Chiral Metal Catalysts Research Articles

Ligand-Enabled Cu-Catalyzed Stereoselective Synthesis of P-Stereogenic ProTides.

Nucleoside analogues have seen significant advancements in treating viral infections and cancer through ProTide technology, leading to a series of FDA-approved drugs such as sofosbuvir, tenofovir alafenamide, and remdesivir. The stereochemical configuration at the phosphorus center of ProTides significantly influences their pharmacological properties, necessitating efficient stereoselective synthesis. Traditional methods using chiral auxiliaries or nonracemic phosphorylating agents are labor-intensive and inefficient, while recent organocatalytic approaches, despite their promise, still face limitations. Herein, we present a novel approach employing chiral metal complexes for the stereoselective assembly of P-stereogenic ProTides via asymmetric P-O bond formation. This approach leverages a chiral metal catalyst to activate the electrophilic phosphorylating reagent, facilitating a base-promoted nucleophilic replacement pathway. Our protocol, featuring mild reaction conditions and broad applicability, enables the highly stereoselective synthesis of previously inaccessible (S,RP) and (R,SP)-ProTide derivatives. The practical utility of this method is demonstrated through the preparation of pharmaceutically relevant ProTide targets and mechanistic studies were conducted to elucidate the reaction pathway, offering significant advancements for drug development and pharmaceutical research.

Stereodivergent Construction of 1,5/1,7-Nonadjacent Tetrasubstituted Stereocenters Enabled by Pd/Cu-Cocatalyzed Asymmetric Heck Cascade Reaction.

The construction of chiral motifs containing nonadjacent stereocenters in an enantio- and diastereoselective manner has long been a challenging task in synthetic chemistry, especially with respect to their stereodivergent synthesis. Herein, we describe a protocol that enables the enantio- and diastereoselective construction of 1,5/1,7-nonadjacent tetrasubstituted stereocenters through a Pd/Cu-cocatalyzed Heck cascade reaction. Notably, a C=C bond relay strategy involving the shift of the π-allyl palladium intermediate was successfully applied in the asymmetric construction of 1,7-nonadjacent stereocenters. The current method allows for the efficient preparation of chiral molecules bearing two privileged scaffolds, oxindoles and non-natural α-amino acids, with good functional group tolerance. The full complement of the four stereoisomers of products bearing 1,5/1,7-nonadjacent stereocenters could be readily accessed by a simple combination of two chiral metal catalysts with different enantiomers.

Stereodivergent Construction of 1,5/1,7‐Nonadjacent Tetrasubstituted Stereocenters Enabled by Pd/Cu‐Cocatalyzed Asymmetric Heck Cascade Reaction

AbstractThe construction of chiral motifs containing nonadjacent stereocenters in an enantio‐ and diastereoselective manner has long been a challenging task in synthetic chemistry, especially with respect to their stereodivergent synthesis. Herein, we describe a protocol that enables the enantio‐ and diastereoselective construction of 1,5/1,7‐nonadjacent tetrasubstituted stereocenters through a Pd/Cu‐cocatalyzed Heck cascade reaction. Notably, a C=C bond relay strategy involving the shift of the π‐allyl palladium intermediate was successfully applied in the asymmetric construction of 1,7‐nonadjacent stereocenters. The current method allows for the efficient preparation of chiral molecules bearing two privileged scaffolds, oxindoles and non‐natural α‐amino acids, with good functional group tolerance. The full complement of the four stereoisomers of products bearing 1,5/1,7‐nonadjacent stereocenters could be readily accessed by a simple combination of two chiral metal catalysts with different enantiomers.

Photochemical Synthesis of Chiral Heterocycles via Asymmetric Carbon‐Heteroatom Bond Formation

AbstractChiral heterocyclic compounds play a crucial role in the pharmaceutical science, materials science, and agrochemical industries. The critical step for synthesizing chiral heterocycles is the formation of asymmetric carbon‐heteroatom bonds, which can be achieved in a chiral environment under thermal or photochemical conditions. However, photochemical asymmetric transformation has become an area of immense growth in the past 15 years. In the drug discovery and development era, chiral photochemical transformations have drawn the attention of researchers to develop new synthetic strategies for chiral heterocycles via asymmetric carbon‐heteroatom bond formation. Chiral photochemistry in the pathway of asymmetric synthesis requires a chirality source which is transferred to the products. A catalytic chiral metal complexing agent or a chiral photosensitizer that generally follows a single electron transfer (SET) or oxidative and reductive quenching cycle has been widely exploited to achieve this goal. In this review, we have demonstrated the recent development of photochemical synthesis of chiral heterocycles via asymmetric carbon‐heteroatom bond formation by using a chiral metal catalyst, asymmetric organocatalyst, or dual catalytic system based on their plausible mechanism.

