Investigation On The Asymmetric Organocatalytic [5+1]Double Michael Addition Reactions

1. Synthesis of Some Chiral Catalysts Derived From Cinchona Alkaloids and Chiral1,1’-bi-2-Naphthol (BINOL).Asymmetric organocatalysis has become a powerful tool for the synthesis of optically active compounds. Herein we synthesized some classic organocatalysts according to the literatures such as cinchona derived primary amines, bifunctional thioureas, cyclohexanediamine derived thioureas and chiral1,1’-bi-2-naphthol (BINOL)-derived phosphoric acids. Subsequently, we investigated some asymmetric conjugated additions especially Michael additions in the presence of these catalysts.2. Asymmetric Synthesis of Optically Active4-Nitro-Cyclohexanones through Bifunctional Thiourea-base Catalyzed [5+1] Double Michael Addition ReactionsThe construction of suitably functionalized cyclohexanone derivatives plays an important role in the synthesis of many natural products with significant biological and pharmaceutical activities.We found thiourea-modified cinchona alkaloids as bifunctional catalysts and a base could catalyze a stepwise [5+1] cyclization of divinyl ketones with nitromethane via double Michael additions, furnishing optically active4-nitro-cyclohexanones with good yields, excellent diastereoselectivities (>20:1) and high stereoselectivities (up to94%ee).3. Synthesis of Chiral Spiro[cyclohexanone-oxindoles] and Spiro [cyclohexanone-pyrazolones] through Cinchona Derived Primary Amine Catalyzed [5+1] Double Michael Addition ReactionsThe asymmetric catalytic synthesis of naturally occurring and biologically active spiro compounds is a challenge for modern chemical methodology.Here we reported the construction of spiro compounds through cascade [5+1] double Michael reactions between divinyl ketones and N-unprotected oxindoles or N-phenyl-protected pyrazolones catalyzed by a combination of the easily available9-amino-9-deoxy-epiquinine with N-Boc-D-phenylglycine. The desired multistereogenic spiro[cyclohexanone-oxindoles and-pyrazolones] were obtained with high yields (up to98%) and stereoselectivities (up to>20:1dr,99%ee).