Palladium‐Catalyzed Decarboxylative Alkynylation of α‐Acyloxyketones by C(sp³)−O Bond Cleavage

Abstract

Palladium‐catalyzed decarboxylative alkynylation of α‐acyloxyketones triggered by C(sp3)−O bond cleavage is disclosed. The decarboxylation strategy featuring a neutral reaction condition enabled an unprecedent catalytic alkynylation of a ketone enolate. The reaction was applied to a variety of substrates, giving desired products in good yields. We successfully obtained X‐ray crystallography of a new palladium–enolate intermediate that was synthesized by a reaction of [Pd(cod)(CH2TMS)2] with XPhos and α‐acyloxyketone at room temperature, indicating facile C(sp3)−O bond disconnection.

Unimolecular Fragment Coupling: A New Bond-Forming Methodology via the Deletion of Atom(s)

“…Examples of decarboxylative UFC using esters other than allylic or benzylic systems are currently limited because catalysts that can activate nonallylic C–O bonds in preference to normally more reactive C­(acyl)–O bonds are less explored. Doi, Sato and co-workers reported a palladium-catalyzed decarboxylative UFC of α-acyloxyketones bearing an alkyne moiety, which is triggered by the activation of a C­(sp 3 )–O bond α to a carbonyl group (Scheme , top) . The key to success is the coordination of the Pd(0) complex to a ketone, which facilitates the activation of a C­(sp 3 )–O bond at the α-position to form a Pd enolate intermediate.…”

“…Doi, Sato and co-workers reported a palladium-catalyzed decarboxylative UFC of α-acyloxyketones bearing an alkyne moiety, which is triggered by the activation of a C(sp 3 )–O bond α to a carbonyl group ( Scheme 7 , top). 47 The key to success is the coordination of the Pd(0) complex to a ketone, which facilitates the activation of a C(sp 3 )–O bond at the α-position to form a Pd enolate intermediate. While alkynylation at the α-position of ketones by cross-coupling reactions often suffers from the undesired dimerization of alkynes, such byproducts can be avoided in this decarboxylative UFC.…”