Tailored cobalt-salen complexes enable electrocatalytic intramolecular allylic C–H functionalizations

Abstract

Oxidative allylic C–H functionalization is a powerful tool to streamline organic synthesis as it minimizes the need for functional group activation and generates alkenyl-substituted products amenable to further chemical modifications. The intramolecular variants can be used to construct functionalized ring structures but remain limited in scope and by their frequent requirement for noble metal catalysts and stoichiometric chemical oxidants. Here we report an oxidant-free, electrocatalytic approach to achieve intramolecular oxidative allylic C–H amination and alkylation by employing tailored cobalt-salen complexes as catalysts. These reactions proceed through a radical mechanism and display broad tolerance of functional groups and alkene substitution patterns, allowing efficient coupling of di-, tri- and even tetrasubstituted alkenes with N- and C-nucleophiles to furnish high-value heterocyclic and carbocyclic structures.

Progress in the Electrochemical Reactions of Sulfonyl Compounds

“…Alkenes are versatile building blocks in modern organic synthesis [34] . It has been reported that alkenes could be attacked by electrogenerated thiophenol radicals, [35] alcohol radicals, [9d,36] and nitrogen radicals [9a,37] . In this chapter, we demonstrate the reactions involving sulfonyl compounds as radical precursors and alkenes as radical acceptors.…”

Electrocatalytic Allylic C−H Alkylation Enabled by a Dual‐Function Cobalt Catalyst**

“…Building on our previous studies on intramolecular allylic C−H functionalizations, [39] we surmise that the acidic carbon nucleophile can be oxidized electrocatalytically with a cobalt‐based molecular catalyst to generate an electron‐deficient carbon‐centered radical, [39–41] which then adds to the alkene to afford an alkyl radical. The newly formed radical center significantly weakens the γ‐C−H bond [bond dissociation energy (BDE) <36 kcal mol −1 ], [42] enabling effective hydrogen atom transfer (HAT) to the cobalt catalyst to furnish the alkene alkylation product [39, 43] . In contrast to the organometallic C−H activation, the presence of substituents at the β‐ or γ‐positions of the alkene substrate should not interfere with the radical reactions; in fact, they might even be beneficial, thus expanding the substrate scope to branched alkenes.…”

“…While the voltammogram exhibited no change with the addition of 2 and Na 2 CO 3 , the reduction wave for [Co III ]/[Co II ] disappeared in the presence of 2 and NaOMe but without the observation of a catalytic current [50] . These results suggested that the electrochemically produced [Co III ] species reacted with the conjugate base of 2 through inner‐sphere electron transfer [39] . Na 2 CO 3 was barely soluble in the mixed solvent of DMF/MeCN (1 : 1), explaining its failure in promoting the reaction of [Co III ] with 2 under the static conditions employed for the CV testing.…”

“…The success of the electrocatalytic reaction hinges on the dual function of the cobalt catalyst as a redox mediator and a site-selective HAT catalyst. Our previous work has shown that cobalt-salen complexes are competent electrocatalysts for promoting intramolecular cyclizations, [39] paving the way for the more challenging intermolecular allylic CÀ H alkylation reactions.…”

The Renaissance of Electro‐Organic Synthesis for the Difunctionalization of Alkenes and Alkynes: A Sustainable Approach

“…It was seen that the redox catalyst played a vital role in the electrochemical transformation (Scheme 70). [129] A series of starting materials were employed for the reaction and gram scale synthesis of the desired product was achieved. The reaction proceeded via anodic oxidation of tris(2,4‐dibromophenyl)amine to generate the radical cation which catalyzes the oxidation of olefin through SET to form the radical cation.…”