Regioselective and Stereoselective Pd-Catalyzed Intramolecular Arylation of Furans: Access to Spirooxindoles and 5H-Furo[2,3-c]quinolin-4-ones

Abstract

Herein, we report regio- and stereoselective intramolecular direct arylations of N-(2-bromophenyl)-2-furancarboxamides 1 to produce spirooxindoles 2 and 5H-furo[2,3-c]quinolin-4-ones 3 under different reaction conditions. Specifically, in the presence of Pd(PPh) as a catalyst, PPh as a ligand, and KCO as a base, substrates 1 underwent intramolecular α-arylation, possibly via a Heck insertion pathway, to provide 2, with the Z-isomer being favored. When the base was t-BuOLi and R was an aryl group, the reaction favored E-2, possibly via an electrophilic palladation pathway. In contrast, in the presence of PdCl as a catalyst, (o-OMePh)P as a ligand, and PivOH as an additive, substrates 1 underwent intramolecular β-arylation to provide 3, possibly via a concerted metalation-deprotonation process.

Transition metal-catalyzed synthesis of spirooxindoles

“…In the same year, a method for the synthesis of spirooxindoles 127 catalyzed by Pd was put forward by the same group. 85 Here also derivatives of furan-derivative of 122 were utilized which underwent intramolecular arylation and transformed into spirooxindoles 127 with high stereo- and regioselectivity. The Z -isomer was formed in higher amount when the reaction of N -(2-bromophenyl)-2-furancarboxamides proceeded with 5 mol% Pd(PPh 3 ) 4 , 10 mol% PPh 3 and 200 mol% K 2 CO 3 in DCE at 80–90 °C ( Scheme 63 ).…”

Synthesis, Characterization, and Cytotoxicity of New Spirooxindoles Engrafted Furan Structural Motif as a Potential Anticancer Agent

“…Several structural pharmacophores have been coadministrated with the spirooxindole privileged structures inspired by research for structural complexities with their diverse bioactivities. , Due to the urgent need to discover a new cancer agent with more targeting to cancer cells and less harmful for the normal tissue, chemists have synthesized many spirooxindoles for this purpose. In particular, spirooxindoles containing furan scaffold, which are called oxa-spirooxindoles, widely exist in many natural and biologically active molecules. − The designed, synthesized, and reported spirooxindoles show anticancer activity and can serve as an anti-tumor agent, CB2 receptor agonist, antagonists of progesterone receptors, antagonists of progesterone receptors, Nav1.7 blocker (XEN907), and selective cyclooxygenase COX-1 with TNF-α and IL-6 Inhibitors. − …”

LiCl-Mediated and Palladium-Catalyzed Oxidative Cyclization of Furan–Ynes via Dearomatizing Alkoxyalkenylation of Furan

“…As a typical electron-rich aromatic ring, furans frequently serve as nucleophiles , or acceptors of Heck insertion in substantial transformations. Consequently, nucleopalladation-initiated cyclization of furan–ynes could be proceeded via two divergent patterns.…”