Diels -Alder reaction with Danishefsky diene

For these, several chiral Lewis acid catalysts, which have the C-2 symmetry element, were designed and tested for various asymmetric syntheses, and in 1985 we reported a zinc reagent and in 1988 a bulky aluminum reagent (Scheme 8) [15, 16]. The zinc reagent was used for asymmetric cyclization of unsaturated aldehyde and the aluminum catalyst for asymmetric hetero-Diels-Alder reaction with Danishefsky diene. Both catalysts effectively discriminate the enantioface of aldehydes for reactions. 

The montmorillonite KlO-catalyzed aza-Diels-Alder reaction of Danishefsky s diene with aldimines, generated in situ from aliphatic aldehydes and p-anisidine, proceeded smoothly in H20 or in aqueous CH3CN to afford 2-substituted 2,3-dihydro-4-pyridones in excellent yields (Eq. 12.47).115 Also, complex [(PPh3)Ag(CBiiH6Br6)] was shown to be an effective and selective catalyst (0.1 mol% loading) for a hetero-Diels-Alder reaction with Danishefsky s diene and the reaction showed a striking dependence on the presence of trace amounts of... 

A similar enantiomer-selective activation has been observed for aldol " and hetero-Diels-Alder reactions.Asymmetric activation of (R)-9 by (/f)-BINOL is also effective in giving higher enantioselectivity (97% ee) than those by the parent (R)-9 (91% ee) in the aldol reaction of silyl enol ethers (Scheme 8.12a). Asymmetric activation of R)-9 by (/f)-BINOL is the key to provide higher enantioselectivity (84% ee) than those obtained by (R)-9 (5% ee) in the hetero-Diels-Alder reaction with Danishefsky s diene (Scheme 8.12b). Activation with (/ )-6-Br-BINOL gives lower yield (25%) and enantioselectivity (43% ee) than the one using (/f)-BINOL (50%, 84% ee). One can see that not only steric but also electronic factors are important in a chiral activator. 

The related 5-trifluoromethyl-l,3-dioxin-4-ones underwent high pressure Diels-Alder reactions with Danishefsky s diene (Eq. 114), and [2 + 2] photocycloadditions with alkenes [305]. The former reaction failed entirely when attempted in the absence of the fluorine atoms. 

Recently, Fukuzumi et al. reported the photochemical Diels-Alder reaction with Danishefsky s diene [252], A mixture of C6o and the stereochemically defined (lii,3Z)-l,4 disubstituted Danishefsky s diene 77 was irradiated for 9h at -30°C to avoid the thermal reaction (Scheme 30). A high pressure mercury lamp... 

A DFT study of the polar Diels-Alder reaction of 4-aza-6-nitrobenzofuroxan with cyclopentadiene found only one highly asynchronous transition state structure associated with the formation of the 4 + 2-adduct.178 4-Nitrobenzodifuroxan has been shown to be a highly reactive nitroalkene in Diels-Alder reactions with common dienes (cyclopentadiene) to produce stable NED adducts and with ethyl vinyl ether to produce IED adducts.179 Unlike a-acylfuran, 2-nitrofurans have been shown to be active dienophiles in thermal NED Diels-Alder reactions with a variety of buta-1,3-dienes, including Danishefsky s diene.180... 

Hetero Diels-Alder reactions with imino dienophiles have been employed as key step in several syntheses of naturally occuring alkaloids. With regard to stereoselective transformations, the approach to (S)-anabasin worked out by Kunz et al. impressively illustrates the high utility of natural carbohydrates as source of chirality in asymmetric synthesis [505]. The N-galactosyl imine 7-28 underwent a Lewis acid catalysed aza Diels-Alder reaction with Danishefsky s diene which proceeded with excellent induced diastereoselectivity to yield the adduct 7-29. A short sequence then afforded the desired alkaloid 7-30. This work also deals with the suitability of several other dienes and imino dienophiles for such transformations (Fig. 7-7). 

Another approach to hydrophenanthrenones and mono- and di-substituted phenanthrenes, based on Diels-Alder reaction between Danishefsky diene (13) and 1-nitronaphthalene (14), has been developed by Mancini et When 1-nitronaphthalene (14) interacts with the electron-rich diene 13 under high pressure, the cycloaddition occurs at a lower temperature and, after aromatization, allows 2-hydroxyphenanthrene (15) to be prepared (Scheme 7.4). 

