Asymmetric Synthesis Of Polysubstitutedγ-Nitroketoncs And Tetrahyrothiophcncs Via Bifunctonal Organoatalysis

Since the seminal work pioneered by List, MacMillan and Jacobsen groups, metal-free catalytic systems, namely, organocatalysis has become the third pillar in the realm of asymmetric catalysis. Over the past decade, fruitful achievements have been reached concerning the development of new activation modes, new catalysts, novel reaction design and catalysis-based natural products synthesis. In this context, bifunctional organocatalysis has received considerable attention due to the superior abilitiy toward synergetic activation of both reaction patners. This chapter focus on the a decade upate of the representative works in the field of bifunctional Br(?)nsted base-Br(?)nsted acid, Lewis base-Br(?)nsted acid and Lewis base-Lewis acid organocatalysis.The functionalized γ-nitroketones are versatile building blocks for the synthesis of γ-amino acid, nitrogen-containing heterocycles and alkloids. Herein we presented a quinine-derived bifunctional tertiary-primary diamine catalyzed conjugate addition of nitroalkene to simple enones, affording the terminal alkene containing γ-nitroketones in a highly enantioselective manner. Owing to the synthetic value of the nitro, alkene and carbonyl group, this chemistry hold great potential for the library synthesis of structurely complex and stereochemically diverse N-heterocycles.The development of organocatalyzed cascade reactions attracted continuing efforts owing to their ability toward facile and stereoselectively assembly of complex and diverse molecules as well as their operational simplicity and environmental friendliness. To our knowledge, there is no precedent for noncovalent interaction mediated cascade reaction of chalcones. Polysubstituted tetrahydrothiophenes are present in a large number of nature products and bioactive molecules and also are widely used as ligands and organocatalysts. Herein, we developed a bifunctional squaramide catalyzed sulfa-Michael/aldol cascade reaction using chalcones as reaction patners for the direct assembly of trisubstited tetrahydrothiophenes. The chemistry features moderate to high yield, high diastereo-and enantiocontrol, relatively low catalyst loading and remarkable temperature effect upon the reaction efficiency.Among fluorinated molecules, trifluoromethylated-molecules always display remarkable biological activities and received considerable attention. Furthermore, the asymmetric construction of quartnary stereocenters is a long-standing challenge in modern organic chemistry. Based on our previous work, we developed a bifunctional squaramide catalyzed sulfa-Michael/aldol cascade reaction between1,4-dithiane-2,5-diol and β-aryl-β-trifluoromethylated enones. The trisubsttituted tetrahydrothiophenes with a trifluoromethylated quaternary stereocenters can be efficiently achieved with high stereocontrol.