March 2024

We report improved protocols for the synthesis of thiazolium precatalysts from primary amines, carbon disulfide, and α-halo ketones. For N-alkyl-substituted derivatives, yields of the corresponding thiazolethiones can be dramatically improved by isolating the intermediate dithiocarbamates. In most cases, meta-chloroperbenzoic acid can advantageously replace H2O2 in acetic acid for the oxidation of thiazolethiones into thiazoliums. This approach was applied to the synthesis of a thiazolium featuring a 2-adamantyl N-substituent, the corresponding persistent carbene, and its dimer.

Functionalized 1,2,4,5-tetrasubstituted benzenes are synthetically difficult or laborious to access. The Rh-catalyzed [2+2+2] cycloaddition of a diyne and internal alkyne offers a seemingly straightforward route to these scaffolds; however, this has been largely restricted to alkynes bearing activating (coordinating) functional groups, with very few examples of unactivated alkynes. In this work, we disclose an assessment of Rh-catalyzed [2+2+2] cycloadditions employing unactivated internal alkynes, focusing on the structural diversity and compatibility of both alkyne and diyne components. The limitations of this method are disclosed, with exceptionally bulky alkynes and specific functional groups undergoing side reactions. Furthermore, the practicalities of gram-scale reactions and catalyst recovery/reuse are demonstrated.

We have developed a TfOH-catalyzed, highly efficient protocol for the synthesis of biologically active β-acylamino ketones from aldehyde, ketone, and nitrile by avoiding the use of acetyl chloride. The reaction proceeds through a sequential aldol reaction followed by a nucleophilic attack of nitrile and hydrolysis of nitrile in one pot. The attractive features of this tandem process are mild reaction conditions, high atom economy, broad substrate scope with 51–87% yield, gram-scale reaction, and ease of operation.