Chiral N-cyclopropyl pyrazoles and structurally related heterocycles are prepared using an earth-abundant copper catalyst under mild reaction conditions with high regio-, diastereo-, and enantiocontrol. The observed N 2 :N 1 regioselectivity favors the more hindered nitrogen of the pyrazole. Experimental and DFT studies support a unique mechanism that features a five-centered aminocupration.

Experimental 13C kinetic isotope effects (KIEs) provide unprecedented mechanistic insight into three intermolecular anti-Markovnikov alkene hydrofunctionalization reactionshydroesterification, hydroamination, and hydroetherificationenabled by organophotoredox catalysis. All three reactions are found to proceed via initial oxidation of the model alkenes to form a radical cation intermediate, followed by sequential nucleophilic attack and hydrogen-atom transfer to deliver the hydrofunctionalized product. A normal 13C KIE on the olefinic carbon that undergoes nucleophilic attack provides qualitative evidence for rate-limiting nucleophilic attack in all three reactions. Comparison to predicted 13C KIE values obtained from density functional theory (DFT) calculations for this step reveals that alkene oxidation has partial rate-limiting influence in hydroesterification and hydroamination, while the nucleophilic attack is solely rate-limiting in the hydroetherification reaction. The basic additive (2,6-lutidine) activates the nucleophile via deprotonation and is an integral part of the transition state for nucleophilic attack on the radical cation, providing an important design principle for the development of asymmetric versions of these reactions. A more electron-rich pyridine base (2,6-dimethoxypyridine) exhibits considerable rate enhancements in both inter- and intramolecular hydrofunctionalization reactions.

We describe a copper catalyst that promotes the addition of phosphines to cyclopropenes at ambient temperature. A range of cyclopropylphosphines bearing different steric and electronic properties can now be accessed in high yields and enantioselectivities. Enrichment of phosphorus stereocenters is also demonstrated via a Dynamic Kinetic Asymmetric Transformation (DyKAT) process. A combined experimental and theoretical mechanistic study supports an elementary step featuring insertion of a CuI‐phosphido into a carbon‐carbon double bond. Density functional theory calculations reveal migratory insertion as the rate‐ and stereo‐determining step, followed by a syn‐protodemetalation.

Experimental 13C kinetic isotope effects (KIEs) provide unprecedented mechanistic insight into three intermolecular anti-Markovnikov alkene hydrofunctionalization reactions – hydroesterification, hydroamination, and hydroetherification – enabled by organophotoredox catalysis. All three reactions are found to proceed via initial oxidation of the model alkene (anethole) to form a radical cation intermediate followed by sequential nucleophilic attack and hydrogen-atom transfer to deliver the hydrofunctionalized product. A normal 13C KIE on the olefinic carbon that undergoes nucleophilic attack provides qualitative evidence for rate-limiting nucleophilic attack in all three reactions. Comparison to predicted 13C KIE values obtained from DFT calculations for this step reveals that alkene oxidation has partial rate-limiting influence in hydroesterification and hydroamination, while the nucleophilic attack is solely rate-limiting in the hydroetherification reaction. The basic additive (2,6-lutidine) activates the nucleophile via deprotonation and is an integral part of the transition state for nucleophilic attack on the radical cation – providing an important design principle for the development of asymmetric versions of these reactions.

We describe a copper catalyst that promotes the addition of phosphines to cyclopropenes at ambient temperature. A range of cyclopropylphosphines bearing different steric and electronic properties can now be accessed in high yields and enantioselectivities. Enrichment of phosphorus stereocenters is also demonstrated via a Dynamic Kinetic Asymmetric Transformation (DyKAT) process. A combined experimental and theoretical mechanistic study supports an elementary step featuring insertion of a CuI‐phosphido into a carbon‐carbon double bond. Density functional theory calculations reveal migratory insertion as the rate‐ and stereo‐determining step, followed by a syn‐protodemetalation.