Iridium-Catalyzed Asymmetric Hydrogenation of Heteroaromatics with Multiple N Atoms via Substrate Activation: An Entry to 4,5,6,7-Tetrahydropyrazolo[1,5-a]pyrimidine-3-carbonitrile Core of a Potent BTK Inhibitor.

The chiral 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine is the key core skeleton of potent Bruton's tyrosine kinase (BTK) inhibitor Zanubrutinib, and the catalyst-controlled asymmetric hydrogenation of planar multinuclear pyrimidine heteroarenes with multiple N atoms could provide an efficient route toward its synthesis. Owing to the strong aromaticity and poisoning effect toward chiral transition metal catalyst, asymmetric hydrogenation of pyrazolo[1,5-a]pyrimidines with multiple nitrogen atoms is still a challenge for synthesizing the chiral 4,5,6,7-tetrahydropyrazolo[1,5-a]-pyrimidine. Herein, an efficient iridium-catalyzed asymmetric hydrogenation of pyrazolo[1,5-a]pyrimidines has been developed using substrate activation strategy, with up to 99% ee. The decagram scale synthesis further demonstrated the potential and promise of this procedure in the synthesis of Zanubrutinib. In addition, a mechanistic study indicated that the hydrogenation starts with 1,2-hydrogenation.

Catalytic asymmetric carbenoid α-C-H insertion of ether.

Significant advancements have been made in catalytic asymmetric α-C-H bond functionalization of ethers via carbenoid insertion over the past decade. Effective asymmetric catalytic systems, featuring a range of chiral metal catalysts, have been established for the enantioselective synthesis of diverse ether substrates. This has led to the generation of various enantioenriched, highly functionalized oxygen-containing structural motifs, facilitating their application in the asymmetric synthesis of bioactive natural products.

Chiral-at-Ruthenium Catalysts for Nitrene-Mediated Asymmetric C–H Functionalizations

ConspectusAsymmetric transition metal catalysis is an indispensable tool used both in academia and industry for forging chiral molecules in an enantioselective fashion. Its advancement relies in large part on the design and discovery of new chiral catalysts. In contrast to conventional endeavors of generating chiral transition metal catalysts from carefully tailored chiral ligands, the development of chiral transition metal catalysts containing solely achiral ligands (chiral-at-metal catalysts) has been neglected. This Account presents our recent work on the synthesis and catalytic applications of a new class of C2-symmetric chiral-at-ruthenium catalysts. These octahedral ruthenium(II) complexes are constructed from two achiral bidentate N-(2-pyridyl)-substituted N-heterocyclic carbene (PyNHC) ligands and two monodentate acetonitriles, and the dicationic complexes are typically complemented with two hexafluorophosphate anions. The chirality of these complexes originates from the helical cis-arrangement of the bidentate ligands, thereby generating a stereogenic metal center as the exclusive stereocenter in these complexes. The strong σ donor and π acceptor properties of the PyNHC ligands provide a strong ligand field that ensures a high constitutional and configurational inertness of the helical Ru(PyNHC)2 core, while at the same time, the trans-effect exerted by the σ-donating NHC ligands results in high lability of the MeCN ligands and, therefore, provides high catalytic activity. As a result, this chiral-at-ruthenium catalyst scaffold combines formidable structural robustness with high catalytic activity in a unique fashion. Asymmetric nitrene C-H insertion constitutes an efficient strategy for accessing chiral amines. The direct conversion of C(sp3)-H bonds into amine functionality circumvents the need for using functionalized starting materials. Our C2-symmetric chiral-at-ruthenium complexes display exceptionally high catalytic activity and excellent stereocontrol for various asymmetric nitrene C(sp3)-H insertion reactions. The ruthenium nitrene species can be generated from nitrene precursors, such as organic azides and hydroxylamine derivatives, which undergo ring-closing C-H aminations to afford chiral cyclic pyrrolidines, ureas, and carbamates in high yields and with excellent enantioselectivities at low catalyst loadings. Mechanistically, the turnover-determining C-H insertion is proposed to proceed in a concerted or stepwise fashion, depending on the nature of intermediate ruthenium nitrenes (singlet or triplet). Computational studies revealed that the stereocontrol originates from a better steric fit in combination with favorable catalyst/substrate π-π stacking effects for aminations at benzylic C-H bonds. In addition, we also present our research for exploring novel reaction patterns and reactivities of intermediate transition metal nitrenes. First, we discovered a novel chiral-at-ruthenium-catalyzed 1,3-migratory nitrene C(sp3)-H insertion to convert azanyl esters into nonracemic α-amino acids. Second, we found a chiral-at-ruthenium-catalyzed intramolecular C(sp3)-H oxygenation, thereby allowing for the construction of chiral cyclic carbonates and lactones via nitrene chemistry. We expect that our research program on catalyst development and reaction discovery will inspire the creation of novel types of chiral-at-metal catalysts and drive the development of new applications for nitrene-mediated asymmetric C-H functionalization reactions.

