Jing Ke

Despite recent proof-of-concept advances, aromatic carbon-to-nitrogen replacement reactions remain substrate specific and exhibit an overreliance on harsh oxidation methods that preclude their deployment in demanding contexts. Transformations relying on singlet nitrene valence isomerization, in particular, have suffered from competitive intersystem crossing to the triplet spin state, which does not undergo the same rearrangement. In this work, we report a reaction that productively engages triplet aryl nitrenes for carbon-to-nitrogen replacement on the benzenoid ring of a range of bicyclic heteroarenes, including naphthalenes, anthracene, indoles, benzofurans, benzothiophene, indazoles, and benzisothiazoles. The reaction proceeds under mild conditions, which enables its application to complex, sensitive natural products.

Despite significant proof-of-concept advances, aromatic C-to-N replacement reactions remain limitingly substrate-specific and exhibit an overreliance on harsh oxidation methods that preclude their deployment in demanding contexts. Transformations relying on singlet nitrene valence insertion, in particular, have suffered from parasitic intersystem crossing to the triplet spin state, which does not undergo the same rearrangement. We report herein a reaction that productively engages triplet aryl nitrenes for C-to-N replacement with broad scope under mild conditions, enabling its application to complex, sensitive natural products.

α-Alkynyldiazomethanes, generated in situ from the corresponding sulfonyl hydrazones in the presence of a base, can serve as effective metalloradicophiles in Co(II)-based metalloradical catalysis (MRC) for asymmetric cyclopropanation of alkenes. With D₂-symmetric chiral amidoporphyrin 2,6-DiMeO-QingPhyrin as the optimal supporting ligand, the Co(II)-based metalloradical system can efficiently activate different α-alkynyldiazomethanes at room temperature for highly asymmetric cyclopropanation of a broad range of alkenes. This catalytic radical process provides a general synthetic tool for stereoselective construction of alkynyl cyclopropanes in high yields with high both diastereoselectivity and enantioselectivity. Combined computational and experimental studies offer several lines of evidence in support of the underlying stepwise radical mechanism for the Co(II)-catalyzed olefin cyclopropanation involving a unique α-metalloradical intermediate that is associated with two resonance forms of α-Co(III)-propargyl radical and γ-Co(III)-allenyl radical. The resulting enantioenriched alkynyl cyclopropanes, as showcased with several stereospecific transformations, may serve as valuable chiral building blocks for stereoselective organic synthesis.

A highly efficient catalytic method has been developed for asymmetric radical cyclopropanation of alkenes with in situ-generated α-heteroaryldiazomethanes via Co(II)-based metalloradical catalysis (MRC). Through fine-tuning the cavity-like environments of newly-synthesized D₂-symmetric chiral amidoporphyrins as the supporting ligand, the optimized Co(II)-based metalloradical system is broadly applicable to α-pyridyl and other α-heteroaryldiazomethanes for asymmetric cyclopropanation of wide-ranging alkenes, including several types of challenging substrates. This new catalytic methodology provides a general access to valuable chiral heteroaryl cyclopropanes in high yields with excellent both diastereoselectivities and enantioselectivities. Combined computational and experimental studies further support the underlying stepwise radical mechanism of the Co(II)-based olefin cyclopropanation involving α- and γ-metalloalkyl radicals as the key intermediates.