Synthesis of Primary Thioamides by the Insertion of CS2 into Aldoximes
Marcos López-Aguilar1, Nicolás Ríos-Lombardía1, Daniel Barrena-Espés2
1Laboratorio de Química Sintética Sostenible (QuimSinSos), Organic and Inorganic Chemistry Department, Instituto de Química Organometálica Enrique Moles, Universidad de Oviedo, Avenida Julián Clavería 8, 33006 Oviedo, Asturias, Spain.
Abstract:
Aldoximes react with CS2 in the presence of DBU and TBACl, providing access to primary thioamides. This unprecedented reaction proceeds under metal-free and mild conditions and tolerates a broad range of substrates. Its robustness has been demonstrated on the synthesis of active drug Febuxostat (gout) and an advanced intermediate in the synthesis of SRT2104 (type 2 diabetes). Computational studies, based on DFT calculations, have revealed the roles of both the base and TBACl in the reaction and have elucidated the reaction mechanism, which differs significantly from those displayed for other CS2 insertions.
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