Metal Stereogenicity in Asymmetric Transition Metal Catalysis.

Chiral transition metal catalysts represent a powerful and economic tool for implementing stereocenters in organic synthesis, with the metal center providing a strong chemical activation upon its interaction with substrates or reagents, while the overall chirality of the metal complex achieves the desired stereoselectivity. Often, the overall chiral topology of the metal complex implements a stereogenic metal center, which is then involved in the origin of the asymmetric induction. This review provides a comprehensive survey of reported chiral transition metal catalysts in which the metal formally constitutes a stereocenter. A stereogenic metal center goes along with an overall chiral topology of the metal complex, regardless of whether the ligands are chiral or achiral. Implications for the catalyst design and mechanism of asymmetric induction are discussed for half-sandwich, tetracoordinated, pentacoordinated, and hexacoordinated chiral transition metal complexes containing a stereogenic metal center. The review distinguishes between chiral metal catalysts originating from the coordination to chiral ligands and those which are solely composed of optically inactive ligands (achiral or rapidly interconverting enantiomers) prior to complexation (dubbed "chiral-at-metal" catalysts).

Stereodivergent Synthesis of Allenes with α,β‐Adjacent Central Chiralities Empowered by Synergistic Pd/Cu Catalysis

AbstractThe stereodivergent synthesis of allene compounds bearing α,β‐adjacent central chiralities has been realized via the Pd/Cu‐catalyzed dynamic kinetic asymmetric alkylation of racemic allenylic esters. The matched reactivity of bimetallic catalytic system enables the challenging reaction of racemic aryl‐substituted allenylic acetates with sterically crowded aldimine esters smoothly under mild reaction conditions. Various chiral non‐natural amino acids bearing a terminal allenyl group are easily synthesized in high yields and with excellent diastereo‐ and enantioselectivities (up to >20 : 1 dr, >99 % ee). Importantly, all four stereoisomers of the product can be readily accessed by switching the configurations of the two chiral metal catalysts. Furthermore, the easy interconversion between the uncommonη3‐butadienyl palladium intermediate featuring a weak C=C/Pd coordination bond and a stable Csp2−Pd bond is beneficial for the dynamic kinetic asymmetric transformation process (DyKAT).

Stereodivergent Synthesis of Allenes with α,β-Adjacent Central Chiralities Empowered by Synergistic Pd/Cu Catalysis.

The stereodivergent synthesis of allene compounds bearing α,β-adjacent central chiralities has been realized via the Pd/Cu-catalyzed dynamic kinetic asymmetric alkylation of racemic allenylic esters. The matched reactivity of bimetallic catalytic system enables the challenging reaction of racemic aryl-substituted allenylic acetates with sterically crowded aldimine esters smoothly under mild reaction conditions. Various chiral non-natural amino acids bearing a terminal allenyl group are easily synthesized in high yields and with excellent diastereo- and enantioselectivities (up to >20 : 1 dr, >99 % ee). Importantly, all four stereoisomers of the product can be readily accessed by switching the configurations of the two chiral metal catalysts. Furthermore, the easy interconversion between the uncommon η3 -butadienyl palladium intermediate featuring a weak C=C/Pd coordination bond and a stable Csp2 -Pd bond is beneficial for the dynamic kinetic asymmetric transformation process (DyKAT).

