Asymmetric Transformations of Nitriles and Malononitriles

Professor Huang, Zhongxing   (Project Coordinator (PC))

Wang Jun   (Co-Investigator)

Lyu Hairon   (Co-Investigator)

Quan Yangjian   (Co-Investigator)

36

2024-04-01

4024624

Asymmetric Transformations of Nitriles and Malononitriles

Organic Synthesis Asymmetric Catalysis Transition Metal Catalysis Chiral Phosphoric Acid Desymmetrization

Chemical SciencesOthers - Chemical Engineering

Physical Sciences (P)

C7001-23Y

Collaborative Research Fund (CRF) - Group Research Project 2023/2024

2024

On-going

1. This project aims to access chiral molecules with high complexity and functionality from active methylene compounds via distinct types of asymmetric catalysis. Transition metal, organic, and heterogeneous catalysts will be identified and optimized to enable asymmetric transformations of nitriles, carboxylic acids, and esters. The success of this project would produce a diverse collection of chiral building blocks from easily available starting materials. 2. We aim to develop a pair of desymmetric transformations of malononitriles. Chiral transition metal complexes and electron-deficient boron compounds are proposed to catalyze the reduction of one nitrile motif to give enantioenriched β-chiral amines, while a decyanative desymmetrization can be enabled by a metal-hydride species to give chiral nitriles. These chiral building blocks are expected to provide expeditious routes towards nitrogen- containing bioactive molecules, including drugs and agrochemicals. 3. An asymmetric decarboxylative protonation was also proposed to convert acid-containing active methylene compounds by using chiral acid or transition metal catalysts. As these acid reactants, such as aminomalonic acids and aminoacetoacetic acids, are easily accessible, the enantioselective decarboxylation could provide a rapid and modular approach towards multifunctionalized molecules, particularly amino acids. In addition, recyclable heterogeneous catalysts, especially those supported on polymers and metal-organic frameworks (MOFs), will be investigated for potential large-scale decarboxylation with low costs. 4. We also aim to enable an asymmetric ester reduction of multiple active methylene compounds by using the class of dinuclear zinc catalyst developed previously for the hydrosilylation of malonic esters. Instead of molecules with point chirality, reduction of diesters to enantioenriched allenes and atropisomers will be examined. Besides desymmetrization, the asymmetric hydrosilylation will also be applied to the (dynamic) kinetic resolution of nitrogen-containing active methylene compounds.