Ligand assisted Co(ii) catalyzed direct C–H alkylation of aryl ketones with diverse alkyl halides

Abstract

A new cobalt(II) catalyst, [Co(η¹-fluorenyl)-(µ₂-OH)(MeOH)₂]₂, enables the direct ortho-C–H alkylation of aryl ketones with stoichiometric quantities of primary, secondary, and tertiary alkyl halides at room temperature using commercial-grade methanol. It proceeds efficiently without the need for excess alkyl halide, Grignard reagent, or transient directing imine groups. It exhibits remarkable functional-group tolerance and exceptional air- and moisture-stability. Furthermore, the protocol enables the alkylation of strained and functional group-bearing alkyl halides with high chemoselectivity. Notable advantages of this catalyst are its economic viability, scalability, and recyclability, which set it apart from other organometallic catalysts. We synthesized 72 ortho-alkylated compounds, including late-stage functionalized ones and demonstrated catalytic efficacy in direct C–H alkylation. The time-dependent ¹³C NMR and computational studies reveal an unusual fluorenyl-ring slippage, enabling facile C–H alkylation of aryl ketones. The kinetic isotopic study and HRMS analysis confirm the catalytic pathway. This effort represents a significant advancement toward sustainable and economically viable catalytic methodologies for direct C–H alkylation of aryl ketones, potentially opening up new avenues in organic synthesis and industrial applications.