Pyrone derivatives

Baiker s group employed the 4-methoxypyrone as a standard substrate thereafter. Under noncatalyhc conditions (the use of a stoichiometric amount of CN), a 94% ee and 95% de at an 80% conversion were achieved [118], A stereochemical model of CN adsorption onto the palladium surface, and interaction of the pyrone derivatives with CN, were also proposed on the basis of spectroscopic investigations, product analysis and computational studies [119]. 

In addihon to hydrogenation of the a,P-unsaturated acid and 2-pyrone derivahves, unsaturated esters were also demonstrated for the hydrogenahon over the CD-modified palladium catalyst. However, at present, the product ee-value is not sufficienhy high [120-122]. 

The author thanks Emeritus Professors Akira Tai, Yuriko Nitta and Tadashi Okuyama, who provided much help when they were his coworkers. He also thanks all his former and present students. 

After the submission of the draft on June, 2007, many progress has been made in this field. Many of them will be reviewed somewhere else, but here, one good review is added. Mallat, T., Orglmeister, E., Baiker, A. (2007) Chemical Review, 107, 4863-4890. 

1 For results before 2000, see (a) De Vos, D.E., Vankelecom, I.F.J. and Jacobs, P.A. (eds) (2000) Chiral Catalyst Immobilization and Req/cling, Wiley-VCH Verlag GmbH, Weinheim. 

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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... 

Schulte and coworkers (62AP801) have prepared a number of 3-propargyl-4-hydroxy-2-pyrone derivatives (210) by condensation of /3-dicarbonyl compounds (208) with propargyl-malonyl chloride (209). On heating (210) with zinc carbonate, ring closure took place to give the corresponding furo[3,2-c]pyrone derivatives (211 Scheme 40). 

BSB451). Metalated enamines (in the a-methyl group) easily react with aldehydes, and the new enamines thus formed undergo an intramolecular cyclization giving 2-pyrone derivatives (84T733) (Scheme 41). 

A different route to pyrones is the preparative electrochemical oxidation of enamines in acetonitrile in the presence of tetraethylammonium perchlorate (88MI2) (Scheme 46). The synthesis of 2-pyrone derivatives has been carried out by reaction of /3-dicarbonyl compounds with methyl-a-benzoylamino-/3-dimethylaminoacrylate (96JHC751). Thiapyran derivatives can be obtained by interaction of enamines based on (/3-amino-a-cyanoacryloylmethyl)pyridinium chloride derivatives with carbon disulfide (95M711).The synthesis of pyridine derivatives based on analogous enamines has been described as well (95M711). 

The photorearrangement of certain epoxycyclopentenones takes a different course to yield 2-pyrone derivatives one example is the conversion of 3,4-diphenyl-4,5-epoxycyclopent-2-en-l-one (20) into 4,5-diphenyl-2-pyrone (21), and this can be rationalized by assuming cleavage of the oxirane to give the diradical (22) or its equivalent,... 

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

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. 

Hydrogenolysis of 2-pyrone derivatives to give open-chain products occurs especially readily when phenyl group is substituted in the 6 position.237,238 4-Ethoxy- and 4-hy-droxy-6-phenyl-5,6-dihydro-2-pyrones were hydrogenated to give 3-ethoxy-5-phenyl-2-pentenoic acid and 3-hydroxy-5-phenylvaleric acid, respectively, over Raney Ni at room temperature and 0.3 MPa H2 (eq. 12.126).237... 

Pyrone derivatives, synthesis of using ketene dithioacetals 89-YGK413. 

The examples given in Scheme 2.121 are typical of the general approach used to prepare six-membered rings bearing functional groups at any position via the Diels-Alder route from a diversified set of dienes and dienophiles. The flexibility of this protocol is further illustrated in Scheme 2.122. Utilization of 2-pyrone derivatives as diene components opens an entry toward the preparation of 1,3-cyclohexadienes via Diels-Alder reactions followed by a ready elimination of carbon dioxide from the initally formed adduct. For example, reaction of 338... 

Another characteristic general photochemical reaction of a,j3-epoxyketones is the transformation of disubstituted cyclopentenone oxides to 2-pyrone derivatives (Eq. 

