giving adducts in 56-100% yields and up to 93% ee (Scheme 8B2.1, Table 8B2.1). The use of 1-trimethylsilyloxycyclopentene 3 as well as dienolsilane 4 has been examined. Thus, for example, the cyclopentanone adduct with benzaldehyde 5 (R = Ph) was isolated as a 94 6 mixture of diastereomers favoring the syn diastereomer, which was formed with 92% ee, Dienolate adducts 6 were isolated with up to 82% ee it is important that these were shown to afford the corresponding dihydropyrones upon treatment with trifuoroacetic acid. Thus this process not only allows access to aldol addition adducts, but also the products of hetero Diels-Alder cycloaddition reactions. 

Furans are also useful 4ji components for tandem Ugi condensation/intra-molecular Diels-Alder cascade reactions. For example, stirring a methanolic mixture of compounds 127-129 and benzylamine at rt provided the Ugi condensation product 130 that underwent a subsequent intramolecular Diels-Alder cycloaddition to furnish 131 in 70-90% yield (Scheme 23) (99TL1851). This methodology also allowed for a solid phase synthesis by using an ArgoGel-Rink resin as the amine component, providing cycloadducts 131 (after cleavage from the resin) in ca. 90-95% yields. 

Stronger Brpnsted acid catalysts such as N-triflyl phospho-ramides. N-Triflyl phosphoramides were first apphed to the asymmetric Diels-Alder (DA) reaction of unsaturated ketones with silyloxydienes. While the established phosphoric acids demonstrated no catalytic activity, 5 mol% of N-triflyl phosphoramide 46 proved highly effective for the DA reaction of ethyl vinyl ketone with a range of sily-loxydienes, allowing access to highly enantioenriched endo products in good yields (35 to >99%, 82-92% ee) via a presumed boat transition state such as 47 (Scheme 7). 

Tunca et al. [27, 28,38] reported in a series of papers on a multi-click approach for the preparation of brush copolymers. The backbone consisted of homopolymers, statistical polymers, or block copolymers from ONBEs with orthogonal side groups for Diels-Alder click reaction [27,28,38], azide/alkyne click reaction, [27, 28, 38] and nitroxide coupling [27]. In a grafting-to approach, maleimide-or ONBE-functionalized polymers (PEG, P BA, PMMA (56)) were attached by Diels-Alder click reaction with the anthracene groups pendant at the polymer backbone (55) (Scheme 9.8b). PCL chains were attached by an azide/alkyne click reaction, while a combination of Diels-Alder and azide/alkyne click reaction allowed the synthesis of graft copolymers with PS-/ -PEG-, PS-h-PMMA-, or PS-/ -P BA side chains. 

The Diels-Alder (DA) reaction is classified as a [4 -f 2] and thermally allowed reaction, and the reverse reaction, namely retro-Diels-Alder (rDA) reaction, is also thermally allowed. 

Cascade Diels-Alder/Schmidt reactions [402] allow the synthesis ofpolycycHc compounds, which lead to useful precursors for the synthesis of natural products. Finally, fragmentation reactions can occur, and in some cases the corresponding nitriles are obtained [403],... 

Scheme 1.1. Schematic representation of the Diels-Alder reaction. The versatility of the reaction is illustrated by the fact that heteroatoms are allowed at any of the positions a-f. Structures A and B indicate two regioisomeric products.

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.

Fortunately, azachalcone derivatives (2.4a-g, Scheme 2.4) turned out to be extremely suitable dienophiles for Lewis-add catalysed Diels-Alder reactions with cyclopentadiene (2.5). This reaction is outlined in Scheme 2.4 and a large part of this thesis will be devoted to the mechanistic details of this process. The presence of a chromophore in 2.4 allows kinetic studies as well as complexation studies by means of UV-vis spectroscopy. Furthermore, the reactivity of 2.4 is such that also the... 

Rate constants for the Diels-Alder reaction of 2.4b-e have also been determined. The results are shown in Table 2.3. These data allow an analysis of the influence of substituents on the Lewis-acid catalysed Diels-Alder reaction. This is interesting, since there are indications for a relatively large... 

In a second attempt to extend the scope of Lewis-acid catalysis of Diels-Alder reactions in water, we have used the Mannich reaction to convert a ketone-activated monodentate dienophile into a potentially chelating p-amino ketone. The Mannich reaction seemed ideally suited for the purpose of introducing a second coordination site on a temporary basis. This reaction adds a strongly Lewis-basic amino functionality on a position p to the ketone. Moreover, the Mannich reaction is usually a reversible process, which should allow removal of the auxiliary after the reaction. Furthermore, the reaction is compatible with the use of an aqueous medium. Some Mannich reactions have even been reported to benefit from the use of water ". Finally, Lewis-acid catalysis of Mannich-type reactions in mixtures of organic solvents and water has been reported ". Hence, if both addition of the auxiliary and the subsequent Diels-Alder reaction benefit from Lewis-acid catalysis, the possibility arises of merging these steps into a one-pot procedure. 

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