Synthesis of α,β-unsaturated ketones through nickel-catalysed aldehyde-free hydroacylation of alkynes
Joon Ho Rhlee, Saikat Maiti, Jeong Woo Lee, Ho Seung Lee, Ismoili Ahror Bakhtiyorzoda, Soochan Lee, Jaehyun Park, Seok Ju Kang, Yung Sam Kim, Jeong Kon Seo, Kyungjae Myung, Wonyoung Choe, Sung You Hong
Abstract
α,β-Unsaturated ketones are common feedstocks for the synthesis of fine chemicals, pharmaceuticals, and natural products. Transition metal-catalysed hydroacylation reactions of alkynes using aldehydes have been recognised as an atom-economical route to access α,β-unsaturated ketones through chemoselective aldehydic C-H activation. However, the previously reported hydroacylation reactions using rhodium, cobalt, or ruthenium catalysts require chelating moiety-bearing aldehydes to prevent decarbonylation of acyl-metal-hydride complexes. Herein, we report a nickel-catalysed anti-Markovnikov selective coupling process to afford non-tethered E-enones from terminal alkynes and S-2-pyridyl thioesters in the presence of zinc metal as a reducing agent. Utilization of a readily available thioester as an acylating agent and water as a proton donor enables the mechanistically distinctive and aldehyde-free hydroacylation of terminal alkynes. This non-chelation-controlled approach features mild reaction conditions, high step economy, and excellent regio- and stereoselectivity.