Nguyen’s group focuses their research on development of new synthetic methodologies in organic chemistry, organocatalysis and natural product synthesis.
Organocatalysis, chemical process catalyzed by small non-metallic organic compounds, has been attracting a great deal of attention from synthetic organic chemists for the last fifteen years as one of the most promising emerging fields in organic chemistry. It can be employed in diverse synthetic cascade sequences to quickly construct complex bonds, stereocenters and polycyclic frameworks. Organocatalysts are less expensive, more stable and exhibit superior solubility in both organic and aqueous solutions compared to organometallic/bioorganic counterparts. Most importantly, organocatalysis generally gives rise to outstanding stereoselectivity, which is significantly valuable and useful at the structural engineering stage of bioactive compounds and pharmaceutical agents.
Aromatic Cation Activation:
(Image by Demelza Lyons)
The Nguyen group is one of the first few groups utilizing non-benzenoid aromatic ions to promote organic reactions. A new method for the nucleophilic substitution of alcohols and carboxylic acids and other substrates using aromatic tropylium cation activation has been developed in our group recently. It demonstrates, for the first time, the synthetic potential of tropylium cations in promoting chemical transformations. (http://pubs.acs.org/doi/abs/10.1021/ol5003972 and http://pubs.rsc.org/en/Content/ArticleLanding/2015/CC/C4CC09539A).
Currently, several projects utilizing this system are running in the group. Please contact Vinh Nguyen directly for further details.
N-Heterocyclic Olefins (NHOs) as Organocatalysts
The Nguyen group is one of a few groups establishing this topical emerging research field. In recent decades, N-heterocyclic carbenes have become established as a prevalent family of organocatalysts. N-Heterocyclic olefins, the alkylidene derivatives of N-heterocyclic carbenes, have recently also emerged as efficient promoters for organic reactions. Their extraordinarily strong Lewis/Brønsted basicity suggests great potential as a new class of organocatalysts for a broad range of reactions in synthetic chemistry (see http://onlinelibrary.wiley.com/doi/10.1002/chem.201503575/abstract and http://pubs.acs.org/doi/abs/10.1021/acs.orglett.6b00835)
Other on-going organocatalytic projects
(for discussion on confidential research projects, please contact Vinh Nguyen directly)
Chiral super-Brønsted-base catalysts to promote asymmetric synthesis
The focus of Brønsted base organocatalysts has recently shifted from normal amines towards organic compounds with enhanced proton affinity, termed superbases. These superbase compounds include guanadines, phosphazenes and cyclopropenimines. However, to date there have been only a limited number of studies employing chiral superbase derivatives as catalysts for chemical transformations. This project aims to develop a new family of bifunctional chiral superbases with unique structural properties, which allow privileged transition state organization, to facilitate asymmetric Brønsted-base catalyzed chemical processes.
Organocatalytic Construction of Polycyclic Scaffolds for Synthesis of Natural Products
This project aims to investigate the construction of libraries of polycyclic compounds using organocatalytic cascade reaction sequences promoted by chiral primary and secondary amines. These polycyclic backbones would resemble the skeletons of numerous important bioactive natural occurring compounds, such as hydrophenanthrene natural products and steroids, thus allowing convenient access to the natural products as well as the development of biologically valuable compounds and new pharmaceutical agents.