Asymmetric Intramolecular Aza-Michael Reaction Using Enviromentally Friendly Organocatalysis

This communication describes enantioselective intramolecular aza-Michael reaction to prepare 1,2,3,4-tetrahydroisoquinolines by using organocatalysts.The organocatalytic reaction offers new green chemical process in heterocyclic chemistry.Additional noting, both enantiomers of the product were easily synthesized by using two types of organocatalysts prepared from the same amino acid.Aza-Michael reaction has been intensely investigated as an important C-N bond formation reaction in the synthesis of heterocyclic compounds. 1Most of the cases a nitrogen nucleophile reacts with α,βunsaturated carbonyl function as either a neutral nitrogen or an anionic nitrogen such as metal amide base.However, due to the strong Lewis basicity of the neutral or anionic nitrogen, catalytic aza-Michael reaction utilizing Lewis acid catalysis must be a difficult task.We have supposed that utilization of organocatalysts can solve the inherent problems.During the past few years, asymmetric organocatalysis 2 (only small organic molecule used as a reaction catalyst) has received intensive interests from the viewpoint of green chemistry as well as bioorganic chemistry.Recently, MacMillan and co-workers have revealed that organocatalysts (1a) and/or (1b) are significantly effective in enantioselective reactions with α,β-unsaturated carbonyl compounds, such as Diels-Alder reaction, 3 1,3-dipolar addition 4 and Friedel-Crafts alkylation 5 (Figure 1).Through the asymmetric reactions the organocatalysts serves to activate the achiral Michael acceptor via formation of a chiral iminium species.It is noteworthy that MacMillan's process is very ecological; the reaction proceeds without metallic reagents/catalysts in