Synthesis of various N-heterocycles with perfluoroalkyl groups for creating a perfluoroalkyl compound library
November 9, 2017
Organic compounds with perfluoroalkyl groups (perfluoroalkyl compounds) have promise for pharmaceutical and agricultural lead compound development. Excellent lead molecules could be found efficiently if physiological activity could be evaluated using a chemical library of perfluoroalkyl compounds. However, constructing such a library requires a highly practical synthetic method for perfluoroalkyl compounds that is cost-effective, safe and efficient. Such a method had remained elusive.
The RIKEN Sodeoka Synthetic Organic Chemistry Laboratory and RIKEN CSRS have developed such a method using easily available and low-cost perfluoro acid anhydride as the perfluoroalkyl source, allowing N-heterocycle–forming perfluoroalkylation of aminoalkenes. Additionally, the use of a copper catalyst controls selectivity, making possible the synthesis of versatile perfluoroalkylated N-heterocycles. By derivatizing the obtained products, researchers also succeeded in converting them to more complex building block molecules. Since N-heterocycles are found in the main building blocks of bioactive molecules, the obtained compounds are considered to be hybrid molecules with the advantages of both perfluoroalkyl groups and N-heterocycles.
It is expected that these practical and excellent results will contribute to the construction of high-quality compound libraries and the search for new bioactive molecules.
The Journal of Organic Chemistry doi:10.1021/acs.joc.7b02307
S. Kawamura, K. Dosei, E. Valverde, K. Ushida, M. Sodeoka,
"N-Heterocycle-forming amino/carboperfluoroalkylation of aminoalkenes by using perfluoro acid anhydrides: mechanistic studies and applications directed toward perfluoroalkylated compound libraries".
Shintaro Kawamura; Research Scientist
Mikiko Sodeoka; Group Director
Catalysis and Integrated Research Group