Irradiation of 3,5-dimethyl-4-pyrone in trifluoroethanol leads to cyclopentenone-oxirane, which on further irradiation is converted to a 2-pyrone derivative and a l3-diketone. A photoadduct is also formed with the solvent (Eq. 347). ... 

Pyrone derivatives containing a 2-pyridyl substituent at C3 can undergo Lewis-acid catalyzed DA cycloadditions with electron-rich dienophiles. Shown in Scheme 30 is the ZnBrj catalyzed cycloaddition of 100 with BVE. After 48 hours at -20 °C, the reaction afforded endo-cycloadduct 102 as only product in 81% yield. 

Inverse electron-demand asymmetric Diels-Alder reactions of 2-pyrone derivatives were reported (a) Posner GH, Carry J-C, Lee JK, Bull DS, Dai H (1994) Tetrahedron Lett 35 1321 (b) Markd IE, Evans GR (1994) Tetrahedron Lett 35 2771... 

As shown in Fig. 12.1, a 6300-fold increase in potency is observed when the hydroxylic hydrogen is replaced by a diethyl-methyl side chain. A comparable increase in potency is observed in a series of 1-methyl-1,2,3,4-tetrahydro-pyridyl-pyrazines described by Ward et al. exhibiting Mj muscarinic agonists. In changing from O-methyl to O-butyl, the aflSnity for the Mj receptor varies from 850 nM to 17 nM. Another example is found in a series of 2-pyrone-derived elastase inhibitors. ... 

The catalytic reaction of complex 49 with dtbcH2 and dioxygen is less selective than that of 50. In addition to the formation of dtbq and 3,5-di-ter -butyl-l-oxa-cyclohepta-3,5-diene-2,7-dione, some muconic acid anhydride and 2-pyrone derivatives are also produced as a result of both intra- and extradiol insertion of one of the oxygen atoms from dioxygen. Such products are consistent with the mechanism in Scheme 10, with the proviso that both the rhodium and iridium systems share the same mechanism, at least in the initial stages of the reaction. 

In [4+2] cycloaddition reactions of chiral 2-pyrones derived from chiral auxiliary 19 high endolexo selectivities and diastereoselectivities were obtained with vinylethers in the presence of a catalytic amount of Pr(hfc)3 or Eu(hfc)3. 

Lesage, S., and A. S. Perlin Synthesis and Stereochemistry of 2-Pyrone Derivatives Related to Some Fungal Metabolites. Can. J. Chem. 56, 2889 (1978). 

Pyrone derivatives 134—136 were synthesized in facile one-step fashion from easily accessible and stable 126 and readily accessible... 

A number of 2-pyrone derivatives with aromatic substituents are widely distributed in several plant taxa, such as Lauraceae, Annonaceae, Leguminosae, or Piperaceae. Compounds of chemotaxonomic importance are described in the literature (47) and elsewhere in this book. In contrast, aliphatic <5-lactones are rather uncommon in plants and only a limited number of them have been isolated from woody plants. 

Thus, we have developed catalytic asymmetric aza Diels-Alder reactions of imines with alkenes using a chiral lanthanide Lewis acid, to afford 8-hydroxyquinoline derivatives in high yields with high diastereo- and enan-tioselectivities. The characteristic points of this reaction are as follows, (i) Asymmetric aza Diels-Alder reactions between achiral azadienes and dienophiles have been achieved using a catalytic amount of a chiral source, (ii) The unique reaction pathway, in which the chiral Lewis acid activates not dienophiles but dienes, is revealed. In most asymmetric Diels-Alder reactions reported using chiral Lewis acids, the Lewis acids activate dienophiles [64, 65]. However, inverse electron-demand asymmetric Diels-Alder reactions of 2-pyrone derivatives have been reported [72]. (iii) A unique lanthanide complex including an azadiene and an additive, which is quite different from the conventional chiral Lewis acids, has been developed. 

Methyl propiolate and triethylamine added to refluxing 3 -hydroxy-4, 5 -di-methoxy-l,2-benzo-l-cyclohepten-4-one in abs. benzene-terf-pentanol, refluxed 45 min., K-fert-butoxide soln. added, and refluxing continued for 30 min. -> hydroxydimethoxy-2-pyrone derivative. Y over 70%. Also isolation of intermediates s. J. Schreiber et al., Helv. 44, 540 (1961). 

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