Download Hung Anh Duong Project Synopsis

MEDIA STORY BANK: PROPOSALS TO RECEIVE FUNDING FROM THE GSK-SINGAPORE GREEN AND SUSTAINABLE MANUFACTURING PARTNERSHIP
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Novel approach
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CHEMICAL TRANSFORMATION
IRON-CATALYZED BIARYL COUPLING:
TOWARDS EFFICIENT, COST-EFFECTIVE
and ENVIRONMENTALLY FRIENDLY
PHARMACEUTICAL and FINE
CHEMICAL MANUFACTURING
Principal investigator: Dr. Hung Anh
Duong
Institution: Institute of Chemical and
Engineering Sciences (ICES)
Email: [email protected]
Website
Year of Award: 2013
Biaryls are ubiquitous in fine chemicals, agrochemicals,
pharmaceuticals and materials. A popular method to gain access to this type
of compound is via the Nobel Prize winning metal-catalyzed cross-coupling
reactions. While being the most-scaled technology for biaryl coupling, the
palladium-catalyzed Suzuki-Miyaura reactions are not without drawbacks.
Palladium is a precious metal, which poses a high risk to sustainable
sourcing. Due to its toxicity, there is a stringent requirement to reduce the
amount of palladium contaminants in active pharmaceutical ingredients
(API) to below 10 ppm for oral drug substances, which creates extra burden
in the purification processes. In addition, the organoboron component
employed requires rather laborious synthesis.
These inefficiencies can, however, be resolved by a direct Kumada
coupling approach using iron catalysis. Iron (Fe) is the most abundant metal
in the earth's crust with low toxicity. Kumada coupling allows for direct use
of the Grignard reagent generated in situ, leading to step reduction and
waste minimization. In addition, the cost effectiveness and non-toxicity of
magnesium renders Kumada coupling the method of choice for low-cost
synthesis and green biaryl coupling. As such, the essence of this proposal is
to develop sp2-sp2 cross-coupling reactions that can be carried out with Fe
catalysis and have the potential to be developed for eventual
industrialization.
This project will deliver a capability for green and
sustainable manufacturing in Singapore. This
capability will consist of:
a) New tools and methods: Specifically, the
development of iron based catalysts that can
effectively cross couple organometallic sp2 carbons
with halogen or other sp2 carbon electrophiles.
b) A technology transfer package for green and
sustainable biaryl coupling together with guidance
for their optimal use.
c) Trained scientists for the Singapore talent pool:
Specifically, 1 PhD student and 1 junior scientist (both
to be Singaporean or PR) will be trained in the area of
homogeneous catalysis and organometallic
chemistry.
d) A strong, synergistic working relationship between
A*STAR and NUS.
e) Publications in high impact international journals
and intellectual property.