Nanotechnologies / Materials
Organic synthesis, Drug discovery

Stereospecific cyanodifunctionalization of alkenes
Department of Applied Chemistry, Graduate School of Engineering
Assistant Professor Kensuke Kiyokawa
https://researchmap.jp/kensukekiyokawa?lang=en

Abstract
Stereospecific syn-oxycyanation of alkenes with p-toluenesulfonyl cyanide (TsCN) was achieved by utilizing a boron Lewis acid,tris(pentafluorophenyl)borane (B(C6F5)3), as a catalyst. Furthermore, when cyanogen bromide was used as a reagent, stereospecific syn-bromocyanation takes place. These developed methods
for the stereospecific difunctionalization of alkenes enable the efficient one-step synthesis of valuable nitriles from readily available
alkenes.

Nanotechnologies / Materials▍ Background & Results
This research significantly expands the synthetic applicabilityof the cyanodifunctionalization of alkenes, which was previously
limited to reactions with more reactive alkynes and intramolecularreactions. Furthermore, the developed method can provide valuable synthetic intermediates, β-hydroxynitriles and β-bromonitriles,
providing powerful tools for the synthesis of pharmaceuticals andfunctional materials.

▍ Significance of the research and Future perspective
The technique of introducing functional groups into organic
compounds is an important method for synthesizing functionalcompounds such as pharmaceuticals and functional materials. A
cyano group is a useful functional group that can be transformed

into various functional groups such as carboxyl and amino groups.
Therefore, the development of the method for introducing a cyanogroup into organic compounds has been actively investigated. The
cyanofunctionalization of carbon–carbon multiple bonds of readily
available alkenes, which can be used in the one-step synthesis offunctionalized compounds that would be valuable synthetic intermediates.
In this research, stereospecific syn-oxycyanation of alkenes with
p-toluenesulfonyl cyanide (TsCN), providing β-hydroxynitriles, wasachieved by utilizing a boron Lewis acid, tris(pentafluorophenyl)
borane (B(C6F5)3), as a catalyst. Although several methods for synthesizing β-hydroxynitriles from alkenes have been reported, they
typically require multiple steps and/or harsh reaction conditions,making them less practical. The reaction developed in this study isa one-step process and surpasses conventional methods because
it is applicable to a wide range of substrates with diverse functionalgroups. Furthermore, when cyanogen bromide was used as a reagent, stereospecific syn-bromocyanation takes place.
This study significantly expands the applicability of the cyanodifunctionalization of alkenes, which was previously limited tomore reactive alkynes and intramolecular reactions. The developed methods allow an efficient one-step synthesis of valuable
nitriles from readily available alkenes. Furthermore, the reaction
mechanism of the stereospecific oxycyanation, in which B(C6F5)3
effectively contributes to the stabilization of the transition state, waselucidated by spectroscopic analyses and DFT calculations.

P a t e n t
Kiyokawa, Kensuke; Ishizuka, Miu; Minakata, Satoshi. Stereospecific oxycyanation of alkenes with sulfonyl cyanide. Angew. Chem. Int. Ed. 2023, 62,e202218743. doi:10.1002/anie.202218743
Kiyokawa, Kensuke; Noguchi, Ikumi; Minakata, Satoshi et al. Tris(pentafluorophenyl)borane-catalyzed stereospecific bromocyanation of styrene derivatives
with cyanogen bromide. Org. Lett. 2023, 25, 2537–2542. doi:10.1021/acs.orglett.3c00727
UR
L http://www.chem.eng.osaka-u.ac.jp/~minakata-lab/english/index.html
K e y w o r d organic synthesis, catalytic reaction, functionalized compounds, nitriles
Tr e a t i s e