Iridium-Catalyzed Intramolecular β-C–H Alkenylation of Ketones with Alkynes via a Hydride-Transfer Approach

Abstract

Direct functionalization of carbonyl β C–H bonds without using directing groups has not been a trivial task, and it is even more challenging to realize the corresponding atom-economical transformations with common alkenes or alkynes as the coupling partner. Here, we describe the development of an iridium-catalyzed intramolecular direct β-alkenylation of ketones with regular alkynes. The reaction is redox neutral, avoids strong acids or bases, and tolerates various functional groups. The combined experimental and computational mechanistic studies reveal a hydride-transfer pathway, involving ketone α,β-desaturation, iridium-hydride-mediated alkyne insertion, conjugate addition, and α-protonation.

Iridium-Catalyzed Oxidant-Free Transfer Dehydrogenation of Carboxylic Acids

“…Based on our continued interest in carbonyl desaturation and its related transformations, particularly the recent development of an Ir-catalyzed byproduct-free β-alkenylation of ketones with alkynes, 14 here we describe our preliminary development of an Ir-catalyzed transfer-dehydrogenation of carboxylic acids (Scheme 1C). It was hypothesized that the carboxylate moiety first directs oxidative addition of Ir(I) into the β or γ C−H bond, and followed by β-H elimination, the resulting Ir(III) dihydride species then undergoes a hydridetransfer process with an acceptor alkene to deliver the desired unsaturated product and to regenerate the Ir(I) catalyst.…”

Direct synthesis of alkylated 4-hydroxycoumarin derivatives via a cascade Cu-catalyzed dehydrogenation/conjugate addition sequence

“…2 Moreover, owing to the versatile reactivity of unsaturated compounds as synthetic intermediates, dehydrogenative desaturation reactions have great potential to couple a variety of reactions of unsaturated compounds, as illustrated by the recent pioneering studies. 3–7 For instance, White and co-workers developed a Pd-catalyzed dehydrogenative Diels–Alder reaction of terminal olefins to achieve complex cycloadducts; 4 a Dong's lab has realized β-C(sp 3 )–H arylation, 6 a ,6 b alkylation, 6 c and alkenylation 6 e of ketones via a Pd-catalyzed redox-cascade strategy. Recently, our lab has discovered a cascade dehydrogenation/C–H functionalization reaction to form alkenylated iso -coumarins using TEMPO as a mild oxidant (Scheme 1b).…”