Copper-Catalyzed Desaturation of Lactones, Lactams, and Ketones under pH-Neutral Conditions

A copper-catalyzed
desaturation method that is suitable for converting
lactones, lactams, and cyclic ketones to their α,β-unsaturated
counterparts is reported. The reaction does not require strong base/acid
or sulfur/selenium reagents and can be carried out through a simple
one-step operation. The protocol uses inexpensive catalysts and reagents
and exhibits excellent scalability and functional group tolerance.
Notably, tert-butyl alcohol is the only stoichiometric
byproduct produced, and overoxidation is not observed. The reaction
mechanism has been investigated through control experiments, deuterium
labeling, radical clock, electron paramagnetic resonance, high-resolution
mass spectrometry, and kinetic studies. The data obtained are consistent
with a reaction pathway involving reversible α-deprotonation
by a Cu­(II)–OtBu species followed
by further oxidation of the resulting Cu enolate.