Intermolecular selective carboacylation of alkenes via nickel-catalyzed reductive radical relay

Abstract

The development of catalytic carboacylation of simple olefins, which would enable the rapid construction of ketones with high levels of complexity and diversity, is very challenging. To date, the vast majority of alkene carboacylation reactions are typically restricted to single- and two-component methodologies. Here we describe a three-component carboacylation of alkenes via the merger of radical chemistry with nickel catalysis. This reaction manifold utilizes a radical relay strategy involving radical addition to an alkene followed by alkyl radical capture by an acyl-nickel complex to forge two vicinal C−C bonds under mild conditions. Excellent chemoselectivity and regioselectivity have been achieved by utilizing a pendant weakly chelating group. This versatile protocol allows for facile access to a wide range of important β-fluoroalkyl ketones from simple starting materials.

Nickel‐CatalyzedDicarbofunctionalization of Alkenes†

“…nickel‐catalyzed perfluoroalkyl‐acylation of simple alkenes with acyl chlorides and fluoroalkyl iodides, enabling the rapid construction of β‐fluoroalkyl ketones (Scheme 12). [ 66 ] A tethered, weakly chelating group on the alkenes was used to promote the reaction and control the chemo‐ and regio‐selectivity. A radical tandem process involving a radical addition to the alkene, followed by alkyl radical trapping with an acyl‐nickel complex was proposed.…”

Recent developments in nickel-catalyzed intermolecular dicarbofunctionalization of alkenes

“…13A). 34 Key to the success of this reaction was the careful positioning of a coordinating group in the substrate to allow for the generation of a stabilized 6-membered nickelacycle upon radical recombination. A series of mechanistic studies including substrate modication and TEMPO experiments support the directing group effect and radical addition pathway, respectively.…”

Nickel-Catalyzed Three-Component Olefin Reductive Dicarbofunctionalization to Access Highly Functionalized Alkylborates

“…4 Chu and co-workers reported an example of intermolecular olefin reductive carboacylation with fluoroalkyl iodides and acyl chlorides. 5 However, the development of important dialkylation processes 6 is relatively limited and still relies on organometallics that are sensitive to many functional groups. 7,8 Recently, dicarbofunctionalization of commercially available vinyl boronates has been applied to the diversified synthesis of alkylborates.…”