Mild Heterogeneous Thiophene Hydrogenation Enabled by a Modified Palladium Catalyst

Abstract

Abstract Thiophenes are readily available sulfur heteroarenes and prominent motifs in medicinal and synthetic chemistry, but their direct heterogeneous hydrogenation to thiolanes remains challenging due to sulfur-induced catalyst deactivation and competing hydrodesulfurization. Here, we report a chloroform-induced surface modification strategy that enables the heterogeneous Pd(OH)2/C-catalyzed hydrogenation of thiophenes to saturated sulfur heterocycles. The method proceeds under mild hydrogenation conditions and provides access to a range of alkyl-, silyl-, aryl-, and benzofused thiolane derivatives. A hydrogenation-focused robustness assessment revealed compatibility with several functional groups that are commonly sensitive under Pd/H2 conditions, while preparative scope studies showed that functional-group-containing thiophenes can be converted when potentially interfering motifs are separated from the thiophene core by suitable alkyl or aryl spacers. Mechanistic experiments indicate that CHCl3 is not merely a beneficial solvent: CHCl3/H2 pretreatment of Pd(OH)2/C generates a catalytically competent material whose activity is retained after replacing CHCl3 with 2-MeTHF. X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) analyses support the formation of persistent chloroform-derived organochlorine/C–Cl-type surface environments and chlorocarbon fragments. These findings establish solvent-induced catalyst modification as a useful design principle for challenging heterogeneous hydrogenations of sulfur-containing heteroarenes.