Diels-Alder reaction Diene complexes

Lewis acid catalysts increase the reactivity of dienophiles in Diels-Alder reactions by complexing to basic sites on the dienophile. ° The Lewis acid lowers the LUMO of the adjacent ir-system, which strengthens the overlap between the LUMO of the dienophile and the HOMO of the diene. In 1979 Scheeren reported that ZnCh catalyzes the cyclocondensation reaction of unactivated aldehydes with l-methoxy-3-(trimethylsilyloxy)-l,3-butadiene. Experimental details of this reaction, however, were not fully documented. In 1982 Scheeren also reported the use of aluminum alkoxydichlorides as catalysts... 

Hetero-Diels—Alder reaction. The complex formed on treatment of BINOL with j-Bu2Mg shows excellent performance in catalyzing enantioselective cycloaddition of Danishefsky s diene with aldehydes to give 2,3-dihydro-4ff-pyran -ones. ... 

Keywords Birch reduction Diels-Alder reaction Dienes Dienophiles Dimerization Ionic hydrogenation Oxidation Reduction Reductive desulfurization Thiophene 1,1-dioxides Thiophene 1-oxides Transition metal complexes... 

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.

In 1961 Berson et al. were the first to study systematically the effect of the solvent on the endo-exo selectivity of the Diels-Alder reaction . They interpreted the solvent dependence of the endo-exo ratio by consideririg the different polarities of the individual activated complexes involved. The endo activated complex is of higher polarity than the exo activated complex, because in the former the dipole moments of diene and dienophile are aligned, whereas in the latter they are pointing in... 

The mechanism by which Lewis-acids can be expected to affect the rate of the Diels-Alder reaction in water is depicted in Scheme 2.6. The first step in the cycle comprises rapid and reversible coordination of the Lewis-acid to the dienophile, leading to a complex in which the dienophile is activated for reaction with the diene. After the irreversible Diels-Alder reaction, the product has to dissociate from the Lewis-acid in order to make the catalyst available for another cycle. The overall... 

In summary, when using a ligand catalyst ratio of 1.75 1 at pH 5-6 the enantioselectivity of the Diels-Alder reaction between 3.8c and 3.9 is dictated by the activated complexes involving ligand, copper(ir) ion, dienophile and diene. Considering that four different products are formed in this reaction (see Scheme 3.5), at least four different activated complexes are involved However, each of these complexes hus two degrees of freedom that determine the stereochemical outcome of the... 

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). 

In most of the successful Diels-Alder reactions reported, dienes containing no heteroatom have been employed, and enantioselective Diels-Alder reactions of multiply heteroatom-substituted dienes, e.g. Danishefsky s diene, are rare, despite their tremendous potential usefulness in complex molecular synthesis. Rawal and coworkers have reported that the Cr(III)-salen complex 15 is a suitable catalyst for the reaction of a-substituted a,/ -unsubstituted aldehydes with l-amino-3-siloxy dienes [21] (Scheme 1.28, Table 1.12). The counter-ion of the catalyst is important and good results are obtained in the reaction using the catalyst paired with the SbFg anion. 

Yamamoto et al. have developed a catalytic enantioselective carbo-Diels-Alder reaction of acetylenic aldehydes 7 with dienes catalyzed by chiral boron complexes (Fig. 8.10) [23]. This carbo-Diels-Alder reaction proceeds with up to 95% ee and high yield of 8 using the BLA catalyst. The reaction was also investigated from a theoretical point of view using ab-initio calculations at a RHF/6-31G basis set. 

The mechanism for the hetero-Diels-Alder reaction of benzaldehyde 9 with the very reactive diene, Danishefsky s diene 10, catalyzed by aluminum complexes has been investigated from a theoretical point of view using semi-empirical calculations [27]. The focus in this investigation was to address the question if the reaction proceeds directly to the hetero-Diels-Alder adduct 11, or if 11 is formed via a Mukaiyama aldol intermediate (Scheme 8.4) (see the chapter dealing with hetero-Diels-Alder reactions of carbonyl compounds). 

The Diels-Alder reaction of activated olefins is considered as one of the most useful and predictable reactions in organic synthesis. The electron-acceptor character of the pentacarbonylmetal fragment makes a,/J-unsaturated carbene complexes ideal substrates for the [4S+2C] cycloaddition reaction with dienes. 

The Diels-Alder reaction of simple alkoxy alkenylcarbene complexes leads to mixtures of endo and exo cycloadducts, with the endo isomer generally being the major one [96,97]. Asymmetric examples of endo Diels-Alder reactions have also been reported by the use of chiral auxiliaries both on the carbene complex and the diene. Thus, the reaction of cyclopentadiene with chiral alkenylcarbene complexes derived from (-)-menthol proceeds to afford a 4 1... 

Alkoxy alkynylcarbene complexes undergo Diels-Alder reactions with neutral and electron-rich dienes [36f, 104] and also with 1-aza- and 2-aza-l,3-butadi-ene derivatives [84a, 105] (Scheme 57). 

Intermolecular [4C+2S] cycloaddition reactions where the diene moiety is contained in the carbene complex are less frequent than the [4S+2C] cycloadditions summarised in the previous section. However, 2-butadienylcarbene complexes, generated by a [2+2]/cyclobutene ring opening sequence, undergo Diels-Alder reactions with typical dienophiles [34,35] (Scheme 59). Also, Wulff et al. have described the application of pyranylidene complexes, obtained by a [3+3] cycloaddition reaction (see Sect. 2.8.1), in the inverse-electron-demand Diels-Alder reaction with enol ethers and enamines [87a]. Later, this strategy was applied to the synthesis of steroid-like ring skeletons [87b] (Scheme 59). 

Carbene complexes which have an all-carbon tether between the diene and the dienophile react via intramolecular Diels-Alder reaction to give the corresponding bicyclic compound. The stereoselectivities of these reactions are comparable to those observed for the Lewis acid-catalysed reactions of the corresponding methyl esters and much higher than those of the thermal reactions of the methyl esters which are completely unselective. Moreover, the ris-sub-stituted complexes undergo endo-selective reactions where the corresponding reaction of the ester fails [109] (Scheme 61). 

The selectivity for two-alkyne annulation can be increased by involving an intramolecular tethering of the carbene complex to both alkynes. This was accomplished by the synthesis of aryl-diynecarbene complexes 115 and 116 from the triynylcarbene complexes 113 and 114, respectively, and Danishefsky s diene in a Diels-Alder reaction [70a]. The diene adds chemoselectively to the triple bond next to the electrophilic carbene carbon. The thermally induced two-alkyne annulation of the complexes 115 and 116 was performed in benzene and yielded the steroid ring systems 117 and 118 (Scheme 51). This tandem Diels-Alder/two-alkyne annulation, which could also be applied in a one-pot procedure, offers new strategies for steroid synthesis in the class O—>ABCD. 

Diels-Alder reaction of fullerenes with complex dienes type 52 (Figure 2.6) which have a 2,3-bis-(methylene) bicyclo[2.2.2]octane unit [49]. 

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. 

The use of chiral bis(oxazoline) copper catalysts has also been often reported as an efficient and economic way to perform asymmetric hetero-Diels-Alder reactions of carbonyl compounds and imines with conjugated dienes [81], with the main focus on the application of this methodology towards the preparation of biologically valuable synthons [82]. Only some representative examples are listed below. For example, the copper complex 54 (Scheme 26) has been successfully involved in the catalytic hetero Diels-Alder reaction of a substituted cyclohexadiene with ethyl glyoxylate [83], a key step in the total synthesis of (i )-dihydroactinidiolide (Scheme 30). 

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