Diels-Alder reactions of 2-pyrones

Reaction of pyrones under dassical conditions requires the use of high temperatures to obtain low to moderate yields. The Diels-Alder reaction of pyrones has been performed in a commercial microwave oven under solvent-free conditions on solid supports such as silica gel, montmorillonite, fitrol clay and alumina. The reaction time was dramatically reduced - from 4 h to 4 min (Scheme 9.9) [50],... 

Scheme 4. Silica gel-catalyzed Diels-Alder reactions of pyrone derivates.

Professor John K. Stille, one of the outstanding polymer chemists of our time, died on July 19, 1989, in the crash of the United Airlines flight in Sioux City, Iowa. John was educated as a polymer chemist in the illustrious school of G.S. Marval. In that tradition, ability to synthesize novel materials plays a major role. John more than lived up to that tradition. Particularly memorable is his extended work on the polyquinoxalines, important materials in the aerospace industry. Beyond these, he synthesized authentic poly-p-phenylene utilizing Diels-Alder reactions of pyrones, synthesized a new type of polyacetylene by cyclopolymerization, and studied numerous other novel polymers. 

The forth synthetic strategy is to utilize pyrone structure to trigger intramolecular Diels-Alder reaction [30]. In this strategy, we can construct the core structure of Maoecrystal V via compound 1.7.26. As shown in Fig. 1.18, natural product Maoecrystal V can be transformed to compound 1.7.24 via simple functional group transformations, and compound 1.7.24 can be prepared by compound 1.7.25 via ring-opening lactonization. Compound 1.7.25 can be constructed by compound 1.7.26 via intramolecular Diels-Alder reaction of pyrone. The precursor (1.7.26)... 

Diels-Alder reactions of pyrones can be used in a related way. The adducts are unstable toward elimination of carbon dioxide. In the examples shown below, there is a further elimination leading to the aromatic product. 

Development of base-catalyzed Diels-Alder reaction of 3-hydroxy-2-pyrone and its application to synthesis of bioactive compounds 99YGK84. 

Because of their low reactivity, a Diels-Alder reaction of 2-pyrones usually requires such a high temperature that the initial bicyclic lactone adducts often undergo cycloreversion [30,33] with loss of CO2. In some cases this limitation has been overcome by carrying out the reaction imder high pressure conditions. Posner and coworkers have shown [34-36] that the presence of a tolylthio group or a bromine atom at the 3- or 5-position increases the reactivity of 2-pyrones. 3-Bromo-2-pyrone (35) (Scheme 2.15), as well as its regioisomer 5-bromo (36)... 

Table 4.25 Diels-Alder reactions of 3-hydroxy-2-pyrone (145) catalyzed by cinchona alkaloids...

Table 5.4 High pressure Lewis-acid catalyzed Diels-Alder reactions of 2-pyrone 165 with benzylvinylether 166 ...

Okamura H., Iwagawa M. and Nakatani M. Development of Base Catalyzed Diels-Alder Reaction of 3-Hydroxy-2-Pyrone and Application to Synthesis of Biologically Active Compounds Org. Chem. Japan 1999 57 84... 

Marko I. E., Evans G. R., Seres P., Chelle L, Janousek Z. Catalytic, Enantiose-lective, Inverse Electron-Demand Diels-Alder Reactions of 2-Pyrone Derivatives... 

Treatment of bicyclic lactones 66, derived from Diels-Alder reaction of 3-carboxy-2-pyrone under standard radical conditions using (TMSlsSiH, leads to bridged lactones 67, which can smoothly be converted to bicyclo[3.3.0]-lactones 68 (Scheme 10). For X = CHaOMe, this cascade of rearrangements took place in a 78% overall yield, providing 68 in diastereomerically pure form. Three additional steps provided a novel route toward Corey s lactone 69. 

These phenomena can be illustrated by the cycloaddition reactions of fulvenes with electron-deficient a-pyrones. In general, the Diels-Alder reactions of electron-deficient dienes such as 458 with 6-alkyl substituted fulvenes favor addition across one of the endocyclic... 

The intermediate J4 was prepared by an "intramolecular Narasaka type Diels-Alder reaction" of dienophile 10 and 3-hydroxy-2-pyrone (J L) in the presence of phenylboronic acid [7] ... 

Diels-Alder reactions of 2-pyrones are efficient methods towards construction of bridged cyclohexene derivatives for natural product syntheses. Early studies by... 

Okamura and Nakatani [65] revealed that the cycloaddition of 3-hydroxy-2-py-rone 107 with electron deficient dienophiles such as simple a,p-unsaturated aldehydes form the endo adduct under base catalysis. The reaction proceeds under NEtj, but demonstrates superior selectivity with Cinchona alkaloids. More recently, Deng et al. [66], through use of modified Cinchona alkaloids, expanded the dienophile pool in the Diels-Alder reaction of 3-hydroxy-2-pyrone 107 with a,p-unsaturated ketones. The mechanistic insight reveals that the bifunctional Cinchona alkaloid catalyst, via multiple hydrogen bonding, raises the HOMO of the 2-pyrone while lowering the LUMO of the dienophile with simultaneous stereocontrol over the substrates (Scheme 22). 

