Diels-Alder reaction, with iminium salts

Aza-Diels-Alder reactions in aqueous soiutions cycioaddition of dienes with simpie iminium salts generated under Mannich conditions [22]... 

The aza-Diels-Alder reaction combines three components (an aldehyde, an amine salt and a diene) to produce heterocyclic products which are useful synthetic intermediates. Grieco first reported that such a reaction could occur in water. Preliminary studies focused on the reaction of dienes with iminium ions generated by an amine hydrochloride and 37% aqueous formaldehyde solution [59]. When dienylamine hydrochlorides are treated with aqueous formaldehyde at 50 °C, bicyclic ring systems are formed (Scheme 9). 

Other reactions are possible with iminium salts derived from a,p-unsaturated carbonyl compounds. The Baylis-Hillman reaction (chapter 18) also uses conjugate addition as a first step and we shall deal with that immediately. Much more work has been done on the Diels-Alder reaction that will follow. The Baylis-Hillman reaction between an electrophilic a,p-unsaturatcd carbonyl compound and an... 

Cycloaddition reactions. Asymmetric induction in cycloaddition of enals is based on the formation of conjugated iminium salts with bulky prolinol derivatives. Reaction partners include enamides and cyclopentadiene. The Diels-Alder reaction (catalyst 3B) is exo-... 

Cycloadditions of iminium compounds with 1,3-dienes to afford Diels-Alder adducts seems to be a reaction of general applicability.46 On the other hand, simple electron-rich imino species are less reliable dienophiles. Some electron-rich imines will undergo Diels-Alder reactions under acid catalysis and thus are probably actually reacting as iminium salts. However, inverse electron demand [4 + 2] cycloadditions of neutral imines with electron-deficient dienes have been reported, as have additions to exceptionally reactive dienes (vide infra). 

Grieco and co-workers also showed that iminium salts such as 123, formed by reaction of an amine and formaldehyde (sec. 4.4) reacted with cyclopentadiene in aqueous media to give a near-quantitative yield of the Diels-Alder adduct. An internal Diels-Alder reaction was also possible (sec. 11.8). Treatment of an aqueous solution of 124 with formaldehyde at 50°C gave a 98% yield of indolizidine 125. 

In Diels-Alder reactions a,P-unsaturated oxazolines react with various dienes (1, 2, 12, 14) stereoselectively via the acyl iminium salts derived by A-acylation with trifluoroacetic anhydride. 

From the numerous ir-systems investigated, nitrogen-containing dienophiles are the most typical carbonyl derivatives for hetero Diels-Alder reactions. Simple imines, however, are quite unreactive and require highly reactive dienes as counterparts. - In contrast, electron-deficient species, such as iminium salts (134 Scheme 63) or N-acylimines (137 Scheme 64), do undergo [4 -t- 2] cycloadditions with normal nonactivated dienes. Thus, the intramolecular Diels-Alder reaction of the iminium species (134), created in situ from the aldehyde (133) and ammonia, gives the octahydroquinoline (135), which can be hydrogenated to afford the 8a-epimer of pumiliotoxin C (Scheme 63). ... 

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