No abstract

We report herein a visible light-mediated C−H alkylation of pyridine derivatives that proceeds by simple combination of a large variety of N-alkoxypyridinium ions with alkanes in the presence of 2 mol% of fac-Ir(ppy)3 under blue illumination. The mild reaction conditions together with the high group functional tolerance make of this process a useful synthetic platform for the construction of structurally strained heterocycles. Detailed mechanistic investigations, including Density Functional Theory (DFT) calculations and quantum yield measurement, allowed to understand factors controlling the reactivity and the selectivity of the reaction.Alkylated heteroarenes are ubiquitous chemical motifs present in pharmaceuticals, natural products, and ligand scaffolds. 1,2 While access to such molecules can be achieved with different synthetic methodologies, the oxidative cross-coupling between two C−H compounds is evidently one of the most elegant approaches as it provides a direct construction of the C−C bond in a step-and atom-economical fashion. 3 -7 For instance, the generation of an alkyl radical through a hydrogen atom transfer (HAT) event and its subsequent addition to a heteroarene ring followed by a formal hydrogen atom loss can provide a rapid and direct method for heterocycle C−H alkylation. This approach, known as the Minisci reaction, 8 -11 gained much attention during the last decade with the spectacular renaissance of the field of photoredox catalysis that provides very mild conditions for the generation of alkyl radicals. 12 -19 While various elegant photoredox Minisci reactions employing HAT strategy for the generation of the alkyl radical have been developed, there is in most cases need to use an external oxidant and stoichiometric amounts of Brønsted acids to activate the heteroarene ring towards radical addition. 20 -27 Scheme 1. (A) Reported Approaches for C−H Alkylation of Heteroarenes. (B) Current work. HAT denotes Hydrogen Atom Transfer.