Copper-Controlling Carbon-Centered Radical Reactivity for Methylenebisamide Synthesis via Ligand-to-Metal Charge-Transfer Excitation.

Tuning the reactivity of highly active radical intermediates is a serious challenge in organic synthesis. Herein, we describe an unexpected protocol involving visible-light-driven ligand-to-metal charge-transfer (LMCT) excited states of copper(II) chlorides and diether complexes to achieve chemoselectivity between distinct carbon-centered radicals and a chlorine radical. According to the "cut-and-sew" strategy, we leverage the LMCT excitation of CuCl2 and diether complexes to promote the cleavage of C(sp3)-C(sp3) and C(sp3)-O bonds of inert diethers, releasing methylene precursors that can respectively couple with primary or secondary amides to generate symmetrical and unsymmetrical methylenebisamide products. Mechanistic investigations have established that the methylene is furnished via the cleavage of C(sp3)-C(sp3) bonds in ethers to form amide-methylene intermediates, which subsequently undergo C(sp3)-O bond cleavage and incorporate another amide to form the desired products. Noticeably, the methylene donors were generalized to different unstrained cyclic ethers and acyclic ethers, including 18-crown-6, 15-crown-5, benzo-15-crown-5, 1,3-dioxolane, 1,4-dioxane, diglyme, 1,2-dimethoxyethane, ethylene glycol diethyl ether, BnOCH2CH2OBn, MeOCH2CH2OH, and ethylene glycol. Moreover, this reactivity profile involving LMCT excited states could be differentiated from known C(sp3)-N bond-forming reactions with two-electron manifolds.