Diels diene carboxylate salts

Since Breslow s report, aqueous Diels-Alder reactions have gained much attention and a range of substrates have been studied, including the use of hydrophilic acid [98] or glycol moieties [99] to enhance the diene or dienophile water solubility. Some of the best results were obtained in the reactions of diene carboxylate salts with various dienophiles in water, with micellar effects possibly playing a role in the rate acceleration [100]. 

Sensitive dienol ether functionality in the diene carboxylate was shown to be compatible with the conditions of the aqueous Diels-Alder reaction (Eq. 12.26).84 The dienes in the Diels-Alder reactions can also bear other water-solubilizing groups such as the sodium salt of phosphoric acid and dienyl ammonium chloride (Eq. 12.27).85 The hydrophilic acid functionality can also be located at the dienophile.86... 

In addition, Grieco has contributed extensively to the studies of aqueous Diels-Alder reaction toward the syntheses of a variety of complex natural products. When the EHels-Alder reaction in Scheme 1 was carried out in water, a higher reaction rate and reversal of the selectivity were observed, compared to the same reaction in a hydrocarbcm solvent (6). It should be noted that, for the aqueous reaction, the sodium salt of the diene was used. Water soluble co-solvents caused a rapid reduction in rate. The best result was obtained when the reaction was conducted with a five-fold excess of the sodium salt of diene carboxylate. 

Water-soluble dienes are also used in Diels-Alder reactions in water and they too work very well. Sodium salts of carboxylic acids and protonated amines both behave well under these conditions. Presumably, the soluble tail is in the water but the diene itself is inside the oily drops with the dienophile. In this example an aminodiene reacts with a quinone dienophile. 

Due to the attractivity of this method several groups have developed onium salt supported versions of classical reactions. For example, starting from hydroxyl derived imidazolium salts, formation of supported acrylates with acryloyl chloride followed by reaction with diene in refluxing toluene afforded Diels Alder adduct in good yields (>65%). After saponification, products are isolated without further purification [127], Alternatively, starting from carboxylic acid derived imidazolium salts, acyl chloride formation with thionyl chloride in acetonitrile, followed by reaction with 4-aminophenol led to supported N-arylamide. Williamson alkylation using NaOH as a base and subsequent cleavage from the onium salt support under acidic condition (HCI/I I2()/ AcOH) allowed for isolation of various alkoxy substituted anilines with >98% purity... 

Williams and co-workers have reported a remarkable reversal of regio-selectivity in the intramolecular Diels-Alder reaction of bis-diene substrate 6.25 in connection with efforts toward the total synthesis of ilicicolin (6.23) [77]. They found that heating a toluene solution of 6.25 (R = Et) at 165°C in a sealed tube resulted in the production of regioisomeric cycloadducts 6.26 and 6.27 in the ratio of 3/1 (Scheme 1.12). However, when this Diels-Alder reaction was conducted in boiling water, the product ratio was reversed in favor of 6.27, the highest selectivity (6.27/6.26 = 8/1) being observed when the free carboxylic acid (R = H) or its sodium salt (R - Na) were used. The formation of both cycloadducts is consistent with exo-bridged Diels-Alder transi-... 

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