Stereodivergent Construction of 1,4‐Nonadjacent Stereocenters via Hydroalkylation of Racemic Allylic Alcohols Enabled by Copper/Ruthenium Relay Catalysis

AbstractAn unprecedented hydroalkylation of racemic allylic alcohols and racemic ketimine esters enabled by Cu/Ru relay catalysis has been developed via merging the ruthenium‐catalyzed asymmetric borrowing‐hydrogen reaction with a copper‐catalyzed asymmetric Michael addition in a one‐pot procedure. The current method enables the efficient preparation of highly functionalized δ‐hydroxyesters bearing 1,4‐nonadjacent stereocenters in good yields with high levels of diastereoselectivity and excellent enantioselectivity under mild reaction conditions. The full complement of the four stereoisomers of hydroalkylation products could be readily accessed by orthogonal permutations of two chiral metal catalysts. The current work highlights the power of relay catalysis for the stereodivergent construction of 1,4‐nonadjacent stereocenters that were otherwise inaccessible.

Stereodivergent access to rocaglaol enabled by dual catalytic asymmetric allylation

In a recent issue of Chem , Liu and Feng et al. report a stereodivergent allylation of benzofuran-3( 2H )-one catalyzed by two chiral metal catalysts, a phosphoramidite-Ir complex and an N,N′ -dioxide-ligated Lewis acid, and its application to the selective total synthesis of eight stereoisomers of rocaglaol, one of the flavagline-family bioactive molecules. In a recent issue of Chem , Liu and Feng et al. report a stereodivergent allylation of benzofuran-3( 2H )-one catalyzed by two chiral metal catalysts, a phosphoramidite-Ir complex and an N,N′ -dioxide-ligated Lewis acid, and its application to the selective total synthesis of eight stereoisomers of rocaglaol, one of the flavagline-family bioactive molecules.

Porous Silica Support for Immobilizing Chiral Metal Catalyst: Unravelling the Activity of Catalyst on Asymmetric Organic Transformations

AbstractThe role of chiral metal catalysts in asymmetric reactions has developed a new forte for researchers worldwide to boost chiral synthesis in various sectors. By controlling specific interactions among chiral ligands, metal catalysts and the support material, one can design a more selective and efficient chiral heterogeneous catalytic system. Silica has been extensively used as support material in various heterogeneous systems due to its activity, stability, better recovery, and recyclability. This review details recent advances in preparation of the silica suppported chiral catalysts and their applications for various chiral transformatios such as Aldol reaction, Henry reaction, transfer hydrogenation, epoxidation, Passerini reaction etc. The review also covers different mechanisms of immobilization viz., adsorption, electrostatic and covalent interactions. The interaction mechanism of chiral metal catalyst with silica support and factors like matrix pore size and ligand confinement that influence the catalytic performance of enantioselective transformations have also been discussed.

Synthesis of P- and S-Stereogenic Compounds via Enantioselective C–H Functionalization

AbstractTransition metal-catalyzed enantioselective C–H functionalization has emerged as an efficient and powerful strategy to access various chiral molecules. Recently, this strategy has also provided a complementary pathway to the construction of P- and S-stereogenic compounds. In this short review, we summarize the development and applications of various catalytic systems: Pd(II)/mono-N-protected amino acids (MPAA), Pd(0)/trivalent phosphorus chiral ligands, chiral cyclopentadienyl-ligated metal catalysts [CpxM(III)] (M = Rh, Ir), half-sandwich d6 Ir(III) and Ru(II) with a chiral carboxylic acid (CCA) ligand, Ir(I)/chiral bidentate boryl ligand, and Ir(I)/chiral cation, for accessing these chiral compounds via enantioselective C–H functionalization. 1 Introduction2 Pd(II)/Mono-N-protected Amino Acids3 Pd(0)/Trivalent Phosphorus Chiral Ligands4 Chiral Cyclopentadienyl-Ligated Metal Catalysts [CpxM(III)] (M = Rh, Ir)5 Half-sandwich d6 Ir(III) and Ru(II) with a Chiral Carboxylic Acid (CCA) Ligand6 Ir(I)/Chiral Bidentate Boryl Ligand7 Ir(I)/Chiral Cation8 Conclusion and Outlook

The Synthesis of Nucleoside 2',3'-Cyclic Monophosphate Analogs with Regio- and Stereospecificity.

