Adding boron is anything but boring …

Photo Credit: Dr. Martha Morton and Dr. James Takacs join Suman Chakrabarty in the lab
by UNL Chemistry Thu, 05/16/2019 - 15:18
A team of Nebraska chemists’ new research demonstrates a new way to access chiral secondary benzylic boronic esters, progressing research and expanding horizons for medicinal chemistry.

Published March 14, 2019 in Chemical Science (Issue 18), the flagship journal of the Royal Society of Chemistry, the research found new pathways to access chiral secondary benzylic boronic esters.

For the last decade, the Takacs research group has been actively engaged in the directed-catalytic asymmetric hydroboration (CAHB) reactions of alkene substrates to generate functionalized chiral boronic esters. The chiral boronic esters serve as important synthetic intermediates in asymmetric synthesis of bioactive and drug molecules. The chiral boronic esters have been recently gaining interest as boron-based therapeutics continue to evolve.

While there are several methods to synthesize chiral boronic esters in previous research studies, significant limitations remain in terms of generality of the methods and their substrate scope. The research produced by the Nebraska chemists demonstrates a very general way to access chiral secondary benzylic boronic esters. The process developed utilizes a chiral rhodium catalyst under ambient conditions and with high atom economy overall. “In particular, we show that substrates bearing heterocyclic ring systems of high relevance in medicinal chemistry can undergo this reaction effectively and the generated products can undergo further stereospecific transformations that showcase the utility of the methodology developed,” said Suman Chakrabarty, Ph.D. candidate in the Department of Chemistry.

The results of this work will be of significant interest to medicinal chemists as it displays a way to access phosphonate-functionalized, chiral boronic esters that in themselves are a new class of molecules. This result can be used in the context of developing new drug candidates or in the context of asymmetric synthesis of chiral molecules.

The research, developed as a part of Chakrabarty’s Ph.D. dissertation, was assisted by various individuals involved with the Takacs Research Group. Prof. Hector Palencia from the University of Nebraska Kearney, and Ryan Carr, a former student in the Takacs lab, contributed to aspects of the research. Chakrabarty notes, “Most importantly, Prof. Martha Morton, Director of the Research Instrumentation Facility, helped a lot with several of the NMR experiments that were key to the mechanistic investigations carried out in this work.”

Prof. Takacs adds, “The team did a terrific job harnessing power of asymmetric catalysis to make a new class of boron-containing compounds readily available, and at least in my mind, again proved that adding boron is anything but boring!”

The team received support from the NIH National Institutes of General Medical Sciences under the grant R01 GM100101.