Download Practical, Asymmetric Redox-Neutral Chemical Synthesis via Borrowing Hydrogen

NUS Graduate School for Integrative Sciences and Engineering
Research Project Write-up
Title of Project :
Practical, Asymmetric Redox-Neutral Chemical
Synthesis via Borrowing Hydrogen
Name of Supervisor :
ZHAO Yu
Contact Details:
Email: [email protected]
Telephone: 65-65167964
Short Description
Synthetic chemistry is considered to be the “central science” as it provides the toolbox for various
applied areas such as pharmaceuticals, chemical biology and material science. Due to resource
constraints, the current trend in synthetic chemistry is not simply about preparing molecules of specific
interest, but rather on how to prepare them in a highly efficient and economical manner. The concept of
“redox economy” which focuses on minimizing synthetic steps that only adjust the oxidation state of
the intermediates without generating structural complexity is an important consideration at the strategic
level for chemical synthesis, and redox-neutral transformations that circumvent such redundant
oxidation/reduction steps are highly sought after as environmentally benign and sustainable processes.
Scheme a illustrates the process for the production of amines, which are ubiquitous functionality in
pharmaceuticals and agrochemicals. Traditionally, amines can be produced from the more readily
available alcohols through a multi-step process involving oxidation of alcohol to ketone, condensation
with amine to imine followed by reduction. As both the oxidation and reduction steps in this process
utilize stoichiometric reagents, much waste is generated. The concept of “borrowing hydrogen” has
thus proven to be much more efficient: the alcohol starting material can be directly converted to the
amine product in one step without the need for any external reagent!
Recent research efforts in our group have led to the realization of the first enantioselective variant of
this reaction to convert readily available alcohols to chiral amines that are highly valuable in drug
development. Scheme b showcases one impressive example that the mixture of four isomers in the
alcohol starting material was converted to essentially one pure isomer of the chiral amine product! Two
catalysts utilized in this process include a chiral iridium complex and achiral phosphoric acid.
The focus of the future studies is to develop truly simple and efficient catalytic systems to realize
such transformations as well as more important ones. For example, the conversion of 1,2-diols (again
as a mixture of isomers) to diastereo- and enantiopure 1,2-diamines will be the holy grail of this area of
research. The realization of such processes will have a profound impact in academic research as well as
chemical industry.