Sequential SNAr Reaction/Suzuki-Miyaura Coupling/C−H Direct Arylations Approach for the Rapid Synthesis of Tetraaryl-Substituted Pyrazoles

• Published in: Chemistry, an Asian journal Vol. 10; no. 8; pp. 1626 - 1630
• Main Authors: Morita, Taiki, Kobayashi, Daisuke, Matsumura, Keisuke, Johmoto, Kohei, Uekusa, Hidehiro, Fuse, Shinichiro, Takahashi, Takashi
• Format: Journal Article
• Language: English
• Published: Weinheim Blackwell Publishing Ltd 01.08.2015; Wiley Subscription Services, Inc
• Subjects: C-H activation; Chemistry; cross-coupling; heterocycles; palladium; synthetic methods
• ISSN: 1861-4728; 1861-471X
• DOI: 10.1002/asia.201500362

A rapid synthesis of 1,3,4,5‐tetraaryl‐substituted pyrazoles has been achieved through a sequence of SNAr reaction/Suzuki–Miyaura coupling/Pd‐catalyzed direct arylations that used 3‐iodo‐1H‐pyrazole as a scaffold. Pyrazoles with four different aryl groups were synthesized in a straightforward manner with no extra synthetic steps, such as protection/deprotection or the introduction of activating/directing groups, using readily available substrates and reagents. The developed synthetic approach enabled the structurally diverse synthesis of multiaryl‐substituted pyrazoles without using a glovebox technique. Cote dpyrazole: A rapid synthesis of 1,3,4,5‐tetraaryl‐substituted pyrazoles has been achieved through a sequence based on a readily available 3‐iodo‐1H‐pyrazole scaffold; this sequence includes a SNAr reaction, Suzuki–Miyaura coupling, and C−H direct arylations. This is the first example of the synthesis of pyrazoles with four different aryl groups by four sequential cross‐coupling reactions.