DMSO as a C₁ Source for [2 + 2 + 1] Pyrazole Ring Construction via Metal-Free Annulation with Enaminones and Hydrazines

Abstract

A cascade reaction between enaminones, hydrazines, and dimethyl sulfoxide (DMSO) for the synthesis of 1,4-disubstituted pyrazoles catalyzed by molecular iodine in the presence of Selectfluor has been realized. DMSO plays a dual role as the C1 source and the reaction medium. In addition, the synthesis of 1,3,4-trisubstituted pyrazoles using aldehydes as alternative C1 building blocks has also been achieved.

Recent advances in transition metal-free annulation toward heterocycle diversity based on the C–N bond cleavage of enaminone platform

“…Rather recently, the Wan group disclosed a novel synthetic protocol to access various pyrazoles by the three-component cascade reaction of enaminones, hydrazines and dimethyl sulfoxide initiated by I 2 and Selectfluor (Scheme 29). 59 In the I 2 /Selectfluor-promoted protocol, the I 2 -mediated transamination of enaminones with hydrazines was performed firstly to provide N -amino enaminones, and then electrophilic addition was proceed subsequently between the N -amino enaminones and fluorinated DMSO to give corresponding additional intermediates. Finally, an array of desired pyrazoles were generated by the elimination of HSOMe, intramolecular cyclization and subsequent aromatization.…”

Lewis Acid-Promoted Typical Friedel–Crafts Reactions Using DMSO as a Carbon Source

“…21 The title compound was prepared following GP1 using 1,2,3-trimethoxybenzene (1.0 mmol, 168 mg), TMSOTf (0.5 mmol, 92.5 μL), and DMSO (0.5 mL): yield 243 mg (70%); white solid; R f = 0.5 (SiO 2 , 8:2 hexane/ EtOAc); 1 H NMR (400 MHz, DMSO-d 6 ) δ 6.7 (d, J = 8.5 Hz, 2H), 6.6 (d, J = 8.5 Hz, 2H), 3.87 (s, 6H), 3.85 (s, 6H) 3.82 (s, 6H), 3.79 (s, 6H); 13 C{ 1 H} NMR (101 MHz, CDCl 3 ) δ 152. 1,151.8,142.3,127.3,124.4,107.1,60.7,55.9,29.2. 4,.…”

“…Diarylmethane (DAM)-based derivatives have played a special role in medicinal chemistry and in the development of supramolecular chemistry. 1 Furthermore, they are important structural motifs of several biologically active drugs with antifungal (clotrimazole) and anti-breast cancer (arudine) activity and an anticoagulant (dicoumarol) agent. 2a−c As a part of medicinal chemistry, these compounds have played a major role as GABA A receptor modulators and in compounds with anticancer and antibacterial activity.…”

Visible-light-mediated multi-component carbene transfer reactions of α-diazoesters to construct multisubstituted pyrazoles and 1,3-dicarbonyl derivatives

“…5 Consequently, a number of methods have been developed for the construction of multisubstituted pyrazoles. 6–10 Generally, pyrazoles are synthesized by the cyclocondensation of hydrazines with substituted 1,3-dicarbonyl compounds 7 and cycloaddition of diazo derivatives with alkenes or alkynes, 8 electrophilic cyclization of α,β-alkynic hydrazones, 9 etc . Recently, the direct functionalization of pre-existing pyrazolones has also developed as a powerful protocol for the preparation of multisubstituted pyrazoles.…”