Pyrone-ring construction

Most reports concerning 2//-pyran-2-ones (a-pyrones) involve non-fluorinated derivatives, which perform important biological functions in nature and have unlimited synthetic potential for the construction of a variety of arenes and heteroarenes [28], However, very few deal with 2-pyrones containing fluoroalkyl groups. It is evident that the C-2, C-4 and C-6 positions of the 2-pyranone ring are electrophilic in nature and prone to nucleophilic attack. The presence of polyfluoroalkyl substituents on the pyrone ring favours these reactions. At the same time, R -containing 2-pyrones behave as cyclic dienes in cycloadditions. 

Only a limited number of metal-mediated approaches for the construction of the pyrone ring of coumestans have been reported to date in the literature. In this context, Larock and coworkers developed an efficient synthesis of coumestrol in which the pyrone ring is formed through a palladium-catalyzed carbonylation/lactonization of the 2-aryl-3-iodobenzofuran derivative 93, accessible by iodocyclization of the fxmctionalized diphenylacetylene 92 (Scheme 41) [140]. 

Recently, pyrone [2 + 2]-photocycloaddition reactions were used to construct macrocyclic compounds. A dipyrone was irradiated in the presences of a,(0-diolefins yielding 18- to 25-membered rings by a sequential intermolecular and intramolecular cycloaddition [146]. 

The reaction of thioenol aryl ethers with 1,3-diketones mediated by Ag2C03 on Celite leads to a facile construction of medium- and large-sized ring-substituted furans (Equation 36) <20000L1387>. This method has been exploited in syntheses of dibenzofurans, coumestans, and 4-pyrones. 

The second approach constructs the C-ring, and uses a benzyne-pyrone cycloaddi-tion. Yields were good, usually in the 70-80% range (6 examples). The nitrogen in 705... 

The classical general method for constructing 2-pyrones is that based on the cyclising condensation of a l,3-keto(aldehydo)-acid with a second component which provides the other two ring carbons. 

The [4+3] cycloaddition reaction offers a convenient way to prepare relatively complex seven-membered rings from simple starting materials. Using MBH adducts 352 as C3 component, a phosphine-catalyzed [4 + 3] annulation has been developed to construct the bicyclo[3.2.2]nonadiene skeleton (Scheme 4.112). The reactions proceeds smoothly with various MBH adducts as well as various substituted pyrones 353 such as ester, nitrile and amide substituted pyrones, resulting in compounds 354 in moderate to good yields. 

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)... 

---