Untethering sparteine: 1,3-diamine ligand for asymmetric synthesis in water

Chiral ligands are the toolbox for asymmetric synthesis to access 3D molecular world. Enabling efficient asymmetric reaction in water is a big challenge. As moisture/air stable and strong binding moieties, amines, compared to imine and phosphine ligands, are ideal candidates to accommodate asymmetric transformations in water. Known amine ligands like Proline analogues and Cinchona alkaloids showed excellent asymmetric induction. Sparteine, an alkaloid studied originated in 1968, had never been considered as a privileged catalyst due to its structure defection which led to poor reaction compatibility and unsatisfactory stereoselectivity. Here, we report the design of a chiral diamine catalyst untethering one of the sparteine rings. The diamine catalyst was easily accessed in two steps on 100 gram-scale. This chiral ligand was proved to be efficient for addition reactions in water providing products with excellent yields and enantiomeric ratios. This pluripotent catalyst has also shown good reactivity/enantioselectivity under organocatalysis, Cu and Pd-catalysed conditions. We anticipate that the ligand would allow further development of other catalysts for important yet challenging green stereoselective transformations.

Chiral Diamine in Small Molecule Biomimetic Asymmetric Catalysis

Enzymatic reaction, as an environmentally friendly approach, has made great progress producing commodity chemicals comparing to the conventional metallo/organo catalysis. However, the reaction compatibility is not satisfactory. The development of biomimetic catalysis balancing both strategies for the green and broad application in synthesis is desirable. Here, we report the design and synthesis of a chiral diamine catalyst fulfilling this requirement. Asymmetric addition reactions using this ligand in water were demonstrated and the corresponding products were produced in excellent yields and enantiomeric ratios. This pluripotent ligand has also shown good reactivity/enantioselectivity on a number of representative reactions in both green and organic solvents. We anticipate that the ligand would allow further development of other catalysts for important yet challenging green stereoselective transformations.

Organocatalysis for the Asymmetric Michael Addition of Cycloketones and α, β-Unsaturated Nitroalkenes

Michael addition is one of the most important carbon–carbon bond formation reactions. In this study, an (R, R)-1,2-diphenylethylenediamine (DPEN)-based thiourea organocatalyst was applied to the asymmetric Michael addition of nitroalkenes and cycloketones to produce a chiral product. The primary amine moiety in DPEN reacts with the ketone to form an enamine and is activated through the hydrogen bond formation between the nitro group in the α, β-unsaturated nitroalkene and thiourea. Here, the aim was to obtain an asymmetric Michael product through the 1,4-addition of the enamine to an alkene to form a new carbon–carbon bond. As a result, the primary amine of the chiral diamine was converted into an enamine. The reaction proceeded with a relatively high level of enantioselectivity achieved using double activation through the hydrogen bonding of the nitro group and thiourea. Michael products with high levels of enantioselectivity (76–99% syn ee) and diastereoselectivity (syn/anti = 9/1) were obtained with yields in the range of 88–99% depending on the ketone.