Facile synthesis of alkynyl‐, aryl‐ and ferrocenyl‐substituted pyrazoles via Sonogashira and Suzuki–Miyaura approaches

Abstract

A concise and efficient synthesis of densely substituted novel pyrazoles with alkynyl, aryl and ferrocenyl functionalities is reported, providing a platform for biological studies. The general strategy involves Sonogashira and Suzuki–Miyaura cross‐coupling reactions of easily obtainable 5‐ferrocenyl/phenyl‐4‐iodo‐1‐phenylpyrazoles with terminal alkynes and boronic acids, respectively. The starting 4‐iodopyrazoles were synthesized by electrophilic cyclization of α,β‐alkynic hydrazones with molecular iodine. Sonogashira reactions have been achieved by employing 5 mol% PdCl2(PPh3)2, 5 mol% CuI, excess Et3N and 1.2 equiv. of terminal alkyne, relative to 4‐iodopyrazole, in tetrahydrofuran at 65 °C, while Suzuki–Miyaura reactions have been accomplished using 5 mol% PdCl2(PPh3)2 and 1.4 equiv. of both boronic acid/ester and KHCO3, with respect to 4‐iodopyrazole, in 4:1 dimethylformamide–H2O solution at 110 °C. Both Sonogashira and Suzuki–Miyaura coupling reactions have proven effective for the synthesis of alkynyl‐, aryl‐ and ferrocenyl‐substituted pyrazoles and demonstrated good tolerance to a diverse range of substituents, including electron‐donating and electron‐withdrawing groups. These coupling approaches could allow for the rapid construction of a library of functionalized pyrazoles of pharmacological interest. Copyright © 2016 John Wiley & Sons, Ltd.

Synthesis of Thiophene/Furan‐Artemisinin Hybrid Molecules

“…When Sonogashira coupling reactions was used, o ‐alkynylthioanisole was obtained after new C−C bond formation, then iodocyclization reactions gave the corresponding 3‐iodobenzothiophenes with high yields. After isolation of 1 , Pd‐catalyzed Suzuki–Miyaura [26] coupling reaction was performed to synthesis of aldehyde derivatives ( 3 and 5 ). Recently, we investigated a new coupling procedure for the formation of aldehyde derivatives.…”

Fast and Efficient Continuous Flow Method for the Synthesis of Ynones and Pyrazoles

“…phile [14] derivative (an α, -unsaturated aldehyde/ketone, an allenic ketone, or a -alkynyl ketone) with hydrazine. [15] Because of their wide biological activity, [16] the challenge remains to develop new synthetic routes for the rapid and regioselective [17] assembly of substituted pyrazoles from simple and readily available starting materials. [18] In this context, when compared with batch techniques, continuous flow chemistry has many attractive features: enhancing mass-and heat-transfer, minimizing reaction volumes, and improving the degrees of sample-and reagent-mixing.…”

“…[3d], Pyrazoles five‐membered‐ring compounds having two adjacent nitrogen atoms are particularly interesting because of their wide physiological activities; for example, cyenopyrafen and pyrazolynate are pesticides and celecoxib is a nonsteroidal anti‐inflammatory agent . The general synthetic method for accessing a pyrazole ring is through [3+2] cycloaddition of a 1,3‐dielectrophile derivative (an α,β‐unsaturated aldehyde/ketone, an allenic ketone, or a β‐alkynyl ketone) with hydrazine . Because of their wide biological activity, the challenge remains to develop new synthetic routes for the rapid and regioselective assembly of substituted pyrazoles from simple and readily available starting materials .…”