Herein, we report an achiral dirhodium complex and chiral phosphoric acid cooperatively catalyzed asymmetric threecomponent reaction of enynal with alcohol and imine, affording chiral α-furyl-β-amino carboxylates in good to high yields with generally excellent stereoselectivity. The successful introduction of enynal as a carbene precursor in this reaction provides an expeditious track to prepare complex furan derivatives with adjacent quaternary and tertiary stereocenters. The starting materials are stable and readily available, and the method features 100% atom economy with high bond-formation efficiency. This is a highly enantioselective gem-difunctionalization reaction of metal carbene generated in situ from enynal. These generated chiral products could be smoothly converted to polycyclic frameworks and drug-conjugated derivatives through different cycloaddition reactions.

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N-(Anthrancen-9-ylmethyl) isoserines are useful drug intermediates but short for efficient synthesis. We herein report the synthesis of N-(anthrancen-9-ylmethyl) isoserines via a Rh2(Ph3COO)3(OAc) and chiral phosphoric acid (CPA) synergistically catalyzed multicomponent reaction (MCR) of N-alkyl imines, alcohols, and diazoesters. The method representing the first example of N-alkyl imines-involved MCR is featured by high atom-economy, high diastereo- and enantioselectivities, and broad substrate scope. DFT calculations on the mechanism of the MCR reveals that the hydrophobic interactions and π–π stackings between N-(anthrancen-9-ylmethyl) imines and Rh2(Ph3COO)3(OAc)/CPA cocatalyst is essential to the reactivity and stereocontrol. The synthetic applications of the MCR products include the semisynthesis of paclitaxel, its alkyne-tagged derivative, and β-lactam as an anticancer agent overcoming paclitaxel-resistance. We expect this work to shed light on the development of new N-alkyl imines-involved reactions and on the synthesis of drugs with isoserines as intermediates.

Metallaphotocatalysis has been recognized as a pivotal catalysis for enabling new reactivities and for expanding chemical space. Traditional metallaphotocatalysis often requires two or more separate catalysts and exhibits flaw in cost and substrate-tolerance, thus representing an await-to-solve issue in catalysis. We herein realize metallaphotocatalysis with a bifunctional dirhodium tetracarboxylate ([Rh2]) alone.The [Rh2] shows an unprecedente photocatalytic activity via a rarely used metal-to-metal transition in photocatalysis. Based on the activity, the [Rh2] connects carbene chemistry and siglet oxygen chemistry to enable a novel photochemical cascde reaction (PCR). The PCR is characterized by high atom-efficiency, excellent stereoselectivities, mild conditions, scalable synthesis, and valuable products. DFT calculations-aided mechanistic study rationalizes the reaction pathway and interprets stereoselectivities of the PCR. The products showed inhibitory activity against PTP1B, being promising in the treatment of type II diabetes and cancers. We believe this work will shed light on discovering bifunctional catalysts for metallaphotocatalysis and on developing PCRs for exploring chemical space.