Chalcones Diels-Alder reactions

PTAD continues to find extensive use, particularly as a dieneophile, but a variety of other reactions have been reported. Treatment of the chalcone (79) with PTAD gives a mixture of the bis(adducts) (81) and (82) presumably via the intermediate (80) (Scheme 13) <91BCJ3188>. Diels-Alder reactions with a variety of dienes have been reported, giving unexceptional products <85JCS(Pl)71>. 

Among the most intensively investigated of all the chalcone Diels Alder adducts are a group obtained solely from Morus species in which the diene component of the reaction is a dehydroprenylflavanone. The structures of several such compounds published prior to 1992 have now been revised on the basis of new spectroscopic and chemical data. Among the most important of the techniques used were two-dimensional NMR and circular dichroism spectroscopy. The revised structures listed in Table 16.5 are those of sanggenons C (210), D (211), E (212), and O (213). In these compounds, the flavanones show the common feature... 

In search for control of absolute stereochemistry, the reaction of thio-chalcones was investigated with unsaturated amides bearing an Evans chiral oxazolidinone [223] and dimenthyl fumarate [224, 225]. For the first time with thiocarbonyl compounds, the efficiency of Lewis acid addition was demonstrated, and reactions could be conducted at room temperature. With EtAlCl2 (Table 4, entry 2) or A1C13 (entry 3), levels of induction up to 92% were attained for the endo isomer. Yb(OTf)3 in DMSO also caused the acceleration of the reaction with chiral acrylamides with p-facial selectivity [226]. This group has also reported [227] an intramolecular hetero Diels-Alder reaction with divinyl thioketones and the double bond of an allyloxy group (Table 4, entry 4). 

Apart form the aforementioned highly enantioselective hetero-Diels-Alder reactions, that proceed with very low catalyst loadings, the catalytically accessible enolates have also been used for related intramolecular Michael reactions (Philips et al. 2007) and for the desym-metrization of 1,3-diketones yielding cyclopentenes via an intramolecular aldol reaction (Wadamoto et al. 2007). The formation of cyclopentenes, however, presents a special case, so—depending on the stereochemical nature of the enone substrates (s-cis or s-trans) and the stereochemistry of the final products—two different mechanisms are discussed in the literature. Whereas /ran.v-cycl open (cries are proposed to be available upon conjugate addition of a homoenolate to chalcones,... 

Besides Michael additions the mild reaction conditions of CIR are also compatible with cycloadditions. Since chalcones can also be considered as heterodienes, Diels-Alder reactions with inverse electron demand are suitable elementary steps that are applicable for heterocycle synthesis. Therefore, after CIR of electron-deficient (hetero)aryl halides 11 and (hetero)aryl propargyl alcohols 12, (hetero) cyclic and acyclic morpholino enamines 98 are added and, finally, after adding... 

As described above, the stereochemistries of the mulberry Diels-Alder type adducts could be divided into the following two groups one is an all-trans in relative configuration and the other is a cis-trans configuration. All-trans type adduct may correspond to an exo-addition product in the Diels-Alder reaction of a chalcone and a dehydroprenylphenol, whereas a cis-trans type adduct corresponds to an endo-addition product in the reaction. 

Besides those spontaneous processes a variety of [4+2]-cycloadditions exists for which it still remains unclear whether they are Diels-Alder reactions and if so, whether they proceed spontaneously or only in the presence of an enzyme. In this respect the stereospecific synthesis of the sesterpenoid heliocide H2 28, an insecticide isolated from cotton wool, from hemigossypolon 29 and myrcene 30 (Scheme 7) [12, 13] should be mentioned. Other examples of biomolecules which are probably formed by Diels-Alder reactions contain the chalcone kuwanon J 31 from the mulberry tree Moms alba L. [14], the mycotoxins chaetoglobosin A 33... 

The model reaction to be mediated by hybrid catalysts comprised of 32/serum albumins, was the Diels-Alder reaction of the H O-soluble aza-chalcone 33 with cyclopentadiene 34 with formation of chiral adducts 35. This reaction had been originally devised by Engberts [123, 124], who used Cu -complexes of amino acids in aqueous medium ee up to 74%). Later it was employed by Feringa in the study of Cu -conjugates of DNA as catalysts [125]. 

Scheme 7.74 NHC-catalyzed asymmetric formal Diels-Alder reaction of enals and chalcones reported by Chi.

The Chi group disclosed highly enantioseleetive formal hetero-Diels-Alder reactions between chalcones and formyleyelopropanes in 2011. The challenging NHC-bounded enolate intermediates from formyleyelopropanes were captured for new C—C bond-forming reaetions. The produets were obtained with high diastereo- and enantioseleetivity and could be easily transformed to optically pure multisubstituted eyclohexane derivatives (Scheme 7.88). 

Scheme 7.88 NHC-catalyzed formal hetero-Diels-Alder reactions between formyl-cyclopropanes and chalcones reported by Chi.

In order to confirm this deduction and the proposed regioselectivity of the Diels-Alder type reaction between a chalcone and a dehydropren-ylphenol, two model compounds 115 and 116 were prepared in 46% resp. 25% yield by a Diels-Alder reaction between /ra 5-chalcone and 3-methyl-l-phenyl-l,3-butadiene (250 °C, 5h). Their structures were established by X-ray crystallography and are shown in Fig. 24. The H-NMR spectra of 115 and 116 were compared with those of alcohols 117 and 118 obtained by reduction. Signals of the protons on the relevant carbon atoms of alcohols 117 and 118 were shifted by 1.16 ppm and 1.61 ppm to higher field than the corresponding signals in 115 and 116, as shown in Fig. 25. 

Figure 18.2 Diels-Alder reaction of cyclopentadiene with aza-chalcone catalyzed by copper complexes in the presence of DNA [6c,d].

In 2009, Feng and coworkers developed new guanidine catalysts with an amino amide skeleton [139]. Among the various catalysts tested, guanidine 49 was found to be the most active for the enantioselective Michael reaction of a (i-ketoester with nitroolefins (Scheme 10.46). The conjugate addition products were obtained in high yields and excellent diastereo- and enantioselectivities. The same researchers used bis-guanidine catalysts for the enantioselective inverse-electron-demand hetero-Diels-Alder reaction of chalcones with azlactones (Scheme 10.47) [140] and enantioselective Mannich-type reaction of a-isothiocyanato imide and sulfonyl imines (Scheme 10.48) [141]. 

About seventy kinds of new phenolic compounds could be isolated from Japanese cultivated mulberry tree (Morus alba, M. bombycis, and M, Ihou) and Chinese crude drug Sang-Bai-Pi (the root bark of Chinese mulberry tree). Most of them are isoprenylated flavonoids. Among them, kuwanon G (1) was the first isolation of the active substance exhibiting the hypotensive effect from the Japanese Morus alba root bark [9]. Furthermore, kuwanon G (1) and its isoprenylated derivative kuwanon H (2) [10] are considered to be formed through an enzymatic Diels-Alder type reaction of a chalcone and a dehydrokuwanon C or its... 

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