Publications by authors named "Xumu Zhang"

222 Publications

Copper-Catalyzed Enantioselective 1,2-Reduction of Cycloalkenones.

Org Lett 2021 Jul 13. Epub 2021 Jul 13.

Department of Chemistry and State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.

We report an asymmetric 1,2-reduction of cyclic α,β-unsaturated ketones to access various enantiomerically enriched cyclic allylic alcohols under mild conditions, catalyzed by in situ generated copper hydride ligated with ()-DTBM-C*-TunePhos. α-Brominated cycloalkenones were reduced with excellent enantioselectivities of up to 98% ee, while substrates that were without α-substituents were reduced chemoselectively, with moderate enantioselectivities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.1c01744DOI Listing
July 2021

Concise, scalable and enantioselective total synthesis of prostaglandins.

Nat Chem 2021 Jul 27;13(7):692-697. Epub 2021 May 27.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen, China.

Prostaglandins are among the most important natural isolates owing to their broad range of bioactivities and unique structures. However, current methods for the synthesis of prostaglandins suffer from low yields and lengthy steps. Here, we report a practicability-oriented synthetic strategy for the enantioselective and divergent synthesis of prostaglandins. In this approach, the multiply substituted five-membered rings in prostaglandins were constructed via the key enyne cycloisomerization with excellent selectivity (>20:1 d.r., 98% e.e.). The crucial chiral centre on the scaffold of the prostaglandins was installed using the asymmetric hydrogenation method (up to 98% yield and 98% e.e.). From our versatile common intermediates, a series of prostaglandins and related drugs could be produced in two steps, and fluprostenol could be prepared on a 20-gram scale.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41557-021-00706-1DOI Listing
July 2021

Chiral Tridentate Ligands in Transition Metal-Catalyzed Asymmetric Hydrogenation.

Chem Rev 2021 Jul 20;121(13):7530-7567. Epub 2021 May 20.

Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen 518055, China.

Asymmetric hydrogenation (AH) of double bonds has been one of the most effective methods for the preparation of chiral molecules and for the synthesis of important chiral building blocks. In the past 60 years, noble metals with bidentate ligands have shown marvelous reactivity and enantioselectivity in asymmetric hydrogenation of a series of prochiral substrates. In recent years, developing chiral tridentate ligands has played an increasingly important role in AH. With modular frameworks and a variety of functionalities on the side arms, chiral tridentate ligand complexes enable both reactivities and stereoselectivities. Although great achievements have been made for noble metal catalysts with chiral tridentate ligands since the 1990s, the design of chiral tridentate ligands for earth abundant metal catalysts has still been in high demand. This review summarizes the development of chiral tridentate ligands for homogeneous asymmetric hydrogenation. The philosophy of ligand design and the reaction mechanisms are highlighted and discussed as well.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.chemrev.1c00075DOI Listing
July 2021

Correction to Copper-Catalyzed Asymmetric Hydrosilylation of β-Nitroethyl Aryl Ketones.

Org Lett 2021 May 13;23(9):3799. Epub 2021 Apr 13.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen 510855, People's Republic of China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.1c01119DOI Listing
May 2021

Enantioselective Hydrogenation of Tetrasubstituted α,β-Unsaturated Carboxylic Acids Enabled by Cobalt(II) Catalysis: Scope and Mechanistic Insights.

Angew Chem Int Ed Engl 2021 05 7;60(20):11384-11390. Epub 2021 Apr 7.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen, 518000, China.

