Olefination via Cu-Mediated Dehydroacylation of Unstrained Ketones

Abstract

The dehydroacylation of ketones to olefins is realized under mild conditions, which exhibits a unique reaction pathway involving aromatization-driven C-C cleavage to remove the acyl moiety, followed by Cu-mediated oxidative elimination to form an alkene between the α and β carbons. The newly adopted N'-methylpicolinohydrazonamide (MPHA) reagent is key to enable efficient cleavage of ketone C-C bonds at room temperature. Diverse alkyl- and aryl-substituted olefins, dienes, and special alkenes are generated with broad functional group tolerance. Strategic applications of this method are also demonstrated.

Figure 1.

Synthetic potential and reaction design of the dehydroacylation of ketones.

Scheme 1.

Aromatization-Driven Ketone C–C Cleavage

Scheme 2.. Reaction Optimization

^aThe yields are based on ¹H NMR analysis of the crude reaction mixture. ^bIsolated yield.

Scheme 3.. Substrate Scope^a,b

^aUnless otherwise mentioned, all reactions were conducted on a 0.2 mmol scale. ^bIsolated yields. ^c0.4 mmol scale. ^d0.5 mmol scale. ^e0.1 mmol scale. ^fDMSO instead of DMSO:H₂O (4:1). ^gThe E/Z ratio was determined by ¹H NMR analysis. brsm, (yield) based on recovered starting material.

Scheme 4.. Further Applications^a,b

^a Unless otherwise mentioned, all reactions were conducted on a 0.2 mmol scale. ^bIsolated yields. ^c0.1 mmol scale. ^d0.4 mmol scale. ^e0.5 mmol scale. ^f2.0 mmol scale. ^gThe E/Z ratio was determined by ¹H NMR analysis. For detailed experimental procedures, see the Supporting Information.