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.
Highlights
Α,β-Unsaturated ketones are common feedstocks for the synthesis of fine chemicals, pharmaceuticals, and natural products
The catalytic hydroacylation of alkynes using aldehydes inherently provides an atom-economical process leading to the formation of enones
Though nondirected hydroacylation methods have been developed for alkenes or dienes[32,33,34,35,36], to our knowledge, there is no general hydroacylation method for unactivated terminal alkynes that lead to chelating moiety-free Eenones
Summary
Α,β-Unsaturated ketones are common feedstocks for the synthesis of fine chemicals, pharmaceuticals, and natural products. The catalytic hydroacylation of alkynes using aldehydes inherently provides an atom-economical process leading to the formation of enones. A consecutive alkyne insertion and subsequent protodemetalation process may lead to hydroacylation product formation (Fig. 1c). We report a nondirected and aldehyde-free approach to afford E-enones via a nickel-catalyzed reductive pathway.
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