This article presents a new method for the rapid, stereoselective and regioselective synthesis of nucleoside 2',3'-O,O-phosphorothioate and 2',3'-O,O-phosphoroselenoate molecules. The method avoids the use of protection groups, chiral reagents, and chiral metal catalysts, as well as complicated chiral separations. This synthetic method has been applied successfully to all of the natural nucleosides. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Preparation of 2-chloro-1,3,2-dithiophospholane (6) Basic Protocol 2: Preparation of 2-cyanoethoxy-thio-dithiophospholane (8) Basic Protocol 3: Preparation of 2-cyanoethoxy-seleno-dithiophospholane (9) Basic Protocol 4: Preparation of uridine-2',3'-O,O-phosphorothioate (Sp, exo; 1A) Basic Protocol 5: Preparation of uridine-2',3'-O,O-phosphoroselenoate (Sp, exo; 11) Basic Protocol 6: Preparation of adenosine-2',3'-O,O-phosphorothioate (Sp, exo; 12) Basic Protocol 7: Preparation of thymidine-2',3'-O,O-phosphorothioate (Sp, exo; 13) Basic Protocol 8: Preparation of cytosine-2',3'-O,O-phosphorothioate (Sp, exo; 14) Basic Protocol 9: Preparation of guanosine-2',3'-O,O-phosphorothioate (Sp, exo; 15).

Swollen-induced in-situ encapsulation of chiral silver catalysts in cross-linked polysiloxane elastomers: Homogeneous reaction and heterogeneous separation

The immobilization of molecular catalysts to fabricate heterogeneous catalysts for catalytic asymmetric transformations is extremely important and has attracted great attentions. Herein we developed a simple and new strategy for the heterogenization of homogeneous molecular complexes into the cross-linked polymer. It is demonstrated for the first time that the cross-linked polysiloxane elastomers can be applied for the swollen-induced in-situ encapsulation of homogeneous catalysts with or without chiral ligands. The swollen-induced in-situ encapsulation of silver catalyst system in the cross-linked polysiloxane elastomers led to the formation of silicone rubber-based hierarchically porous that could be used in asymmetric [3+2] cycloaddition, asymmetric tandem conjugate addition−elimination reaction and oxidation of hydrosilanes to silanols. The swollen-induced in-situ encapsulation of chiral silver complex in the cross-linked polysiloxane elastomers was proved to be easily recycled by filtration or pick-up and reused by several times. The simplest heterogeneous catalysis by the strategy of swollen-induced in-situ encapsulation can be extended to the encapsulation of chiral metal catalysts into different polymeric materials for the heterogenization of homogeneous catalysis.

Asymmetric Synthesis of Isoxazol-5-ones and Isoxazolidin-5-ones

AbstractIsoxazol-5-ones and isoxazolidin-5-ones represent two important classes of heterocycles, with several applications as bioactive compounds and as versatile building blocks for further transformations. Unlike the parent aromatic isoxazoles, the presence of one or two stereocenters in the ring renders their asymmetric construction particularly important. In this review, starting from the description of general features and differences between these two related compound families, we present an overview on the most important enantioselective synthesis strategies to access these heterocycles. Both chiral metal catalysts and organocatalysts have recently been successfully employed for this task and some of the most promising approaches will be discussed.1 Introduction2 Isoxazol-5-ones as Nucleophiles2.1 Isoxazol-5-ones as C-Nucleophiles2.2 Isoxazol-5-ones as N-Nucleophiles2.3 Isoxazol-5-ones as C-Nucleophiles in Cyclization Processes3 Asymmetric Construction of Isoxazolidin-5-ones3.1 Enantioselective α-Functionalizations of Isoxazolidin-5-ones4 Arylideneisoxazol-5-ones in Conjugated Addition5 Conclusions

The Use of Domino Reactions for the Synthesis of Chiral Rings

This short review highlights the recent developments reported in the last four years on the asymmetric construction of chiral rings based on enantioselective domino reactions promoted by chiral metal catalysts.1 Introduction2 Formation of One Ring Containing One Nitrogen Atom3 Formation of One Ring Containing One Oxygen/Sulfur Atom4 Formation of One Ring Containing Several Heterocyclic Atoms5 Formation of One Carbon Ring6 Formation of Two Rings7 Conclusion

Catalytic Asymmetric Reactions with N-Metallated Azomethine Ylides.

