A Study On Aza-Michael Reaction Of α-substituted Acrylaldehydes

Since the importance of aza-Michael reaction in organic synthesis, especially for the construction of C-N bond and the synthesis ofβ–aminocarbonyl compounds, it has received much attention in recent years. Meanwhile, with the emerging of the organocatalysis, we become more and more interested in the organocatalytic aza-Michael reaction.Firstly, threeα-substituted acrylaldehydes,α-phenoxyacrylaldehyde,α-benzyloxyacrylaldehyde andα-benzylacrylaldehyde were synthesized via the aldol reactions between the corresponding aldehydes and formaldehyde. In addition, 2-bromoacrylaldehyde was also prepared through the reaction of acrylaldehyde with bromine.Then we studied their aza-Michael reaction with imides, and found that triethylamine (TEA), triethylenediamine (DABCO) and quinine (10 mol%) could effectively catalyze the aza-Michael reaction of 4-nitrophthalimide to acrylaldehyde in acetonitrile. The yields reached to 97%, 79% and 92%, respectively.In contrast to 4-nitrophthalimide, the reactivities of phthalimide and succimide were much poor towards acrylaldehyde.In addition, 4-nitrophthalimide smoothly added toα-benzylacrylaldehyde and acrylaldehyde in the presence of quinine as the catalyst (10 mol%) in acetonitrile. After 12 h, the yields reached up to 94% and 92% respectively. However, the Michael acceptors such asα-phenoxyacrylaldehyde,α-benzyloxyacrylaldehyde and 2-bromoacrylaldehyde, which have a hetero-atom at the alpha positions, showed poor reactivities in the reactions with 4-nitrophthalimide.