Aza Diels-Alder reaction in aqueous media

Retro aza Diels-Alder reactions in aqueous media... 

The study of the aza-Diels-Alder reaction in aqueous media has been restricted in the past to the use of water-soluble dienes and iminium salts. AgOTf has been used to catalyze the reaction of Danishefsky s diene, a water-sensitive reagent, with various imines in aqueous media in good 3deld (eq 13). This process has been extended to the use of three-corrqionent systems that generate the imine in situ (eq 14). 

Bronsted acid catalyzed aza-Diels-Alder reaction of Danishefsky s diene with aidimine generated in situ from aldehyde and amine in aqueous media [107]... 

As in the case of Diels-Alder reactions, aqueous aza-Diels-Alder reactions are also catalyzed by various Lewis acids such as lanthanide triflates.113 Lanthanide triflate-catalyzed imino Diels-Alder reactions of imines with dienes or alkenes were developed. Three-component aza-Diels-Alder reactions, starting from aldehyde, aniline, and Danishefsky s diene, took place smoothly under the influence of HBL4 in aqueous media to afford dihydro-4-pyridone derivatives in high yields (Eq. 12.46).114... 

A novel Mannich reaction between A -alkoxycarbonylpyrroles 739, formaldehyde, and primary amine hydrochlorides catalyzed by Y(OTf)3 gave a monoaminoalkylation product 741 some times in good yield (14-81%) in aqueous media (Scheme 146) <2001TL461>. When formaldehyde was replaced by acetaldehyde or benzaldehyde, no reaction occurred. There was no formation of the 2,7-diazabicyclo[2.2.1]hept-5-ene 740 (through the aza-Diels-Alder reaction of an N-protected pyrrole with an aldehyde and amine salts by catalysis with triflate). 

Another example of the use of Lewis acids in organic reactions in water is the lan-thanide(III) triflate catalysed aza-Diels-Alder reaction, exemplified in Scheme 14. In this reaction the hetero-dienophile is formed in situ from a primary ammonium hydrochloride and a carbonyl compound followed by the actual Diels-Alder reaction . This type of reaction proceeds readily in aqueous media- 296 dramatic increase in... 

The intramolecular aza-Diels-Alder reaction also occurs in aqueous media. This reaction gave fused ring system (Scheme 11). 

---