Chiral carboxylic acids are important compounds because of their prevalence in pharmaceuticals, natural products and agrochemicals. Asymmetric hydrogenation of α,β-unsaturated carboxylic acids has been widely recognized as one of the most efficient synthetic approaches to afford such compounds. Although related asymmetric hydrogenation of di- and trisubstituted unsaturated acids with noble metals is well established, asymmetric hydrogenation of challenging tetrasubstituted α,β-unsaturated carboxylic acids is rarely reported. We demonstrate enantioselective hydrogenation of cyclic and acyclic tetrasubstituted α,β-unsaturated carboxylic acids via cobalt(II) catalysis. This protocol showed broad substrate scope and gave chiral carboxylic acids in good yields with excellent enantiocontrol (up to 98 % yield and 99 % ee). Combined experimental and computational mechanistic studies support a Co catalytic cycle involving migratory insertion and σ-bond metathesis processes. DFT calculations reveal that enantioselectivity may originate from the steric effect between the phenyl groups of the ligand and the substrate.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202016705DOI Listing
May 2021

Asymmetric Transfer Hydrogenation of α-Substituted-β-Keto Carbonitriles via Dynamic Kinetic Resolution.

J Am Chem Soc 2021 02 2;143(6):2477-2483. Epub 2021 Feb 2.

Department of Chemistry, Southern University of Science and Technology, Shenzhen, People's Republic of China.

A catalytic protocol for the enantio- and diastereoselective reduction of α-substituted-β-keto carbonitriles is described. The reaction involves a DKR-ATH process with the simultaneous construction of β-hydroxy carbonitrile scaffolds with two contiguous stereogenic centers. A wide range of α-substituted-β-keto carbonitriles were obtained in high yields (94%-98%) and excellent enantio- and diastereoselectivities (up to >99% ee, up to >99:1 dr). The origin of the diastereoselectivity was also rationalized by DFT calculations. Furthermore, this methodology offers rapid access to the pharmaceutical intermediates of Ipenoxazone and Tapentadol.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/jacs.0c13273DOI Listing
February 2021

Remdesivir Metabolite GS-441524 Effectively Inhibits SARS-CoV-2 Infection in Mouse Models.

J Med Chem 2021 Feb 1. Epub 2021 Feb 1.

Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, College of Science, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.

The outbreak of coronavirus disease 2019 (COVID-19) has resulted in a global pandemic due to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At the time of this manuscript's publication, remdesivir is the only COVID-19 treatment approved by the United States Food and Drug Administration. However, its effectiveness is still under question due to the results of the large Solidarity Trial conducted by the World Health Organization. Herein, we report that the parent nucleoside of remdesivir, GS-441524, potently inhibits the replication of SARS-CoV-2 in Vero E6 and other cell lines. Challenge studies in both an AAV-hACE2 mouse model of SARS-CoV-2 and in mice infected with murine hepatitis virus, a closely related coronavirus, showed that GS-441524 was highly efficacious in reducing the viral titers in CoV-infected organs without notable toxicity. Our results support that GS-441524 is a promising and inexpensive drug candidate for treating of COVID-19 and other CoV diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jmedchem.0c01929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875336PMC
February 2021

Asymmetric hydrogenation catalyzed by first-row transition metal complexes.

Chem Soc Rev 2021 Mar 22;50(5):3211-3237. Epub 2021 Jan 22.

Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, 1088 Xueyuan Road, Shenzhen, 518055, China.

This review provides a comprehensive view of the application of first-row transition metals in asymmetric hydrogenation and asymmetric transfer hydrogenation. The catalytic behavior of 3d metals is significantly different from that of 4d and 5d metals. The replacement of noble metals with first-row transition metals has encountered challenges such as different reaction mechanisms and unexpected deactivation of the catalyst. The potential involvement of a single-electron process has been the most notorious feature of first-row metals. This review aims to give readers a picture of how first-row transition metals catalyze hydrogenation reactions and the corresponding enantioinduction models. Although this article is partitioned according to the substrate type, it is mechanism-oriented and is focused on catalytic systems. A certain catalytic system could be applied in the hydrogenation of different types of double bonds. Similarities within first-row metals and differences from their 4d and 5d congeners were emphasized.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cs00082eDOI Listing
March 2021

Nickel-Catalyzed Asymmetric Hydrogenation of Cyclic Alkenyl Sulfones, Benzo[]thiophene 1,1-Dioxides, with Mechanistic Studies.

