Furan as a diene

Let US now employ our approach of necessary FMO energy changes for transformation of reactants into corresponding transition state structures. Transition state structures, using the example of furan as a diene, are presented in Figure 2. It is interesting to note that... 

The reaction barrier firmly supported our previous finding that 1,3,4-oxadiazole should react with highly reactive dienophiles. In fact, it was predicted that the reaction between 1,3,4-oxadiazole and cyclopropene should be possible under moderate reaction conditions (room temperature). For reactions with dienophiles of low reactivity such as ethylene, forceful reaction conditions or even activation of the diene or dienophile are required. Both 1,3,4-triazole and 1,3,4-thiadiazole were predicted to have activation barriers that were 6 kcal/mol and correspond to comparable reactivities. In all cycloaddition reactions with cyclopropene as a dienophile, an exo cycloadduct is predicted to be a major or exclusive product, which is in agreement with some of our previous studies of cycloaddition reactions with furan as a diene and cyclopropene as a dienophile. 

Keay - High pressure intramolecular Diels-Alder reaction of furan as a diene I89TL1045]... 

The balance between aromatic and aUphatic reactivity is affected by the type of substituents on the ring. Furan functions as a diene in the Diels-Alder reaction. With maleic anhydride, furan readily forms 7-oxabicyclo [2.2.1]hept-5-ene-2,3-dicarboxyhc anhydride in excellent yield [5426-09-5] (4). 

Intramolecular Diels-Alder reactions employing furan as the diene component are an effective step in the synthesis of many natural products, but difficulties are sometimes encountered due to the poor dienic character of the aromatic ring. Using CDs can help to overcome this problem. Thus, when 73 is heated in water at 89 °C for only 6h a 20% epimeric 1 2 mixture of 74 and 75 is... 

Entry 15 creates a portion of the steroid skeleton and also illustrates the use of a furan ring as a diene. 

As a result of its reduced aromaticity, relative to pyrrole, furan undergoes [4 + 2] cycloaddition reactions much more readily. It combines as a diene with electron-poor dienophiles to yield Diels-Alder-type adducts. Maleic [(Z)-butenedioic acid] anhydride, for example, reacts at room temperature, and the only isolated adduct is the exo isomer (the more thermodynamically favoured adduct) (Scheme 6.27a). 

Furan can act as a diene in cydoaddilion reactions, but pyrrole only does so when activated by A-substilulion with an electron-withdrawing group. Thiophene I, I-dioxide is also an effective diene component in [4 + 2] cycloadditioiis. 

Furan is the least aromatic of the five-membered ring heterocyclics and acts as a diene toward strong dienophiles. 

In the fused compounds (241) and (242) the furan ring fails to react as a diene and Diels-Alder reaction with dienophiles occurs on the terminal carbocyclic rings. However, (243) and (244) afford monoadducts with dimethyl fumarate by addition to the furan rings (70JA972). The rates of reaction (Table 2) of a number of dehydroannuleno[c]furans with maleic anhydride, which yield fully conjugated dehydroannulenes of the exo type (247), have been correlated with the aromaticity or antiaromaticity of the products (76JA6052). It was assumed that the transition state for the reactions resembled products to some extent, and the relative rates therefore are a measure of the resonance energy of the products. The reaction of the open-chain compound (250), which yields the adduct (251), was taken as a model. Hence the dehydro[4 + 2]annulenes from (246) and (249) are stabilized compared to (251), and the dehydro[4 ]annulenes from (245) and (248) are destabilized (Scheme 84). 

Furan has much greater reactivity in cycloaddition reactions compared to pyrrole and thiophene the latter is the least reactive as a diene. N-Substituted pyrroles often show enhanced diene character compared with the parent heterocycle, especially when the N-substituent is electron withdrawing. 

Furan reacts as a diene with powerful dienophiles such as maleic anhydride, maleimide, and benzyne to give Diels Alder adducts. The kinetically favored products are the undo adducts but the exo adducts are thermodynamically preferred (Scheme 95). Thus, on prolonged reaction at room temperature, or on heating, the proportion of exo to endo adduct is increased. 

The copolymerization of furan and 2-methylfuran with dienophiles such as maleic anhydride leads to polymer structures with furan pendent functionality. Furan, 2-methylfuran, and 2,5-dimethylfuran have been copolymerized with acrylic monomers (51,52) and acrylonitrile (52,53). The furan ring of furan, 2-methylfuran, and 2,5-dimethylfuran participates as a diene in a free radical copolymerization with acrylonitrile. The initial step for furan and for 2,5-dimethylfuran is the attachment of an acrylonitrile radical at the 2-position, but for 2-methylfuran, the attack is at the-5-position. Propagation proceeds by the attack of the furan radical on an acrylonitrile molecule, to leave one olefinic bond in the structure derived from the furan ring. If this bond is in the 4,5- or 2,3-position, it may be involved in a second additional reaction by the return of the propagating chain. 

The copper catalyzed Diels-Alder reactions of a variety of dienes have been elegantly exploited by Evans as a key step in the synthesis of natural products (Sch. 49). The synthesis of tetrahydrocannabinol (219) [92] employs the acyclic diene 217 furan is used as a diene in the synthesis of shikimic acid (222) [93]. Although the methodology uses the very reactive catalyst 188, the reactions are still slow, suggesting that less reactive dienes require longer reaction times and higher temperatures for completion. A copper Lewis acid-mediated intramolecular Diels-Alder reaction has served as a key step in the total synthesis of isopulo upone [94]. 

There are just a few one-pot reactions in which two carbon-carbon bonds are simultaneously formed. One of these is the ancient but exceedingly useful Diels-Alder reaction, for which furans are particularly popular dienes. Consequently there would be nothing unusual about having compound I and methyl vinyl ketone (MVK) coupled in a Diels-Alder cycloaddition mode except for the fact that 2,5-disubstituted furans are known to be reluctant dienophiles. However, the amino group at C-2 considerably increases the reactivity of the furan nucleus as a diene by injecting electron density into the ring s x system. This phenomenon is underscored by the regiospecificity of the cycloadditon. 

It has been further demonstrated that furan may be successfully employed as a diene using catalyst 10 and a-halo acroleins as the 27t component (Scheme 13)... 

These are the only examples to date of a furan reacting as a diene with a cyano dienophile. Taylor and French have recently reported two intramolecular cyclizations of nitrile dienophiles with triazines to give fused heterocycles [Eq. (8)] in modest yields.12b... 

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