Wei-Liang Duan

The development of chiral ligands that enable efficient asymmetric C–H functionalization remains a central challenge in asymmetric catalysis. Herein, we report a new class of chiral carboxamide ligands, in combination with an achiral [Ind*IrI ₂ ] ₂ catalyst, that promotes the enantioselective C–H activation of diarylphosphine oxides with p ‐toluenesulfonyl azide. The reaction proceeds under mild conditions to afford a range of P ‐stereogenic phosphine oxides featuring sulfonamide motifs in up to 75% yield and 94% ee. The synthetic utility of this method is demonstrated by the reduction of pentavalent phosphorus products to the corresponding P(III) compounds with complete stereochemical retention.

Chiral sulfur-containing fused heterocycles are privileged scaffolds in medicinal chemistry. Expanding the catalytic repertoire for the asymmetric synthesis of bioactive sulfur heterocycles via C–H activation remains a persistent pursuit. We report herein an efficient annulation of sulfoximines with diarylacetylenes catalyzed by an achiral Cp*Rh(III) complex, where stereocontrol is governed by a chiral carboxylic amide additive. This protocol provides access to a diverse array of enantioenriched 1,2-benzothiazines in excellent yields (up to 99%) and enantioselectivities (up to 99% ee).

We report an efficient Co(II)-catalyzed asymmetric C–H annulation of arylphosphinamides with alkynes, providing streamlined access to both P-stereogenic and axially chiral arylphosphinamides. By employing modular, amino acid-derived chiral carboxylic amides as steering ligands, this catalytic manifold governs stereoselectivity with exceptional precision, delivering the target compounds in high yields (up to 99%) and enantioselectivities (up to 98% ee).

Although directed C–H activation has revolutionized organic synthesis, the asymmetric functionalization of arenes in the absence of directing groups remains a formidable challenge. Here we show that a palladium-catalyzed C–H activation reaction enables the enantioselective coupling of undirected arenes and heteroarenes with cyclopentene derivatives. Facilitated by a class of readily accessible chiral pyridone-oxazoline ligands, this protocol promotes efficient C(sp²)–H activation to generate the products featuring two stereocenters with excellent stereocontrol (up to 96% ee and 40:1 dr).

Asymmetric palladium/norbornene (NBE) cooperative catalysis is a powerful platform for assembling complex molecules. However, achieving enantiocontrol remains a fundamental challenge in cascades where the stereodetermining step occurs strictly after NBE extrusion. We report a conceptually distinct palladium-catalyzed annulation enabled by an exogenous chiral hydroxamic ester. This ligand remains coordinated to the palladium center throughout the catalytic cycle, affording diverse seven-membered P-stereogenic phosphepine oxides in moderate to good yields and up to 92% ee.

ConspectusChiral phosphines represent a cornerstone of molecular sciences, serving as the "privileged engines" that drive modern asymmetric catalysis. Despite their utility, the catalytic construction of chiral phosphorus compounds remains a formidable challenge, primarily because trivalent phosphorus nucleophiles tend to poison metal centers─a phenomenon we term the "Coordination Paradox". Our laboratory has systematically addressed this bottleneck by pioneering two distinct catalytic manifolds governed by fundamentally different chemical principles. The first strategy centers on a "Logic of Robustness" designed to thwart the deactivation pathways triggered by phosphorus nucleophiles. By engineering rigid, tridentate PCP and PCP' pincer complexes, we created a coordinatively protected environment for transition metals. This robust platform facilitated the first highly enantioselective 1,4- and 1,6-additions to diverse Michael acceptors, ultimately enabling the challenging asymmetric alkylation of primary phosphines. The second strategy pursues a logic of high atom-efficiency through direct synthesis. We introduced chiral phosphoric acids (CPAs) and carboxylic amides as stereocontrol elements in Pd- and Ir-catalyzed C-H bond activation. This approach does not merely supplement existing methods; it offers a direct route to structurally complex motifs─such as benzophosphole oxides and axially chiral biaryl phosphine. By participating in the concerted metalation-deprotonation (CMD) manifold, the CPA/amide directs the cleavage of enantiotopic C-H bonds with high fidelity. Furthermore, the development of novel nucleophiles, such as secondary phosphine sulfides and 2-pyridyl phosphine oxides, has resolved long-standing issues regarding regioselectivity and catalyst deactivation in allylic substitution and cross-coupling. Collectively, these advancements shift the field from labor-intensive stoichiometric methods toward an era of modular, atom-economical catalytic synthesis, providing a versatile toolkit for the chiral phosphorus community.

An iridium-catalyzed asymmetric allylic substitution (AAS) method was reported to produce branched allylic phosphonothioate compounds with exceptional stereocontrol (over 99% ee) and high regioselectivity under mild conditions.

A Pd-catalyzed intramolecular asymmetric double C-H activation reaction was reported, and a BINOL skeleton-based chiral phosphoric acid (CPA) was identified as a suitable ligand for this transformation. A broad range of P-stereogenic benzophosphole oxides were synthesized in moderate to excellent yield with high levels of enantioselectivity (≤96% ee).

Transition metal-catalyzed C–H bond functionalization is an important method in organic synthesis, but the development of methods that are lower cost and have a less environmental impact is desirable. Here, a Cu-catalyzed asymmetric C(sp²)–H arylation is reported. With diaryliodonium salts as arylating reagents, a range of ortho-arylated P-chiral phosphonic diamides were obtained in moderate to excellent yields with high enantioselectivities (up to 92% ee). Meanwhile, enantioselective C-3 arylation of diarylphosphine oxide indoles was also realized under similar conditions to construct axial chirality.

A Pd-catalyzed asymmetric phosphination of α,β-unsaturated sulfonyl fluorides was developed, and a series of tertiary phosphorus compounds were obtained in excellent yields and enantioselectivities (up to 99% ee). The chiral adduct can be further converted into chiral phosphine sulfonic acid as the ligand for the arene Ru metal complex.