Copper/BINOL-Catalyzed Enantioselective C–H Functionalization toward Planar Chiral Ferrocenes Under Mild Conditions

Abstract

Copper-catalyzed enantioselective C−H activation proceeding through an inner-sphere mechanism remains a huge challenge. Herein, a copper-catalyzed enantioselective C−H alkynylation with terminal alkynes assisted by 8-aminoquinoline using readily available (S)-BINOL as the chiral ligand was disclosed. The reaction proceeded under mild conditions with a catalytic amount of copper salt, providing a range of chiral ferrocenes in good yields and enantioselectivities (0 °C, up to 77% yield and 94% ee). The alteration of the stoichiometric chemical oxidant with renewable electricity is also feasible at ambient temperature, demonstrating the robustness of this copper/BINOL catalysis. Notably, this is the first enantioselective cupraelectrocatalyzed C−H activation reaction. Gram-scale synthesis, versatile transformations, and application of the resulting oxazoline−olefin ligand in asymmetric synthesis also highlight the utility of the protocols.

Electrochemical Enantioselective C–H Annulation by Achiral Rhodium(III)/Chiral Brønsted Base Domino Catalysis

“…Organic electrosynthesis considerably improves the sustainability of molecular synthesis by utilizing electricity as an eco-friendly alternative to stoichiometric amounts of redox reagents, with the potential to contribute to a green hydrogen economy. − Electrochemical transition-metal-catalyzed enantioselective C–H functionalization has been identified as a versatile platform for the construction of chiral molecules. − These electrochemical pathways commonly rely on the interaction of a unique chiral catalyst with the substrates. − In sharp contrast, electrochemical cooperative catalysis, − namely two catalysts working in concert through two distinct catalytic cycles, continues to be underdeveloped.…”

“… 38 − 44 Electrochemical transition-metal-catalyzed enantioselective C–H functionalization has been identified as a versatile platform for the construction of chiral molecules. 45 − 58 These electrochemical pathways commonly rely on the interaction of a unique chiral catalyst with the substrates. 45 − 55 In sharp contrast, electrochemical cooperative catalysis, 56 − 59 namely two catalysts working in concert through two distinct catalytic cycles, continues to be underdeveloped.…”

“… 45 − 58 These electrochemical pathways commonly rely on the interaction of a unique chiral catalyst with the substrates. 45 − 55 In sharp contrast, electrochemical cooperative catalysis, 56 − 59 namely two catalysts working in concert through two distinct catalytic cycles, continues to be underdeveloped.…”

Regiodivergent Metal-Catalyzed Oxidative Alkynylation of 2-Arylthiazoles with Terminal Alkynes under Air Conditions

“…Despite this type of cross-coupling is more challenging mainly because of the sequential dual C–H activation, remarkable progress has been made on the oxidative C–H alkynylation of arenes/heteroarenes via directed strategies or nondirected strategies . With respect to the metal-catalyzed N -directed oxidative alkynylation of arenes/heteroarenes, the strategy using ruthenium as catalyst still remains unexplored probably due to the formation of alkenylated products .…”