Org Lett 2021 Feb 20;23(3):668-675. Epub 2021 Jan 20.

Engineering Research Center of Organosilicon Compounds & Materials, Ministry of Education, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei 430072, China.

A highly efficient catalytic system based on the cheap transition metal nickel for the asymmetric hydrogenation of challenging cyclic alkenyl sulfones, 3-substituted benzo[]thiophene 1,1-dioxides, was first successfully developed. A series of hydrogenation products, chiral 2,3-dihydrobenzo[]thiophene 1,1-dioxides, were obtained in high yields (95-99%) with excellent enantioselectivities (90-99% ee). According to the results of nonlinear effect studies, deuterium-labeling experiments, and DFT calculation investigations, a reasonable catalytic mechanism for this nickel-catalyzed asymmetric hydrogenation was provided, which displayed that the two added hydrogen atoms of the hydrogenation products could be from H through the insertion of Ni-H and subsequent hydrogenolysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.0c03723DOI Listing
February 2021

Highly Chemo- and Enantioselective Rh-Catalyzed Hydrogenation of β-Sulfonyl-α,β-unsaturated Ketones: Access to Chiral γ-Ketosulfones.

Org Lett 2021 Jan 22;23(1):19-24. Epub 2020 Dec 22.

Key Laboratory of Biomedical Polymers, Engineering Research Center of Organosilicon Compounds & Materials, Ministry of Education, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei 430072, P.R. China.

Rh-catalyzed highly chemo- and enantioselective hydrogenation of β-sulfonyl-α,β-unsaturated ketones was first successfully developed. Remarkably, a variety of enantioenriched γ-ketosulfones were generated in good to high yields with excellent chemo/enantioselectivities (82-99% yields, >99:1 chemoselectivity, 88 to >99% ee). Moreover, the gram-scale asymmetric hydrogenation was carried out smoothly in 97% yield and 97% ee. Preliminary DFT computations furnished a reasonable explanation for the high chemoselectivity and enantioselectivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.0c03517DOI Listing
January 2021

Design of oxa-spirocyclic PHOX ligands for the asymmetric synthesis of lorcaserin via iridium-catalyzed asymmetric hydrogenation.

Chem Commun (Camb) 2021 Jan 10;57(2):195-198. Epub 2020 Dec 10.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen 518000, People's Republic of China.

Phosphine-oxazoline (PHOX) ligands are a very important class of privileged ligands in asymmetric catalysis. A series of highly rigid oxa-spiro phosphine-oxazoline (O-SIPHOX) ligands based on O-SPINOL was synthesized efficiently, and their iridium complexes were synthesized by coordination of the O-SIPHOX ligands to [Ir(cod)Cl] in the presence of sodium tetrakis-3,5-bis(trifluoromethyl)phenylborate (NaBArF). The cationic iridium complexes showed high reactivity and excellent enantioselectivity in the asymmetric hydrogenation of 1-methylene-tetrahydro-benzo[d]azepin-2-ones (up to 99% yield and up to 99% ee). A key intermediate of the anti-obesity drug lorcaserin could be efficiently synthesized using this protocol.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cc06311hDOI Listing
January 2021

Ni-Catalyzed asymmetric reduction of α-keto-β-lactams via DKR enabled by proton shuttling.

Chem Commun (Camb) 2020 Dec 27;56(99):15557-15560. Epub 2020 Nov 27.

School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, People's Republic of China.

