Reactions of Pyrones

With bromine, 2-pyrone forms an nnstable addnct that gives the substitution product 3-bromo-2-pyrone on warming, however this can also be obtained satisfactorily by bromodecarboxylation of 2-pyrone-3-carboxylic acid coumalic acid (2-pyrone-5-carboxylic acid) gives 5-bromo-2-pyrone or 3,5-dibromo-2-pyrone (See also 11.2.2.3 and 11.4.2 for syntheses of halo-2-pyrones). 

With nitronium tetrafluoroborate, the electrophile is assnmed to attack first at carbonyl oxygen, leading subseqnently to 5-nitro-2-pyrone. Simple examples of electrophilic substitntion of 4-pyrones are rare, however bis-dimethylaminomethylation of the parent heterocycle takes place under quite mild conditions.  

2-Pyrones are in many ways best viewed as unsaturated lactones, and as such they are easily hydrolysed by aqueous alkali 4-pyrones, too, easily undergo ring-opening with base, though for these vinylogous lactones, initial attack is at C-2.  

2-Pyrones can in principle add nucleophilic reactants at either C-2 (carbonyl carbon), C-4 or C-6 their reactions with cyanide anion, and ammonia/amines are examples of the latter, whereas the addition of Grignard nucleophiles occurs at carbonyl carbon. 

4-Pyrones also add Grignard nucleophiles at the carbonyl carbon, C-4 dehydration of the inunediate tertiary alcohol product with mineral acid provides an important route to 4-mono-substituted pyrylium salts. More vigorous conditions lead to the reaction of both 2- and 4-pyrones with two mole equivalents of organometallic reagent and the formation of 2,2-disubstituted-2H- and 4,4-disubstituted-4//-pyrans, respectively. Perhaps surprisingly, hydride (lithium aluminium hydride) addition to 4,6-dimethyl-2-pyrone takes place, in contrast, at C-b.  

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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],... 

The formation of aromatic rings via rDA processes has found application in the synthesis of many natural products only a representative set can be presented here. Pyrenochaetic acid A (134), a phytotoxic metabolite, was synthesized by a process involving a rDA reaction as a key step. The DA reaction of pyrone (132) with ethyl propiolate gave, after isolation, benzoate (133) via a rDA reaction evolving carixin dioxide (equation 60). A synthesis of a-cartopterone (137) has been achieved that involves the rDA elimination of ethylene. The tey step is rDA decomposition of adduct (135) to naphthoquinone... 

The IMDA reaction of pyrone 167, which bears a chiral tether proceeded in a highly diastereoselective fashion to provide 168a-e t/o in 68% yield (95% based on a 72% conversion of 167), upon heating at 110 °C in toluene (Scheme 43) <06AG(E)>. 

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

West reported the reactions of pyrones with furans to generate seven-membered ring products in modest yield (Eq. 50). This is a beautiful example of a reaction that allows for a great increase in complexity in a single transformation. 

Elevated pressure was also necessary to force the reaction of pyrone 47 with substituted vinyl ethers 48E and 48Z. Interestingly, geometric isomer 48Z reacts considerably faster and with better stereoselectivity than 48E. Thus, 48Z cycloadded to give 38% of cycloadducts 49... and 49 in a ratio of 18 1. By contrast, 48E cycloadded to give a very low yield of cycloadducts 50-.,- and in a ratio of 2 1. In each reaction, the olefin stereochemistry was retained in the reaction products, indicating that these cycloadditions occur in a concerted rather than in a stepwise fashion. 

An early report by Thornton and co-workers indicates low levels of diastereocontrol in the reaction of pyrone 61 with ethyl vinyl ether. ... 

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)... 

Scheme 10 Reactions of pyrones 21 with amines in the presence of an acid...

In the absence of a strong acid, compounds 27 can be prepared as a mixture of two tautomers (R =Cp3, 27 27 =21 79 RF=Cp2H, 27 27 =65 35) from the reaction of 6-R -comanic acids 21b,d with o-phenylenediamine. To transform 27 into more conjugated tautomers 27 the mixtures were heated in DMSO at 80-120 °C. Under the same conditions reaction of pyrone 21b with o-aminophenol led to the formation of benzo[fe][l,4]oxazin-2-one28 [17] (Scheme 11). 

The propensity of a-pyrones to undergo the Diels-Alder reaction makes them useful for syntheses of highly substituted aromatics and biphenyls. A practical method for the regioselective synthesis of the A-benzoyl-4-(polyfluoroalkyl)ani-lines 82 by thermal Diels-Alder cycloaddition of 71 with fluorostyrenes and acetylenes was described. Free 4-(polyfluoroalkyl)anilines were smoothly formed in good yields by DBU-assisted deprotection. In the case of the reactions of pyrone 71a with isobutyl vinyl ethers and cyclic vinyl ethers, compounds 83 and 84 were obtained, respectively [36] (Scheme 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. 

C-1,2-addition pathway. The reaction of pyrone 15 led to the pyran product 16 in an improved yield, and gave previously unknown products 37b and 37c (Scheme 12.6). Our protocol allowed preparations of analogs such as 30,38, and 39, with 30 being comparable to the yields of Hua et al. In addition, we were able to constmct oxa-spirocycles such as 40-42, with 41 (the major isomer is shown) and 42 possessing moderate diastereoselectivities [25]. 

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