N-Heterocyclic Carbene-Catalyzed Cyclization of Aldehydes with α-Diazo Iodonium Triflate: Facile Access to 2,5-Disubstituted 1,3,4-Oxadiazoles

Abstract

Herein, we report a novel organocatalytic process for synthesis of complex 1,3,4-oxadiazoles from readily accessible aldehydes. By exploiting the nucleophilicity of the putative Breslow intermediate and the inherent electrophilicity of α-diazo iodonium triflate, we have found that N-heterocyclic carbene catalyst promotes efficient cyclization of various aldehydes and α-diazo iodonium triflates. The reaction proceeds under mild conditions with a wide range of functional group tolerance. The heterocyclic products can be readily further functionalized, rendering the protocol highly valuable.

Visible Light-Induced Coupling Cyclization Reaction of α-Diazosulfonium Triflates with α-Oxocarboxylic Acids or Alkynes

“…On the basis of the mechanistic investigations and related literatures, − , a plausible reaction mechanism for the formation of compounds 3 and 5 is proposed in Scheme . Initially, diazomethyl radical A and cation radical B are generated from α-diazosulfonium triflates 1 under the irradiation of blue light via homolytic S–C bond cleavage.…”

Copper-Catalyzed One-Pot Synthesis of 2,5-Disubstituted 1,3,4-Oxadiazoles from Arylacetic Acids and Hydrazides via Dual Oxidation

“… 15 Recently, Li Liu et al developed a novel approach to assemble 2,5-disubstituted 1,3,4-oxadiazoles from α-oxocarboxylic acids via a decarboxylative cyclization by photoredox catalysis using hypervalent (III) iodine as a catalyst ( Scheme 1 d). 16 Although these methods are impressive, still there are some drawbacks such as the presynthesis of starting materials, long reaction times, expensive ligands, reagents, and low yields. Therefore, facile and simple approaches for accessing an array of 2,5-disubstituted 1,3,4-oxadiazoles from easily available starting materials are highly desirable.…”

“…disclosed a metal- and base-free reaction to obtain 2,5-diaryl 1,3,4-oxadiazoles from aryl tetrazoles by N-acylation with aldehydes followed by thermal rearrangement (Scheme c) . Recently, Li Liu et al developed a novel approach to assemble 2,5-disubstituted 1,3,4-oxadiazoles from α-oxocarboxylic acids via a decarboxylative cyclization by photoredox catalysis using hypervalent (III) iodine as a catalyst (Scheme d) . Although these methods are impressive, still there are some drawbacks such as the presynthesis of starting materials, long reaction times, expensive ligands, reagents, and low yields.…”

Catalyst-Free Visible-Light-Promoted Cyclization of Aldehydes: Access to 2,5-Disubstituted 1,3,4-Oxadiazole Derivatives

“…During our investigation, one study on N-heterocyclic carbene-catalyzed cyclization of aldehydes with α-diazo iodonium triflate for the synthesis of 2,5-disubstituted 1,3,4-oxadiazoles was published (Scheme 1b). 12 The process undergoes nucleophilic addition of NHC to the aldehyde, Nselective nucleophilic attack of α-diazo ammonium triflate, and cyclization to afford various 1,3,4-oxadiazole derivatives. In continuation of our interest in the field of hypervalent iodine chemistry, herein, we disclose a simple and efficient approach for the preparation of 2,5-disubstituted 1,3,4-oxadiazoles via catalyst-free visible-light-promoted cyclization of aldehydes with hypervalent iodine(III) reagents.…”

“…Aldehydes are one of the acyl radical sources, which have abundant, readily available, and versatile intermediates. During our investigation, one study on N -heterocyclic carbene-catalyzed cyclization of aldehydes with α-diazo iodonium triflate for the synthesis of 2,5-disubstituted 1,3,4-oxadiazoles was published (Scheme b) . The process undergoes nucleophilic addition of NHC to the aldehyde, N-selective nucleophilic attack of α-diazo ammonium triflate, and cyclization to afford various 1,3,4-oxadiazole derivatives.…”