Similarly, the ethoxycarbonyl-protected 2-nitroindole derivative 57a also participated in Diels-Alder reactions with Danishefsky s diene (52), as well as Rawal s diene (59), to produce the 3-hydroxycarbazole products 58a and 60a in synthetically useful yields (Scheme 16). However, the sulfonyl-protected analog 57b did... 

Interestingly, when the same indole-3-carboxaldehyde derivative 65 is subjected to Diels-Alder reactions with Danishefsky s diene (52), either under thermal or hyperbaric activation, it is the aldehyde and not the indole carbon-carbon double bond that serves as the dienophilic component (Scheme 19) [34]. The hetero-Diels-Alder reaction with the carboxaldehyde proceeded at quantitative conversion (82% yield) under thermal conditions (12 equiv Danishefsky s diene, 170°C, 24 h) and provided the cycloadduct 69 in quantitative yield under hyperbaric conditions (12 equiv Danishefsky s diene, 45°C, 96 h, 12 kbar). 

The other recent examples of asymmetric syntheses involving Danishefsky s diene focused on hetero Diels-Alder reactions. Shibasaki and Feng separately reported asymmetric reactions with carbonyl dienophiles. Shibasaki demonstrated successful asymmetric reactions of ketones using a chiral Cu(I)-Walphos catalyst. Feng used a chiral A,iV -dioxide/In(OTf)3 catalyst in asymmetric cycloaddition reactions of aldehydes. Imine dienophiles are also amenable to asymmetric Diels-Alder reactions with Danishefsky s diene. Wulff reported enantioselective reactions using a VAPOL-B(OPh)3 catalyst system, while Snapper and Hoveyda disclosed silver-catalyzed enantioselective aza Diels-Alder reactions. ... 

Recently, Fukuzumi et al. reported the photochemical Diels-Alder reaction with Danishefsky s diene. 

Bronsted acid catalyzed aza-Diels-Alder reaction of Danishefsky s diene with aidimine generated in situ from aldehyde and amine in aqueous media [107]... 

Danshefsky s diene [19] is the 1,3-butadiene with amethoxy group at the 1-position and a trimethylsiloxy group at the 3-position (Scheme 18). This diene and Lewis acids extended the scope of hetereo-Diels-Alder reactions with aldehydes [20], This diene reacts with virtually any aldehyde in the presence of Lewis acids whereas dienes usually react with only selected aldehydes bearing strongly electron accepting a-substituents. There are two (Diels-Alder and Mukaiyama aldol) reaction pathways (Scheme 18) identified for the Lewis acids catalyzed reactions of Danishefsky diene with aldehydes [21, 22]. The two pathways suggest that these reactions occur on the boundary between the delocahzation band (the pericyclic... 

Bis(trifluoromethanesulfonylamides) ligand was also used by Mikami et al., in 1995, for the lanthanide-catalysed hetero-Diels-Alder reaction of Danishefsky s diene with butyl glyoxylate. This reaction produced the corresponding... 

Similar aza-Diels-Alder reactions of Danishefsky s diene with imines or aldehydes and amines in water took place smoothly under neutral conditions in the presence of a catalytic amount of an alkaline salt such as sodium triflate or sodium tetraphenylborate to afford dihydro-4-pyridones in high yields (Eq. 12.49).117 Antibodies have also been found to catalyze hetero-Diels-Alder reactions.118... 

Schaus et al.41 have also reported an asymmetric hetero Diels-Alder reaction of Danishefsky s diene 10042 with aldehyde 101 catalyzed by chromium(III) complex 99 bearing a similar chiral salen ligand. Product 102 is obtained in moderate to good yield and stereoselectivity (Scheme 5-31 and Table 5-5). 

