Cooperativity in catalysis

25 Jan 2017. NUS chemists have discovered an operationally simple process to synthesise Z-enediyne, a potent class of anticancer warhead.

Z-enediyne, a type of molecule found in some natural products, has demonstrated great success in cancer cell destruction. This has generated significant interest among chemists to uncover new synthetic routes to produce Z-enediyne efficiently. Prof Zhao YU from the Department of Chemistry, NUS, together with his graduate student, have developed a single-step and operationally simple process to produce this valuable moiety (functional group of a molecule). They found that this can be produced by the trimerisation (a chemical process in which a molecular complex is made by combining three identical molecules) of commercially available alkynes, with the use of two catalysts (copper and palladium) concurrently.

Unlike previous reports on the synthesis of Z-enediyne, neither dangerous pyrophoric reagents nor the laborious synthesis of special reagents are required for this new method. This “mix-and-go” procedure simplifies the synthesis of Z-enediyne and generates minimum waste along the way. It minimises the use of hazardous substances and uses air as the oxidant, bearing the hallmarks of green chemistry.

In uncovering an attractive method for Z-enediyne synthesis, this breakthrough innovation by Prof Zhao Yu and his research team has the potential in speeding up the use of Z-enediyne as a possible drug candidate in the fight against cancer. Furthermore, in what was a bold move away from the traditional use of a single catalyst in reactions, this demonstration of seamless cooperation between two or more catalysts could provide the key to unlocking new frontiers in catalysis. This is aptly demonstrated in this work, where performing new chemical transformations on well-explored substrates like alkynes, remains very much a possibility!

In keeping with the overarching theme of developing simple catalytic systems to address key problems in chemistry, more cooperative catalysis protocols are currently being investigated by Prof Zhao’s research group.

Figure shows a reaction scheme for the intriguing trimerisation of alkynes to form Z-enediyne.

Reference

Lee JTD; Zhao Y*, “Access to Acyclic (Z)-Enediynes via Alkyne Trimerization: Cooperative Bimetallic Catalysis Using Air as the Oxidant” ANGEWANDTE CHEMIE INTERNATIONAL EDITION Volume: 55 Pages: 13872-13876 DOI:10.1002/anie.201608192 Published: 2016