Azadienes imino Diels-Alder reaction

Catalysts such as Fe(BuEtCHC02)3 have been d eloped that are effective for the heteroatom Diels-Alder reaction. Indium trichloride (InCls) is a good catalyst for imino-Diels-Alder reactions. Hetero-Diels-Alder reactions involving carbonyls have been done in water. Ultrasound has been used to promote the Diels-Alder reactions of 1-azadienes. ... 

In the presence of 10 mol% of ytterbium triflate (Yb(OTf)3> a representative lanthanide triflate), N-benzylideneaniline (10a) was treated with 2-trimethylsi-loxy-4-methoxy-1,3-butadiene (Danishefsky s diene, 11) [59] in acetonitrile at room temperature. The imino Diels-Alder reaction proceeded smoothly to afford the corresponding tetrahydropyridine derivative in a 93% yield (Table 19). The adduct was obtained quantitatively when Sc(OTf)3 was used as a catalyst. Imines 10b and 10c also reacted smoothly with 11 to give the corresponding adducts in high yields. The reaction of 10a with cyclopentadiene was performed under the same reaction conditions. It was found that the reaction course changed in this case and that a tetrahydroquinoline derivative was obtained in a 69% yield. In this reaction, the imine worked as an azadiene toward one of the double bonds of cyclopentadiene as a dienophile [43,60]. In the reactions of 2,3-dimethylbutadiene, mixtures of tetrahydropyridine and tetrahydroquinoline derivatives were obtained. 

Thus, a new type of Lewis acid, lanthanide triflates, is quite effective for the catalytic activation of imines, and has achieved imino Diels-Alder reactions of imines with dienes or alkenes. The unique reactivities of imines which work as both dienophiles and azadienes under certain conditions were also revealed. Three-component coupling reactions between aldehydes, amines, and dienes or alkenes were successfully carried out by using Ln(OTf)3 as catalysts to afford pyridine and quinoline derivatives in high yields. The triflates were stable and kept their activity even in the presence of water and amines. According to these reactions, many substituted pyridines and quinolines can be prepared directly from aldehydes, amines, and dienes or alkenes. A stepwise reaction mechanism in these reactions was suggested from the experimental results. 

Two general approaches to aza-Diels-Alder reactions have been reported. One incorporates the requisite nitrogen atom into the 2rt component (imine), while the other incorporates the requisite nitrc en in the 4rt component (azadiene). Chiral copper Lewis acids have been used with success in both approaches. Jorgensen and coworkers reported enantioselective imino Diels-Alder reactions catalyzed by CuC104 MeCN in the presence of phosphino-oxazoline (287) or BINAP (290) (Scheme 17.64) [93]. Phosphino-oxazoline (287) proved to be the ligand of choice in the aza-Diels-Alder reaction of N-tosyl a-imino ester (142) with Danishefsky s diene (286), while BINAP (290) gave the highest selectivity when dimethyl-substituted Danishefsky s diene (289) was used. 

Yadav et al. had also reported their work on the imino Diels-Alder reaction catalyzed by InCh [188]. However, the various azadienes were generated in situ through reactions of DHP and aryl amines. DHP then acted as a dienophile for the subsequent pericyclic reactions with an endo preference for the examples studied (Figure 8.80). 

Fig. 8.80 Imino Diels-Alder reaction of azadiene formed in situ with DHP catalyzed by InCb.

The preparation of piperidines by cycloaddition can use either an imino (Scheme 13) or azadiene (Scheme 14) substrate. Highly functionalized tetrahydropiperidines were prepared by a high-pressure aza-Diels-Alder reaction <99TL1877>. The hetero [4+2] cycloaddition of vinyl... 

The Diels-Alder reaction of 1-azadienes has been used to construct indolizines and homologous systems. Hence, acyl azadienes (122), prepared by thermal elimination of acetic acid from N-acyl-O-acetyl-N-allylhydroxylamines, undergo intramolecular Diels-Alder cyclization to form indolizidine (123) and related ring systems. A closely related paper describes the synthesis of the indolizine ring system (124) by utilization of an imino Diels-Alder cyclization. 

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