Synthesis of α-d-galactose-based azacrown ethers and their application as enantioselective catalysts in Michael reactions

Abstract

New chiral monoaza-15-crown-5 type macrocycles annelated to methyl 4,6-O-benzylidene-α-D-galactopyranoside have been synthesized. These crown ethers proved to be efficient catalysts in a few asymmetric reactions under mild phase transfer catalytic conditions. Michael adducts were formed with good to excellent enantioselectivities, so the addition of diethyl acetamidomalonate to β-nitrostyrene took place with up to 92% ee, while the reaction of diethyl acetoxymalonate with chalcones proceeded with up to 99% ee. Using diethyl bromomalonate as the nucleophile, the chiral cyclopropane derivatives were formed in up to 99% ee with the addition to chalcone, in up to 78% ee in the reaction with benzylidene malononitrile, and in up to 76% ee in the reaction with 2-benzylidene-1,3-diphenyl-1,3-propanedione applying α-D-galactoside-based crown ethers as the catalysts. In the Michael addition, the substituents of the chalcone had a considerable impact on the outcome of the reactions. Quantum chemical calculations have also been employed to evaluate the origin of the stereoselectivities.