Chiral α-hydroxy-β-lactams are key fragments of many bioactive compounds and antibiotics, and the development of efficient synthetic methods for these compounds is of great value. The highly enantioselective dynamic kinetic resolution (DKR) of α-keto-β-lactams was realized via a novel proton shuttling strategy. A wide range of α-keto-β-lactams were reduced efficiently and enantioselectively by Ni-catalyzed asymmetric hydrogenation, providing the corresponding α-hydroxy-β-lactam derivatives with high yields and enantioselectivities (up to 92% yield, up to 94% ee). Deuterium-labelling experiments indicate that phenylphosphinic acid plays a pivotal role in the DKR of α-keto-β-lactams by promoting the enolization process. The synthetic potential of this protocol was demonstrated by its application in the synthesis of a key intermediate of Taxol and (+)-epi-Cytoxazone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cc05599aDOI Listing
December 2020

Asymmetric Hydrogenation of 2-Aryl-3-phthalimidopyridinium Salts: Synthesis of Piperidine Derivatives with Two Contiguous Stereocenters.

Org Lett 2020 11 4;22(22):8882-8887. Epub 2020 Nov 4.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen 518000, People's Republic of China.

Asymmetric hydrogenation of 2-aryl-3-phthalimidopyridinium salts catalyzed by the Ir/SegPhos catalytic system was described, leading to the corresponding chiral piperidine derivatives bearing two contiguous chiral centers, with high levels of enantioselectivities and diastereoselectivities. A gram-scale experiment has demonstrated the utility of this approach. The phthaloyl group could be easily removed and then smoothly converted to key intermediate (+)-CP-99994 as one of the neurokinin 1 receptor antagonists.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.0c03261DOI Listing
November 2020

Chiral Electron-Rich PNP Ligand with a Phospholane Motif: Structural Features and Application in Asymmetric Hydrogenation.

Org Lett 2020 Nov 29;22(22):8796-8801. Epub 2020 Oct 29.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen 518055, China.

Despite the remarkable reactivity that was achieved by a series of transition-metal catalysts with a PNP type ligand, the electron-rich chiral PNP ligands have still been rarely reported because of the difficulties in synthesis and the nature of air-sensitivity. Herein, we report a novel chiral PNP ligand (Heng-PNP) with both a rigid backbone and a bulky -butyl group on the phospholane motif. We successfully obtained its divalent iron complex. The chiral environment of its Ir(III) complex was also discussed with quadrant analysis. This tridentate ligand was applied in iridium-catalyzed asymmetric hydrogenation of challenging diaryl ketones: up to 98% and 500 TON are achieved. Computational study showed that the twist of conjugate aryl group in the substrate (induced by the special chiral pocket of Ir/Heng-PNP complex) leads to the energy difference in the enantiodetermining step.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.0c03159DOI Listing
November 2020

Iridium-Catalyzed Asymmetric Hydrogenation of α-Fluoro Ketones via a Dynamic Kinetic Resolution Strategy.

Org Lett 2020 09 31;22(18):7230-7233. Epub 2020 Aug 31.

Shenzhen Grubbs Institute and Department of Chemistry, Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China.

The discrimination of a fluorine atom from a hydrogen atom has been challenging in asymmetric catalysis. We herein report iridium-catalyzed hydrogenation of α-fluoro ketones using a strategy of dynamic kinetic resolution. Both enantiomeric and diastereomeric selectivities were satisfactory in the preparation of β-fluoro alcohols. The DFT calculation revealed a C-F···Na charge-dipole interaction in the transition state of hydride transfer. This noncovalent interaction would be responsible for the diastereomeric control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.0c02565DOI Listing
September 2020

Noncovalent Interaction-Assisted Ferrocenyl Phosphine Ligands in Asymmetric Catalysis.

Acc Chem Res 2020 09 27;53(9):1905-1921. Epub 2020 Aug 27.

Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen 518000, P.R. China.