The a-pyrone (635) undergoes an exothermic Diels-Alder reaction with 1-diethylamino-1-propyne to afford the cycloadduct (636) (77JOC2930). Only a single regioisomer is produced, which is in line with the expected polarization of these reagents (Scheme 144). A Diels-Alder reaction of the same a-pyrone with 1-dibenzylamino-l-propyne affords an aniline derivative which has been employed in a chiral synthesis of the aromatic portion of the ionophore antibiotic lasalocid (80JA6178). 

This procedure describes the preparation and inverse electron demand (LUM0(jjene controlled/ Diels-Alder reaction of an electron-deficient diene. While extensive studies on the preparative utility of the normal (HOMOjjg controlled) Diels-Alder reaction have been detailed, few complementary studies on the preparative value of the inverse electron demand Diels-Alder reaction have been described. Table I details representative 3-carbomethoxy-2-pyrones which have been prepared by procedures similar to that described herein and Tables II and III detail their inverse electron demand Diels-Alder reactions with electron-rich dienophiles. 

A use of the LUM0(j.jene controlled Diels-Alder reactions of 3-carbomethoxy-2-pyrones in the preparation of a full range of oxygenated aromatics [e.g., benzene, 1-, 2-, or 3-phenol, symmetrical and unsymmetrical... 

Table III. Diels Alder Reactions of 3-Carbomethoxy-2-pyrone (ad)61. 

Recently, the reaction of masked ortho-benzoquinone [92] with C60 was tested [93]. The [4+2] cycloaddition reaction of such electron-deficient dienes with fullerenes resulted in the formation of highly functionalized bicyclo [2.2.2] octenone-fused fullerenes. The reactants were generated in situ by the oxidation of the readily available 2-methoxy phenols with hypervalent iodine agents. For the several different masked ortho-benzoquinones that were tested, it was found that the yield of the cycloadducts depends on the nature of the starting materials and the reaction conditions. Other Diels-Alder reactions of such electron-deficient dienes with electron-poor fullerenes involved tropones [94], 1,3-butadienes substituted with electron-withdrawing groups [95], and 2-pyrone [96]. 

As shown in Figure 41, Kobayashi s catalysis was also effective for asymmetric aza Diels-Alder reactions, and in this case 2.4 equiv. of DBU was used instead of 1,3,5-trimethylpiperidine. 2,6-Di-/m-butyl-4-methylpyridine appeared to be most effective additive 95 Mark6 et al. have reported that these catalysts are also effective for asymmetric inverse electron-demand Diels-Alder reactions of 2-pyrone... 

Figure 42. Catalytic, asymmetric Diels-Alder reaction of 2-pyrone derivatives.

Fig. 15. Bicyclo [2.2.2] octene units containing polyimide obtained by Diels-Alder reaction of a BMI with 2-pyrone...

E. Marko, G. R. Evans, P. Seres, I. Chelle, Z. Janousek, Catalytic, enantioselective, inverse electron-demand Diels-Alder reactions of 2-pyrone derivatives, Pure Appl. Chem. 1996, 68, 113. 

The Diels-Alder reaction of 2-pyrones has been used in polymer syntheses (6, 13) (Reaction 4). In these reactions the 2-pyrone is difunctional in that it consumes two moles of dienophile (Reaction 16). A practical way of stopping at the 1 1 adduct is to use an acetylenic monomer (24) (Reaction 17). Although 2-pyrone itself polymerizes on standing (I), phenyl-substituted 2-pyrones, including monophenyl 2-pyrones, are stable at ordinary temperatures. 

A better accessible chiral mediator is the (acyloxy)borane (CAB) 2-64 prepared in situ from a tartaric acid derivative and arylboronic acid at room temperature. Hetero Diels-Alder reaction of benzaldehyde and Danishefsky s diene 2-10 in the presence of 2-64 gave the corresponding pyrone after acidic work up with 52 - 95 % ee depending on R. The best results were obtained with R = 2,4,6-Me3Ph and 2,4,6-iPr3Ph. Similarly, with 2-60 the pyrone 2-61 with up to 97% ee was found [107]. 

Diels-Alder reactions. This pyrone does not react with moderately reactive dienophiles (ethyl acrylate), but does react with reactive symmetrical alkenes to give adducts resulting from addition of 2 equiv. of the dienophile with loss of CO2 from the primary cycloadduct. It also reacts with acetylenic dienophiles to form m-tliincthoxyarencs. 

Diels-Alder reactions of 2-pyrone with various dienophiles are well known to give the corresponding [4 2] cycloadducts in good yields. - Although the reaction of allyl cations with 2-pyrones has not, to... 

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