Optically active nitrogen-containing compounds have attracted substantial attention due to their ubiquity in the cores of natural products and bioactive molecules. Among the various synthetic approaches to nitrogenous frameworks, catalytic asymmetric 1,3-dipolar cycloadditions are one of the most attractive methods because of their powerful ability to rapidly construct various chiral N-heterocycles. In particular, N-metallated azomethine ylides, common and readily available 1,3-dipoles, have been extensively applied in dipolar cycloaddition reactions. Despite the fact that asymmetric transformations of azomethine ylides have been investigated for decades, most of the efforts have been directed toward the preparation of pyrrolidines using glycinate-derived α-unsubstituted aldimine esters as the precursors of the azomethine ylides. While α-substituted azomethine ylides derived from amino esters other than glycinate have seldom been harnessed, the construction of non-five-membered chiral N-heterocycles via 1,3-dipolar cycloadditions remains underexplored. In addition, the asymmetric α-functionalization of aldimine esters to prepare acyclic nitrogenous compounds such as α-amino acids, in which an in situ-generated N-metallated azomethine ylide serves as the nucleophile, has not been sufficiently described.In this Account, we mainly discuss the achievements we have made in the past decade toward broadening the applications of N-metallated azomethine ylides for the preparation of nitrogen-containing compounds. We began our investigation with the design and synthesis of a new type of chiral ligand, TF-BiphamPhos, which not only coordinates with Lewis acids to activate dipolar species but also serves as an H-bond donor to increase the reactivity of dipolarophiles with significantly enhanced stereochemical control. Using the Cu(I) or Ag(I)/TF-BiphamPhos complex as the catalyst, we achieved highly stereoselective (3+2) cycloadditions of glycinate and non-glycinate-derived azomethine ylides with diverse dipolarophiles, producing a variety of enantioenriched pyrrolidines with multiple stereocenters in a single step. To further expand the synthetic utility of N-metallated azomethine ylides, we successfully developed higher order cycloadditions with fulvenes, tropone, 2-acyl cycloheptatrienes, and pyrazolidinium ylides serving as the reaction partner, and this reaction provides straightforward access to enantioenriched fused piperidines, bridged azabicyclic frameworks, and triazines via (3+6)- and (3+3)-type cycloadditions. Using N-metallated azomethine ylides as the nucleophile, we realized Cu(I)-catalyzed asymmetric 1,4-Michael additions with α,β-unsaturated bisphosphates/Morita-Baylis-Hillman products, furnishing an array of structurally diverse unnatural α-amino acids. Based on the strategy of synergistic activation, we achieved highly efficient dual Cu/Pd and Cu/Ir catalysis for the α-functionalization of aldimine esters via the asymmetric allylic/allenylic alkylation of N-metallated azomethine ylides. Notably, Cu/Ir catalysis allowed the stereodivergent synthesis of α,α-disubstituted α-amino acids via a branched allylic alkylation reaction, in which the two distinct chiral metal catalysts independently have full stereochemical control over the corresponding nucleophile and electrophile. Furthermore, an expedient and stereodivergent preparation of biologically important tetrahydro-γ-carbolines was realized through a Cu/Ir-catalyzed cascade allylation/iso-Pictet-Spengler cyclization. In addition, when the steric congestion in the allylation intermediates was increased, the combined Cu/Ir catalysts provided an asymmetric cascade allylation/2-aza-Cope rearrangement, producing various optically active homoallylic amines with impressive results.

Stereodivergent Pd/Cu Catalysis for the Dynamic Kinetic Asymmetric Transformation of Racemic Unsymmetrical 1,3-Disubstituted Allyl Acetates.

A stereodivergent Pd/Cu catalyst system has been developed for the unprecedented dynamic kinetic asymmetric transformation (DyKAT) of racemic unsymmetrical 1,3-disubstituted allylic acetates with prochiral aldimine esters. A series of α,α-disubstituted α-amino acids bearing vicinal stereocenters were easily prepared with excellent enantioselectivities (up to >99% ee) and diastereoselectivities (up to >20:1 dr). Moreover, all four stereoisomers of the product can be readily obtained simply by switching the configurations of the two chiral metal catalysts. Furthermore, the present work highlights the power of synergistic Pd/Cu catalysis consisting of two common bidentate chiral ligands for stereodivergent synthesis.