Noncovalent interactions are ubiquitous in nature and are responsible for the precision control in enzyme catalysis via the cooperation of multiple active sites. Inspired by this principle, noncovalent interaction-assisted transition metal catalysis has emerged recently as a powerful tool and has attracted intense interest. However, it is still highly desirable to develop efficient and operationally convenient ligands along this line with new structural motifs. Based on the specific nature of hydrogen bonding and ion pairing interactions, we developed a series of noncovalent interaction-assisted chiral ferrocenyl phosphine ligands, including Zhaophos, Wudaphos, and miscellaneous SPO-Wudaphos. Due to the assistance of noncovalent interactions, this catalytic mode is capable of achieving transition metal catalyzed asymmetric hydrogenation and other transformations with remarkable improvement of reactivity and selectivity. In some specific challenging cases, this probably represents one of the most productive methods. Moreover, these ligands are easily prepared, air stable, and highly tunable, meeting the requirements of industrial application.In this Account, we give a concise review of recent advances in asymmetric catalysis. By means of hydrogen bonding interactions, Rh- and Ir-Zhaophos complexes exhibited excellent activities and enantioselectivities in asymmetric hydrogenation of a wide range of substrates: C═C bonds of substituted conjugate alkenes with neutral hydrogen bond acceptors, including nitro groups, carbonyl groups (ketones, esters, amides, maleinimides, and anhydrides), ethers, and sulfones; C═N bonds of substituted iminium salts with chloride as an anionic hydrogen bond acceptor, including N-H imines and cyclic imines; -heteroaromatic compounds with HCl as an additive, including unprotected quinolines, isoquinolines, and indoles; carbocation of substituted oxocarbenium ions. By means of ion pairing interactions, Rh-Wudaphos complexes enabled the catalytic asymmetric hydrogenation of α-substituted unsaturated carboxylic acids, carboxy-directed α,α-disubstituted terminal olefins, and sodium α-arylethenylsulfonates. Rh-SPO-Wudaphos utilized both hydrogen bonding and ion pairing interactions in asymmetric hydrogenation of α-substituted unsaturated carboxylic acids and phosphonic acids. In addition, Zhaophos has achieved highly selective intramolecular reductive amination and inter- and intramolecular asymmetric decarboxylative allylation. Investigations into mechanism implied that noncovalent interactions were involved in the catalytic cycle and played a critical role for both high reactivity and selectivity. Notably, a rare ionic hydrogenation pathway has been proposed in some cases. Furthermore, these catalytic systems have been used in the gram-scale synthesis of natural products and pharmaceuticals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.accounts.0c00347DOI Listing
September 2020

Asymmetric Reductive Amination/Ring-Closing Cascade: Direct Synthesis of Enantioenriched Biaryl-Bridged NH Lactams.

Org Lett 2020 08 11;22(16):6479-6483. Epub 2020 Aug 11.

Guangdong Provincial Key Laboratory of Catalysis, Department of Chemistry, Southern University of Science and Technology, Shenzhen 518055, China.

We report here a Ru-catalyzed enantioselective synthesis of biaryl-bridged NH lactams through asymmetric reductive amination and a spontaneous ring-closing cascade from keto esters and NHOAc with H as reductant. The reaction features broad substrate generality and high enantioselectivities (up to >99% ee). To showcase the practical utility, a highly enantioselective synthesis of 5-ethylindolobenzazepinone , a promising antimitotic agent, has been rapidly completed. Furthermore, the amide group in the products enables versatile elaborations through directed C-H functionalization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.0c02282DOI Listing
August 2020

Direct catalytic asymmetric synthesis of α-chiral primary amines.

Chem Soc Rev 2020 Sep 15;49(17):6141-6153. Epub 2020 Jul 15.

Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen 518055, China.

α-Chiral primary amines are one among the most valuable and versatile building blocks for the synthesis of numerous amine-containing pharmaceuticals and natural compounds. They also serve as chiral ligands or organo-catalysts for asymmetric catalysis. However, most of the existing chemocatalytic methods toward enantiopure primary amines rely on multistep manipulations on N-substituted substrates, which are not ideally atom-economical and cost-effective. Among the catalytic methods including the asymmetric transformations of the pre-prepared or in situ formed NH imines, biomimetic chemocatalysis inspired by enzymatic transaminations has recently emerged as an appealing and straightforward method to access chiral primary amines. This tutorial review highlights the state-of-the-art catalytic methods for the direct asymmetric synthesis of α-chiral primary amines and demonstrates their utility in the construction of molecular complexities, which may attract extensive attention and inspire applications in synthetic and medicinal chemistry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9cs00921cDOI Listing
September 2020

Facile Synthesis of Enantiopure Sugar Alcohols: Asymmetric Hydrogenation and Dynamic Kinetic Resolution Combined.

