The central theme of our research is synthetic organic and organometallic chemistry with a focus on the development of new synthetic methods based on transition metal catalysis and various aspects of transition metal mediated free radical chemistry and their application to the synthesis of biologically active molecules.
We are particularly interested in discovering new generic manifolds for activation of amide bonds. Beyond any doubt, selective manipulation of amides via transition metal catalysis is a fundamental challenge in organic synthesis due to the partial double bond character of amides (amide bond resonance of 15-20 kcal/mol). Since amides are the key building blocks of peptides and proteins and some of the most frequently used intermediates in pharmaceutical development, this research has a potential to transform the way organic chemists approach complex molecule synthesis with downstream applications in medicine, materials science and drug discovery.
In 2015, we have introduced a new concept for amide bond N-C activation. Specifically, we have proposed and validated that the amide bond N-C activation can proceed only if the bond has been distorted from planarity; i.e., in planar amides the metal insertion into the N-C amide bond is impossible due to the classic similarity to the double bond.
The group has developed generic manifolds for transition metal catalyzed amide bond activation (Nobel Prize in Chemistry, 2010, Heck, Suzuki & Negishi), including the first Suzuki ketone synthesis, Heck olefin synthesis, direct biaryl synthesis, and Suzuki biaryl synthesis by activation of inert amide N-C bonds using Pd-, Ni-, and Rh-complexes. We are currently investigating the use of new catalysts for selective amide bond activation. Ultimately, we envisage that this research will enable point-selective manipulation of amides in complex biological environments.
In collaboration with Prof. He group, in 2015, we have demonstrated that graphene-based materials can be employed as efficient carbocatalysts for Friedel-Crafts alkylation reactions with unactivated arenes via a generic isomerization mechanism. Discovered in 2004 and recognized by the 2010 Nobel Prize in Physics (Geim & Novoselov), graphene is the thinnest and the strongest material on Earth with unprecedented opportunities in organic synthesis. Ultimately, we envisage that this research will enable new concepts in metal-free carbocatalysis for catalytic carbon-carbon bond forming reactions with unprecedented activity, high recyclability and chemoselectivity tunable by the revolutionary graphene materials with engineered surface.
In 2015, our laboratory introduced a new concept for reductive cyclizations of unactivated aminoketyl radicals from cyclic imides using SmI2–H2O as a productive merger of ketyl and α-aminyl radicals via polarity reversal. The use of aminoketyl radicals in organic synthesis presents a significant challenge due to the difficulty of a direct electron transfer into the antibonding amide π* orbital. Aminoketyl radicals have been invoked in degradation of nucleobases and proposed as critical species in electron capture dissociation of peptides. Aminoketyl radicals constitute a formal merger of the highly nucleophilic and predominantly planar ketyl radicals with the highly stabilized and partially pyramidalized α-amino radicals, which offers a unique reactivity platform to apply these unconventional intermediates in radical chemistry. We are currently developing complex cyclization cascades to access biologically-active families of alkaloids in a general fashion. Ultimately, we envisage that this research will enable rapid synthesis of important nitrogen-containing frameworks by radical umpolung.
Non-planar molecules & other research
Furthermore, the group has active research programs in the area of broadly-defined radical chemistry, C-H activation, mechanistic physical organic chemistry and bioenzymatic synthesis. The group collaborates with physical, analytical, materials and polymer chemists to provide sustainable solutions to important socioeconomic problems by chemical synthesis.
1) Amide bond N-C activation
Org. Biomol. Chem. 2016, 14, DOI: 10.1039/c6ob00084c.
Org. Lett. 2016, 18, 796-799.
Angew. Chem. Int. Ed. 2016, 55, DOI: 10.1002/anie.201600919.
Angew. Chem. Int. Ed. 2015, 54, 14518-14522.
Org. Lett. 2015, 17, 4364-4367.
2) Graphene catalysis
J. Am. Chem. Soc. 2015, 137, 14473-14480.
ACS Nano 2016, 9, 2305-2315.
3) Aminoketyl radicals
Org. Lett. 2015, 17, 5144-5147.
Chem. Rev. 2014, 114, 5959-6039.
4) Conformation of nonplanar functional groups
J. Org. Chem. 2015, 80, 7905-7927.
Chem. Commun. 2015, 51, 6395-6398.
Chem. Rev. 2013, 113, 5701-5765.