Arene‐Ligand‐Free Ruthenium(II/III) Manifold for meta‐C−H Alkylation: Remote Purine Diversification

Abstract

meta-Selective C-H alkylations of bioactive purine derivatives were accomplished by versatile ruthenium catalysis. Thus, the arene-ligand-free complex [Ru(OAc) (PPh ) ] enabled remote C-H functionalizations with ample scope and excellent levels of chemo- and positional selectivities. Detailed experimental and computational mechanistic studies provided strong support for a facile C-H activation within a ruthenium(II/III) manifold.

meta‐Selective C−H Activation of Arenes at Room Temperature Using Visible Light: Dual‐Function Ruthenium Catalysis

“…Blue-light irradiation of the in situ formed Ru II cyclometalated complex B generates al ong-lived excited state of the Ru II complex C,w hich can undergo SET to the alkyl halide (X = Br or I) and form aC -centered radical and the Ru III -cyclometalated complex D.I nt he next step,t he nucleophilic carbon-centered alkyl radical then undergoes ar adical attack on para position to electrophilic D to afford the complex E.Recent computational work from Ackermann and co-workers has implicated Ru III as having substantially higher selectivity in this step than Ru II ,i nl ine with the proposed electron-transfer step from Ru II to alkyl halide. [13] A final LMCT step is then required to regenerate the Ru II complex F which can lose ap roton to rearomatize and deliver the desired meta-CÀHa ctivation product 3a through protonolysis.…”

Visible‐Light‐Enabled Ruthenium‐Catalyzed meta‐C−H Alkylation at Room Temperature

“…[1] Thus far, chelation assistance by directing groups has been identified as av ersatile tool for site-selective CÀHmetalations. [9][10][11][12][13] Despite indisputable progress,t he s-activation approach is limited to elevated reaction temperatures,w hich resulted in signifi-cantly reduced yields and low functional group tolerance. [3] Exploiting the substratesi nherent substitution pattern has proven useful, but this approach still largely suffers from limited substrate scope.…”

“…As au niquely versatile alternative, meta-C À Hf unctionalizations through arene s-activation [8] were realized by chelation-assisted ortho-cycloruthenation. [9][10][11][12][13] Despite indisputable progress,t he s-activation approach is limited to elevated reaction temperatures,w hich resulted in signifi-cantly reduced yields and low functional group tolerance. Conversely,r oom-temperature metal-catalyzed meta-CÀH functionalization has thus far unfortunately proven elusive.…”

Towards Sustainable C−H Functionalization Reactions: The Emerging Role of Bio‐Based Reaction Media

“…Indeed, more challenging meta-selective [42] CÀHf unctionalizations provedr ecently viable within an arene-ligand-free ruthenium(II/III) manifold (Scheme 14). [43] The site-selective ruthenium catalyst enabled organometallic CÀHa ctivation through cycloruthenation, setting the stage for remote purine [44] base diversification. The reaction could be efficientlyc onducted also in other solvents, with 1,4-dioxane and tolueneg iving comparable results to 2-MeTHF.…”