Titanium-Mediated Domino Cross-Coupling/Cyclodehydration and Aldol-Addition/Cyclocondensation: Concise and Regioselective Synthesis of Polysubstituted and Fused Furans

Abstract

Titanium enolates, in situ-generated from readily available ketones and titanium tetraisopropoxide, undergo domino cross-coupling/cyclodehydration or domino Aldol-addition/cyclocondensation with α-chloroketones to provide synthetically valuable furan derivatives. The domino process tolerates a variety of cyclic and acyclic ketones and chloroketones, producing polysubstituted furans and bi-, tri-, and tetracyclic fused furans.

Cobalt(II)-Catalyzed Synthesis of γ-Diketones from Aryl Alkenes and Its Utilization in the Synthesis of Various Heterocyclic Compounds

“…Additionally, compound 3m also reacts with triflic acid (TfOH) in an acetonitrile solution to furnish 2-phenyl-4,5,6,7-tetrahydrobenzofuran ( 8 ) in 60% yield. All of the following postmodified heterocyclic compounds are widely known as invaluable scaffolds to demonstrate biological activities such as antimicrobial, , anti-inflammatory, anticancer, antifungal, and antiplasmodial activities.…”

“…One of the major advantage is that the reaction is carried out at room temperature with a broad substrate scope and produces a significant amount of the desired product employing inevitable postmodifications, especially five-or six-membered heterocyclic compounds that are significantly biologically important. 18 Several control reactions have been performed along with a primary kinetic isotope effect (PKIE) study to elucidate the rate-determining step, a radical scavenger experiment to define the mechanistic pathway of this oxidative coupling, and a Hammett analysis to determine the electronic factor during this following transformation. Moreover, density functional theory (DFT) calculations have also been performed to understand the details of mechanistic intricacies involved in the synthesis.…”

“…This synthetic route represents an eco-friendly methodology, avoiding any type of metal–ligand complex, additive, or co-catalyst, and using cheap, nontoxic, easily accessible metal salt. One of the major advantage is that the reaction is carried out at room temperature with a broad substrate scope and produces a significant amount of the desired product employing inevitable postmodifications, especially five- or six-membered heterocyclic compounds that are significantly biologically important . Several control reactions have been performed along with a primary kinetic isotope effect (PKIE) study to elucidate the rate-determining step, a radical scavenger experiment to define the mechanistic pathway of this oxidative coupling, and a Hammett analysis to determine the electronic factor during this following transformation.…”

Synthesis of Polysubstituted Furans: An Update Since 2019

“…Combining the ideas on the previous reports of the synthesis of furans, [71][72][73] Tang et al in the year 2022 exposed a titanium-mediated convergent synthesis of polysubstituted and fused furans from monoketones and α-haloketones via domino cross-coupling/cyclodehydration in moderate to excellent yields. [74] Mechanistically, the ketone 96 is prone to form a titanium enolate 98 in the presence of titanium tetraisopropoxide under high temperature and high concentration conditions. Then, the α-chloroketone 97 is attacked by the insitu generated stabilized enol in a domino Aldol-addition/cyclocondensation pathway.…”

Progress in Electrochemically Empowered C−O Bond Formation: Unveiling the Pathway of Efficient Green Synthesis

“…[4][5] Furthermore, carbonyl functional group C(sp 2 )-O in the aldehyde, ketone, ester, and acyl CÀ O bond can be generated via classical (Figure 1) and non-classical pathways (e. g., Vilsmeier reaction, Metal catalyzed carbonylation, oxidation of alcohol, allylic oxidation using metal etc.). [6][7][8] On the other hand, ester bond can be generated via non-classical pathway without prior activation of carboxylic group or via metal catalyzed crosscoupling reactions. [3] In addition, the acyclic version of C(sp 3 )-O bondin ethers have been conventionally synthesized via Williamsons reaction, metal catalyzed cross coupling of arylhalides with different alcohols etc.…”