Range and Preparation of Dienes

Some of the most elegant applications of the intramolecular Diels-Alder reaction have been in the stereocontrolled construction of complex natural products. Illustrations of such applicability are included throughout these two chapters. 

The simplest dienes used in the intramolecular Diels-Alder reaction are acyclic. As with the intermolecular cyclization, E dienes are usually more reactive than Z dienes [6], although with highly activated dienophiles or under forcing conditions the latter can be made to participate in the reaction. This topic is addressed in detail in thie next chapter. 

Many diene-containing synthetic fragments are known [7-13]. Employment of such an off-the-shelf moiety can abbreviate the number of steps required for the preparation of a given triene. 

The need for differentially-substituted dienes has led to the development of a number of methods for diene construction [14-21], A critical consideration in the development or application of such a method is the need to control olefin geometry. 

The proceeding examples have all been monosubstituted at the dienophile end of the diene. An internally disubstituted diene has been observed to take part in the intramolecular Diels-Alder reaction, although only after isomerization to the E isomer [22]. 

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Dihydro-1-vinylnaphthalene (67) as well as 3,4-dihydro-2-vinylnaphtha-lene (68) are more reactive than the corresponding aromatic dienes. Therefore they may also undergo cycloaddition reactions with low reactive dienophiles, thus showing a wider range of applications in organic synthesis. The cycloadditions of dienes 67 and 68 and of the 6-methoxy-2,4-dihydro-1-vinylnaphthalene 69 have been used extensively in the synthesis of steroids, heterocyclic compounds and polycyclic aromatic compounds. Some of the reactions of dienes 67-69 are summarized in Schemes 2.24, 2.25 and 2.26. In order to synthesize indeno[c]phenanthrenones, the cycloaddition of diene 67 with 3-bromoindan-l-one, which is a precursor of inden-l-one, was studied. Bromoindanone was prepared by treating commercially available indanone with NBS [64]. 

Base-induced elimination of sulphinate from homoallylic sulphones , from y-ketosulphones , and from 1,2-bissulphones has been used in synthetic sequences ranging from the preparation of retinoic acid and of its methyl ester , to a novel pentannulation sequence that leads to a range of cross-conjugated dienes , as exemplified by equation (69). The overall yield for the two steps was 63%. 

This effect cannot be explained by simply considering differences in frontier orbital energies. A useful monofluorinated dienophile has been prepared [364] using metallated difluoroenol carbamate chemistry (Eq. 143) cycloaddition occurred smoothly with a range of dienes, and desulfination could be achieved under mild conditions without loss of the fluorine atom. Wakselman and co-workers [365] synthesised a rare competent difluorinated dienophile. Lewis acid catalysed Diels-Alder reaction with furan afforded an acceptable yield of (unfortunately) unstable cycloadduct which decomposed to a phenolic product via a dehydrofluorination reaction, circumscribing its utility (Eq. 144). 

In spite of the high asymmetric induction observed in the Mo-catalyzed ARCM of 1,6-dienes, when 4a and 4b are used in reactions involving 1,7-dienes, inferior asymmetric induction is obtained. For example, as illustrated in Scheme 2, dienes 12 and 13 are not resolved with useful selectivity (krei < 5) when 4a is employed as the catalyst. To address this shortcoming, we took advantage of the modular character of the Mo complexes and prepared a range of chiral complexes as potentially effective catalysts. Accordingly, as depicted in Scheme 2, we... 

For the preparation of Nd-BR with narrow MMDs a catalyst system which comprises five components is applied Nd-salt/electron donor add-itive/aluminum based halide donor/alumoxane/aluminum (hydrido) alkyl. The following additives are recommended in order to improve the solubility of the Nd salt acetylacetone, tetrahydrofuran, pyridine, N,N-dimelhyl-formamide, thiophene, diphenylether, triethylamine, organo-phosphoric compounds and mono- or bivalent alcohols. The catalyst components are prereacted for at least 30 seconds in the temperature range of 20-80 °C and catalyst aging is preferably performed in the presence of a small amount of diene [397,398]. 

The synthesis of electron-deficient diene 285 was achieved by the Stille coupling of P-trifluoromethanesulfonyl-a,P-unsaturated sulfone (284) with a 3-stannyl-a,P-unsaturated ester (283) (Scheme 74).148 Similarly, the preparation of a diverse range of enantiomerically pure 1- and 2-sulfinyl dienes has been achieved via Stille coupling of halovinyl sulfoxides and vinyl stannanes.149,150 Enantiomerically pure 1- and 2-sulfinyl dienes have been used extensively in asymmetric Diels-Alder reactions.111... 

Because of the extensive amount of waste generated in traditional Friedel-Crafts reactions, it is not surprising that this reaction has been studied in RTIL. Early examples included the use of catalytic chloroaluminate ionic liquids. However, the moisture sensitivity of such systems was a drawback. Therefore, water-stable rare-earth Lewis acids, such as Sc(CF3S03)3, have come to be used for these reactions.The same Lewis acid has also been used to catalyse Diels-Alder reactions in RTILs.Interestingly, in this example, the RTIL not only provided a means for recycling the catalyst but also accelerated the rate and improved selectivity. It has also been demonstrated that a moisture stable, Lewis acidic, catalytic ionic liquid could be prepared from choline chloride and zinc dichloride, and that this was an excellent medium for the Diels-Alder reaction. Yields of 90% or more were achieved in reaction times of between 8 min and 5h for a range of dienes and dienophiles. 

BLA 4 (Fig. 5) is one of the best catalysts for the enantio- and earo-selective cycloaddition of a-substituted a,/3-enals with highly reactive dienes such as cyclopen-tadiene. The corresponding reactions of a-unsubstituted a,)8-enals such as acrolein and crotonaldehyde are, however, characterized by low enantioselectivity and/or reactivity. The range of dienophiles that can be used with less reactive dienes is quite limited. The use of arylboronic acid with electron-withdrawing substituents such as [3,5-bis(trifluoromethyl)phenyl]boronic acid in the preparation of BLA greatly enhances... 

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