“Chemoselective C-C/C-N Bond Formation Reactions”

N-Arylpyridine-2-ones are a ubiquitous moiety present in many bioactive compounds and pharmaceutical drugs. Due to their intriguing biological activities such as antifibrotic, anti-inflammatory, anticonvulsant, and sedative activities, several copper-catalyzed coupling reactions for C-N bond formation between 2-pyridones and electrophiles such as aryl boronic acids, aryl stannanes, aryl bismuth, and aryl halides have been previously reported. Herein, to explain the viability of diaryliodonium salts as an electrophilic coupling partner, we report copper-catalyzed C-N bond formation using 2-pyridone derivatives at room temperature.

Heterocycles including pyridine are one of the most widely studied classes. Pyridine and its derivatives are easily found in natural products and of great importance in synthetic chemistry, pharmaceutical and agrochemical research. Therefore, numerous synthetic methods have been reported to form functionalized pyridines. Palladium catalyzed cross coupling reaction is one of the most convenient and versatile method for the preparation of trisubstituted pyridines from polyhalogenated pyridines. Therefore, chemoselective Suzuki-Miyaura reactions on 3,5- and 4,6-dibromo-2-tosyloxypyridine have been studied. The optimized conditions allow for a facile access to 3,5- and 4,6-diaryl-2-tosyloxypyridines in yields of 8 to 99%. Further functionalization of the tosylate group in the diarylpyridine derivatives obtained was accomplished for the synthesis of novel and biologically relevant trisubstituted pyridines. The formal synthesis of ficuseptine has also been achieved in 5 steps from 3,5-dibromo-2-hydroxypyridine with 50% overall yield.

Finally, we employed the benzyne intermediate formed by 1,3-silyl group migration on the aryl moiety to demonstrate metal-free C-N bond formation. This base-promoted benzyne formation method would be used for the synthesis of 3-aminophenol or carbazole derivatives, which are the scaffold of some synthetic compounds with various pharmacological activities.

20170525_세미나_Prof. Wonsuk Kim.pdf