Pharmaceutical and agrochemical companies have a longstanding interest in rapidly diversifying small molecules. Currently, the Minisci reaction is a frequently employed transformation for readily alkylating heterocycles, although inherent limitations remain: (1) use of superstoichiometric amounts of radical precursor, (2) poor regioselectivity, and (3) harsh reaction conditions. Described herein a photoredox-mediated C–H alkylation is described that address previous limitations. Using an organophotocatalyst and mild oxidant, a wide array of primary, secondary, and tertiary alkyltrifluoroborates are incorporated as latent radicals. To demonstrate the synthetic utility for late-stage functionalization, complex heteroarenes were alkylated under the unified conditions. Furthermore, a library of 2-heteroarylchromanones were accessed via 2-trifluoroboratochromanones highlighting the exceptional functional group tolerance in both radical and heteroarene partners. Mechanistic studies are also discussed to explain the enhanced regioselectivity unique to alkyltrifluoroborates.

Photoredox catalyzed CH alkylation of heteroarenes: A mild approach for late stage functionalization

254th National Meeting (2017)

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