Facile Synthesis of 2,5-Disubstituted Thiazoles from Terminal Alkynes, Sulfonyl Azides, and Thionoesters

Abstract

A sequential procedure for the synthesis of 2,5-disubstituted thiazoles from terminal alkynes, sulfonyl azides, and thionoesters is reported. A copper(I)-catalyzed 1,3-dipolar cycloaddition of terminal alkynes with sulfonyl azides affords 1-sulfonyl-1,2,3-triazoles, which then react with thionoesters in the presence of a rhodium(II) catalyst. The resulting 3-sulfonyl-4-thiazolines subsequently aromatize into the corresponding 2,5-disubstituted thiazoles by elimination of the sulfonyl group.

N-Propargylamines: versatile building blocks in the construction of thiazole cores

“…Among them, the Hantzsch thiazole synthesis (condensation of α-haloketones with thioamides) is the most efficient and straight forward procedure [34–43]. However, the general applicability of this method is limited by the narrow substitution patterns [31], by the harsh reaction conditions [26,30] or both. Therefore, methods that overcome these drawbacks are required.…”

Base‐Promoted Metal‐/Oxidant‐Free Three‐Component Tandem Annulation: A Strategy for the Construction of 2,4,5‐Trisubstituted Thiazoles via C−N Bond Cleavage of Amidines

“…First, reaction of 1 a with 1.1 equiv of 2 a and 3 equiv of 3 a in CH 3 CN using KOH (4 equiv) as base at 70°C for 12 h, ethyl 4-phenyl-2-(phenylamino)thiazole-5-carboxylate (4a) was exclusively obtained in 14% yield (Table 1, entry 1). Subsequently, during the screening of solvents, DMF, DMSO, EtOH, CH 2 Cl 2 and toluene were found to be inferior to CH 3 CN (entries [13][14][15][16][17]. In contrast to K 2 CO 3 , other organic bases including t-BuOK, Et 3 N, DBU and DABCO failed to enhance the yields of 4 a (entries 8-11).…”

“…Representative strategies include the following: (1) Lawesson's reagent mediated chemoselective enamides thionation-cyclization of fuctionalized enamides (Scheme 1a); [14] (2) Brønsted acid cyclization of trisubstituted propargylic alcohols with thioamides (Scheme 1b); [15] (3) a three-step sequence synthesis of thiazole derivatives from substituted methyl benzoates (Scheme 1c). [17] Although these methods have proven effective for the synthesis of 2,4,5-trisubstituted thiazoles, they suffer from the disadvantages of using unavailable starting materials, transition metal catalysts, or requiring microwave-irradiation and multistep reactions. [17] Although these methods have proven effective for the synthesis of 2,4,5-trisubstituted thiazoles, they suffer from the disadvantages of using unavailable starting materials, transition metal catalysts, or requiring microwave-irradiation and multistep reactions.…”

An Expeditious Route to trans‐Configured Tetrahydrothiophenes Enabled by Fe(OTf)3‐Catalyzed [3+2] Cycloaddition of Donor–Acceptor Cyclopropanes with Thionoesters

“…[13] Efficient synthesis of heteroaromatic compounds from thionoesters is also well investigated. [14] Thus, we focusedo n Scheme 1. [3+ +2] Cycloaddition reactionso fD-A cyclopropanes and dipolarophiles.…”