The ionic liquid [bmim][BF ] is known to catalyze the aza-Diels-Alder reaction in the synthesis of pyrano- and furanoquinolines [190]. This reaction was also catalyzed by the enantiopure bis-imidazolinium salt 67 in 67% yield with an endo. exo ratio of 60 40 (Scheme 69) [191]. The product was obtained as a race-mate. In addition the aza-Diels-Alder reaction with imines and Danishefsky s diene was catalyzed by the salt 67 giving racemic product. The salt and its analogues could be easily prepared via the oxidation of the corresponding aminals [192]. Investigation of the influence of the counter anion in achiral C2-substituted imidazolinium salts, which can be also described as 4,5-dihydroimidazolium or saturated imidazolium salts, in the aza-Diels-Alder reaction showed, that the catalytic activity increased, the more lipophilic the counter anion and therefore the more hydrophobic the salt was [193]. 

Although several Lewis acids are known to catalyze the hetero-Diels-Alder reaction involving imino-dienes or imino-dienophiles (aza-Diels-Alder reaction), a large amount of the catalyst is often necessary. Bi(0Tf)3-xH20 showed higher activity than lanthanide triflates in catalyzing the reactions of imines with Danishefsky s diene (Scheme 15) [72]. 

TADDOL-Promoted Enantioselective Hetero-Diels-Alder Reaction of Danishefsky s Diene with Benzaldehyde-Another Example for Catalysis by Cooperative Hydrogen Bonding... 

Activated dienes such as Danishefsky s diene 112 can also be used in the hetero-Diels-Alder reaction with alkyl glyoxylates. Ghosh and co-workers showed that this reaction proceeded to form cycloadducts 113a,b in yields up to 76% and ee up to 70% using either bu-box 3, phe-box 6 or inda-box ent-9a. The results are summarized in Table 9.18 (Fig. 9.36). 

TABLE 9.18. HETERO-DIELS-ALDER REACTION OE DANISHEFSKY S DIENE WITH GLYOXYLATE ESTERS"... 

TABLE 9.18 HETERO DIELS-ALDER REACTION OF DANISHEFSKY S DIENE WITH GLYOXYLATE ESTERS, 558... 

The aza-Diels-Alder reaction of Danishefsky s diene with imines provides a convenient method for the synthesis of 2-substituted 2,3-dihydro-4-pyridones, a compound class that has important synthetic applications. Kobayashi and co-workers have studied the reaction in detail using ytterbium (III) triflate as the Lewis acid30. Although the reaction is often run at low temperature (—78°C to 0°C) for a number of hours, we have found that the reaction also worked well at elevated temperatures (150°C) in the microwave for a few minutes (J. Westman and A. Hurynowics, unpublished results) (see Scheme 5.15). The imines could either be preformed prior to the addition of the Danishefsky s diene or the reaction could be performed as a multi-component protocol, where all components were added at once. 

Jacobsen studied the efficiency of a series of chiral (salen)Cr(III)X complex (X = Cl, N 3, F, BF4) for the asymmetric hetero Diels-Alder reaction of Danishefsky s diene with aldehydes. The best result was obtained with the terafluoroborate catalyst [65] (Eq. 8A.41). 

The chiral boron complex prepared in situ from chiral binaphthol and B(OPh)3 is utilized for the asymmetric aza-Diels-Alder reaction of Danishefsky s diene and imines [67] (Eq. 8A.43). Although the asymmetric reaction of prochiral imine affords products with up to 90% ee, the double asymmetric induction with chiral imine by using oc-benzylamine as a chiral auxiliary has achieved almost complete diastereoselectivity for both aliphatic and aromatic aldimines. This method has been successfully applied to the efficient asymmetric synthesis of anabasine and coniine of piperidine alkaloides. 

The reactivity of 47/-benzopyran-4-ones in Diels-Alder reactions is well documented <1987T3075>, and recently high asymmetric induction has been achieved in the reaction of 3-alkoxycarbonyl-substituted chromones with chiral auxiliaries and Danishefsky s diene <1991JOC2058>. It should be noted that 3-formylchromones can react as heterodienes in the stereoselective inverse electron Diels-Alder reaction with enol ethers <1994T11755> to provide a route to pyrano[4,3-A][l]benzopyrans a heterocyclic nucleus which occurs naturally in the fungal metabolite fulvic acid <1984CC1565>. The thermal Diels-Alder reaction of 477-pyran-4-one 405 in the presence of an excess of Danishefsky s diene 404 provided cycloadduct 406 (Equation 32) <1996H(43)745>. 

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