2-pyrone cycloaddition

SCHEME 16.36 Synthesis of highly substituted anilines from 2-pyrone cycloaddition. 

SCHEME 16.37 2-Pyrone cycloaddition to silicon-bridged cyclophane. 

Finally, in a very recent disclosure, Lee et al. (165) approached the total synthesis of arteminolide using a [5 + 2] cycloaddition strategy with an oxidopyrylium ion. Despite its long history of use, Lee was the first to utilize an allene moiety both in an intra- and an intermolecular cycloaddition with oxidopyrylium ions. By utilizing a pyrone cycloaddition precursor (294) similar to those used in the Wender phorbol synthesis, Lee was able to synthesize various ring sizes and... 

We thank the NSF and the NIH for support of our research at Johns Hopkins University on fundamental aspects and synthetic applications of pyrone cycloadditions. 

A strategy for the synthesis of highly substituted anilines and o-phenylenediamine derivatives has been developed based on pyrone cycloaddition with acetylenic dienophiles (Scheme 16.36) [39]. 

A synthesis of 2-alkyl-2,3-dihydro-y-pyrones (187) from methoxybutenyne and aldehydes has been described (83TL4551). The condensation of lithiomethoxy-butenyne (184) with aldehydes at -78°C leads to the secondary alcohols 185, which form the dihydropyrones 187 via hydration of the acetylenic bond and hydrolysis of the methoxyethenyl group to the ketoenol 186 (0°C, p-TSA, THF, H2O or 30% HCIO4, 20 min) folowed by intramolecular cycloaddition. 

The TMM [4-1-3] cycloaddition to pyrone has been employed in a synthetic study of a novel biologically active diterpene pseudolaric acid B (106), in which the formation of the bridged adduct (107) from the 2-pyrone (108) is the key step in the sequence (Scheme 2.29). A mixture of the other isomer (109) and the methylenecyclopentane (110) was also isolated from the reaction. It is important to point out that the presence of a tin co-catalyst is critical in effecting the reaction. This is the first example a "tin-effect observed in a [4-1-3] cycloaddition [40]. 

A novel use of a chlorofluorocarbon is in the synthesis of a pyrone (30) from 1,1,1-trichlorotrifluoroethane. The key step involves Cu(I) catalysis. Pyrone (30) is a useful CF3 aromatic synthon, as it readily underwent (4 + 2) cycloaddition followed by spontaneous elimination of C02 (85-TL3947). 

Racemic pyrone sulfoxide 52 undergoes a diastereoselective inverse-electron-demand 2 + 4-cycloaddition with 1,1-dimethoxyethylene to afford adduct 53 in > 95% yield (equation 49)100 this is the first example of an asymmetric Diels-Alder cycloaddition using a sulfinyldiene as an electron-deficient enophile101. 

The 2-pyrones can behave as dienes or dienophiles depending on the nature of their reaction partners. 3-Carbomethoxy-2-pyrone (84) underwent inverse Diels-Alder reaction with several vinylethers under lanthanide shift reagent-catalysis [84] (Equation 3.28). The use of strong traditional Lewis acids was precluded because of the sensitivity of the cycloadducts toward decarboxylation. It is noteworthy that whereas Yb(OTf)j does not catalyze the cycloaddition of 84 with enolethers, the addition of (R)-BINOL generates a new active ytterbium catalyst which promotes the reactions with a moderate to good level of enantio selection [85]. 

Commercial chromatography silica gel promotes effectual Diels-Alder cycloaddition of optically active pyrone lactate ester (5) with benzyl vinyl ether (6), affording the endo adduct 7 in an approximately 4 1 mixture of diastereoisomers [16] (Equation 4.1). 

Whereas electronically activated 2-pyrones can react thermally in both normal and inverse electron-demand Diels-Alder cycloaddition, 2-pyrone by itself requires thermal conditions that are so vigorous that they cause spontaneous extrusion of carbon dioxide from the bicyclic cycloadduct [61]. 

Posner G. H., Bull D. S. Recent Advances in Control of Absolute Stereochemistry in Diels-Alder Cycloadditions of 2-Pyrones Recent Res. Dev. Org. Chem. 1997 1 259-271... 

Posner G. H. Stereocontrolled Synthesis of Functionalized Cyclohexenes Via Diels-Alder Cycloadditions of 2-Pyrones and 2-Pyridones-Applications to Synthesis of Physiologically Active Compounds in Stereocontrolled Org. Synth. 1994 177, Ed. Trost B. M., Pb. Blackwell Oxford... 

Scheme 15. Thermal cycloaddition of a-pyrone to sila[3]pericycline 74...

The [2-I-2-I-2] cycloaddition reaction of diynes 40 and carbon dioxide 41 were successfully catalysed by a NHC-nickel (Scheme 5.12) [15]. The NHC-Ni complex was prepared in situ from [NiCCOD) ] and two equivalents of carbene. Pyrones 42 were obtained in excellent yields at atmospheric pressure of CO and mild reaction conditions. 

When benzyne is generated in the absence of another reactive molecule it dimerizes to biphenylene.132 In the presence of dienes, benzyne is a very reactive dienophile and [4+2] cycloaddition products are formed. The adducts with furans can be converted to polycyclic aromatic compounds by elimination of water. Similarly, cyclopentadienones can give a new aromatic ring by loss of carbon monoxide. Pyrones give adducts that can aromatize by loss of C02, as illustrated by Entry 7 in Scheme 11.9. 

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