Dienophiles, alkynes acids

Furan also undergoes cycloadditions with allenes and even with simpler dienophiles, like acrylonitrile and acrylate (specifically enhanced by the presence of zinc iodide),and with maleate and fumarate esters, if the addition is conducted under high pressure. This device can also be used to increase markedly the reactivity of 2-methoxy- and 2-acetoxyfuran towards dienophiles. Lewis acid catalysis can also been used to accelerate furan Diels-Alder additions. At higher reaction temperatures alkynes and even electron-rich alkenes will add to furan. 

Esters of a-diazoalkylphosphonic acids (95) show considerable thermal stability but react with acids, dienophiles, and triphenylphosphine to give the expected products. With olefinic compounds in the presence of copper they give cyclopropane derivatives (96), but with no such compounds present vinylphosphonic esters are formed by 1,2-hydrogen shift, or, when this route is not available, products such as (97) or (98) are formed, resulting from insertion of a carbenoid intermediate into C—C or C—H bonds. The related phosphonyl (and phosphoryl) azides (99) add to electron-rich alkynes to give 1,2,3-triazoles, from which the phosphoryl group is readily removed by hydrolysis. 

Triazines react also with electron-rich dienophiles such as ethyl vinyl ether (401 R = Et) or vinyl acetate (401 R = Ac) in boiling dioxane to yield the pyridine derivatives (376). After the usual [4 + 2] cycloaddition and nitrogen elimination from the bicyclic compound (402), the dihydropyridines (403) eliminate ethanol or acetic acid to give the aromatic pyridines (376). The dienophiles (401) can therefore be used as alkyne equivalents (69TL5171). 

Pyrrole has also been utilized to some extent as a diene in Diels-Alder reactions to give functionalized 7-azabicylo[2.2.1]heptenes and 7-azabi-cyclo[2.2.1]heptadienes.4 While the synthetic utility of this reaction is limited by the aromatic stability of the pyrrole ring, the use of Lewis acids, electron-withdrawing groups on the pyrrole, alkyne dienophiles, and high pressures have allowed pyrroles to be employed in the synthesis of several azanorbomane targets.4... 

Alkene- and alkyne-substituted Fischer carbenes participate as dienophiles in Diels-Alder reactions. The conditions are usually mild and the reaction proceeds smoothly at room temperature. Similar isomeric ratio and rate acceleration is observed to that of Lewis acid-promoted Diels-Alder reactions between methyl acrylates and dienes when compared to the uncatalyzed reactions. The reactions are endo-selective. Asymmetric Diels-Alder reactions are... 

The classical version of the Diels-Alder reaction uses a 1,3-diene as the 4it component and an alkene or alkyne containing electron-withdrawing groups (conjugated aldehydes, ketones, acids and their derivatives, nitroalkenes, etc.) as the 2n reactant. With appropriately chosen dienes and/or dienophiles, a wide array of purely carbocyclic or heterocyclic compounds can be easily synthesized. A representative set of simple examples is given in Scheme 2.118. 

Diels-Alder Reactions. Chiral a,p-unsaturated imides participate in Lewis acid-promoted Diels-Alder cycloaddition reactions to afford products in uniformly excellent endo/exo and endo diastereoselectivities (eq 50 and 51). Unfortunately, this reaction does not extend to certain dienophiles, including methacryloyl imides, p,3-dimethylacryloyl imides, or alkynic imides. Cycloadditions also occur with less reactive acyclic dienes with high diastereoselectivity (eq 52). Of the auxiliaries surveyed, the phenylalanine-derived oxazolidinones provided the highest diastereoselectivities. This methodology has been recently extended to complex intramolecular processes (eq 53). In this case, use of the unsubstituted achiral oxazolidinone favored the undesired diastereomer. 

Thus, the reaction of 144 with alkynes yielded polymer-bound intermediates 145. The release of the final products was performed in two steps. After cleavage of the Boc group under acidic conditions, the products 146 were cleaved from the support under basic conditions. In addition to alkynes, other dienophiles such as enol ethers could also be employed. 

Danishefsky has exploited his widely utilized silyloxydiene chemistry to complete a formal total synthesis of 90 (Scheme 1.20). By employing the appropriate oxidation levels for both the diene and dienophile, a resorcinyl ester possessing the required differentiation of the phenolic groups was obtained without further oxidative manipulation. To this end, the dianion of propiolic acid was alkylated with l-bromo-7-octene to give acid 98 in 68% yield. Further alkylation with methyl iodide then gave the ester 99. A Diels-Alder reaction with diene 100, a derivative of methyl acetoacetate, and alkyne 99 then furnished an initial phenolic intermediate which was protected as the benzyl ether to afford... 

After the [4 + 2] cycloaddition and nitrogen elimination from the bicyclic intermediate, the dihydropyridines 19 eliminate alcohol, thiol, amine or acetic acid to afford the aromatic pyridines 20. Thus the dienophiles function as alkyne equivalents.386... 

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