Tandem aza ene type reaction

In 2007, Terada et al. extended their previously described chiral phosphoric acid-catalyzed aza-ene-type reaction of M-acyl aldimines with disubstituted enecarbamates (Scheme 28) to a tandem aza-ene-type reaction/cyclization cascade as a one-pot entry to enantioenriched piperidines 121 (Scheme 48). The sequential process was rendered possible by using monosubstituted 122 instead of a disubstituted enecarbamate 76 to produce a reactive aldimine intermediate 123, which is prone to undergo a further aza-ene-type reaction with a second enecarbamate equivalent. Subsequent intramolecular cychzation of intermediate 124 terminates the sequence. The optimal chiral BINOL phosphate (R)-3h (2-5 mol%, R = 4-Ph-C H ) provided the 2,4,6-sub-stituted M-Boc-protected piperidines 121 in good to exceUent yields (68 to > 99%) and accomplished the formation of three stereogenic centers with high diastereo- and exceUent enantiocontrol (7.3 1 to 19 1 transicis, 97 to > 99% ee(trans)) [72]. 

Scheme 48 Tandem aza-ene-type reaction/cyclization cascade scope and reaction intermediates...

In related studies, Terada described the synthesis of optically pure piperidines via a tandem aza-ene-type reaction/cyclization sequence (Scheme 5.18) [32]. The reaction of a monosubstituted enecarbamate and an N-acyl aldimine affords aza-ene-type intermediate 5, which reacts with a second equivalent of enecarbamate to give aldimine 6. Subsequent intramolecular cyclization terminates the aze-ene-type reaction sequence to furnish trans-piperidine 7 in high enantio- and diasterio-selectivities. 

Cascade Transformations Based on Tandem Aza Ene-Type Reaction... 

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