Dienophiles carbonyl-containing

Furans, thiophenes and pyrroles have all been obtained by addition of alkynic dienophiles to a variety of other five-membered heterocycles, as illustrated in Scheme 104. As the alkynic moiety provides carbons 3 and 4 of the resulting heterocycle, this synthetic approach provides an attractive way of introducing carbonyl containing substituents at these positions, especially as many of the heterocyclic substrates are readily generated. Such reactions do... 

Several aluminum- and titanium-based compounds have been supported on silica and alumina [53]. Although silica and alumina themselves catalyze cycloaddition reactions, their catalytic activity is greatly increased when they complex a Lewis acid. Some of these catalysts are among the most active described to date for heterogeneous catalysis of the Diels-Alder reactions of carbonyl-containing dienophiles. The Si02-Et2AlCl catalyst is the most efficient and can be... 

The synthetic utility of the D-A reaction can be expanded by the use of dienophiles that contain masked functionality and are the synthetic equivalents of unreactive or inaccessible compounds. (See Section 13.1.2 for a more complete discussion of the concept of synthetic equivalents.) For example, a-chloroacrylonitrile shows satisfactory reactivity as a dienophile. The a-chloronitrile functionality in the adduct can be hydrolyzed to a carbonyl group. Thus, a-chloroacrylonitrile can function as the equivalent of ketene, CH2=C=0,63 which is not a suitable dienophile because it has a tendency to react with dienes by [2 + 2] cycloaddition, rather than the desired [4 + 2] fashion. 

A carbonyl group is an effective electron-withdrawing group because the carbonyl carbon bears a partial positive charge (8 ), which withdraws electron density from the carbon-carbon double bond of the dienophile. Common dienophiles that contain a carbonyl group are shown in Figure 16.9. 

The Diels-Alder reaction is one of the most useful synthetic means of preparing cyclic compounds. Although many Diels-Alder reactions have been conducted at high reaction temperatures without catalysts, heat-sensitive compounds cannot be employed in complex multistep syntheses. The Diels-Alder reaction is, furthermore, reversible, and the lowest possible temperatures are generally used. Although Lewis acid catalysts enable the reactions to proceed at room temperature, or below, with satisfactory yields, they are often accompanied by diene polymerization and excess amounts of the catalyst are often needed for catalysis of reactions involving carbonyl-containing dienophiles [20]. 

Lanthanide triflates were also found to be efficient catalysts in the Diels-Alder reactions of carbonyl-containing dienophiles with cyclopentadiene [30]. A catalytic amount of Yb(OTf)3 was enough to promote the reactions to give the corresponding adducts in high yields, and the catalyst could be easily recovered and reused. 

The Diels-Alder reaction occurs primarily in an endo rather than an exo fashion when the reaction is kinetically controlled. A dienophile often contains an electron-withdrawing group, such as a carbonyl or other electronegative group with TT electrons, as in the example below and in all of the examples we have shown thus far. 

Cativiela, C., Garcia, J. I., Mayoral, J. A., and Salvatella, L. Solvent Effects on endo/exo- and Regio-Selectivities of Diels-Alder Reactions of Carbonyl-Containing Dienophiles." /. Chem. Soc., Perkin Trans., 2, 847 (1994). 

Compounds containing a double or triple bond, usually activated by additional unsaturation (carbonyl, cyano, nitro, phenyl, etc.) In the ap position, add to the I 4-positions of a conjugated (buta-1 3-diene) system with the formation of a ax-membered ring. The ethylenic or acetylenic compound is known as the dieTwphile and the second reactant as the diene the product is the adduct. The addition is generally termed the Diels-Alder reaction or the diene synthesis. The product in the case of an ethylenic dienophile is a cyctohexene and in that of an acetylenic dienophile is a cyctohexa-1 4-diene. The active unsaturated portion of the dienophile, or that of the diene, or those in both, may be involved in rings the adduct is then polycyclic. 

Lewis acid catalysis enormously enriches the scope of Diels-Alder reactions, but it is limited to reagents containing Lewis basic sites, i.e. functional groups with lone pairs such as carbonyl, amino, ether or nitro close to the reaction centre. As we have seen in the discussion about the FMO aspects of Lewis acids, the major reason for catalysis is the reduction of the HOMO-LUMO gap. In case of Diels-Alder reactions with normal electron demand, it follows that the coordination of the Lewis acid lowers the LUMO energy of the dienophile. Such interactions are only possible if there is a spatial proximity or an electronic conjugation between the coordinated Lewis basic site and the reaction centre. Fortunately, in nearly every Diels-Alder reaction one of the reagents, mostly the dienophile, meets this requirement. 

Largely because of the widespread interest in cycloadditions, a number of syntheses of dihydropyrans have been developed involving the interaction of four and two atom fragments. Both variations on the [4 + 2] cycloaddition are successful either the diene or the dienophile may be the source of the heteroatom (Scheme 43). A review of heterodiene syntheses with unsaturated carbonyl compounds contains comprehensive lists of dihydropyrans (75CRV651). 

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