Angew Chem Int Ed Engl 2020 10 18;59(41):18166-18171. Epub 2020 Aug 18.

Guangdong Provincial Key Laboratory of Catalysis, Department of Chemistry, Southern University of Science and Technology, 1088 Xueyuan Road, Shenzhen, 518055, China.

An unprecedented Ir/f-amphox-catalyzed asymmetric hydrogenation of racemic 2,3-syn-dihydroxy-1,4-diones is presented involving dynamic kinetic resolution, which produces (1R,2R,3R,4R)-tetraols. This protocol constitutes an efficient and straightforward approach to accessing sugar alcohols bearing four contiguous stereocenters. The strategy exhibits various advantages over existing methods, including excellent yields (up to 98 %), exceptional stereoselectivities (up to 99:1 dr, 99.9 % ee), operational simplicity and substrate generality. Moreover, the nature of the reaction was revealed as a stepwise transformation by in situ Fourier-transform infrared spectroscopy and isolation of intermediates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.202006661DOI Listing
October 2020

Cobalt-catalyzed highly enantioselective hydrogenation of α,β-unsaturated carboxylic acids.

Nat Commun 2020 06 26;11(1):3239. Epub 2020 Jun 26.

Department of Chemistry and Shenzhen Grubbs Institute, Southern University of Science and Technology, 518000, Shenzhen, China.

Asymmetric hydrogenation of α,β-unsaturated acids catalyzed by noble metals has been well established, whereas, the asymmetric hydrogenation with earth-abundant-metal was rarely reported. Here, we describe a cobalt-catalyzed asymmetric hydrogenation of α,β-unsaturated carboxylic acids. By using chiral cobalt catalyst bearing electron-donating diphosphine ligand, high activity (up to 1860 TON) and excellent enantioselectivity (up to >99% ee) are observed. Furthermore, the cobalt-catalyzed asymmetric hydrogenation is successfully applied to a broad spectrum of α,β-unsaturated carboxylic acids, such as various α-aryl and α-alkyl cinnamic acid derivatives, α-oxy-functionalized α,β-unsaturated acids, α-substituted acrylic acids and heterocyclic α,β-unsaturated acids (30 examples). The synthetic utility of the protocol is highlighted by the synthesis of key intermediates for chiral drugs (6 cases). Preliminary mechanistic studies reveal that the carboxy group may be involved in the control of the reactivity and enantioselectivity through an interaction with the metal centre.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-17057-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319995PMC
June 2020

Asymmetric Hydrogenation of Cationic Intermediates for the Synthesis of Chiral N,O-Acetals.

Chemistry 2020 Sep 7;26(50):11470-11477. Epub 2020 Aug 7.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, 1088 Xueyuan Road, Shenzhen, 518055, P. R. China.

For over half a century, transition-metal-catalyzed homogeneous hydrogenation has been mainly focused on neutral and readily prepared unsaturated substrates. Although the addition of molecular hydrogen to C=C, C=N, and C=O bonds represents a well-studied paradigm, the asymmetric hydrogenation of cationic species remains an underdeveloped area. In this study, we were seeking a breakthrough in asymmetric hydrogenation, with cationic intermediates as targets, and thereby anticipating applying this powerful tool to the construction of challenging chiral molecules. Under acidic conditions, both N- or O-acetylsalicylamides underwent cyclization to generate cationic intermediates, which were subsequently reduced by an iridium or rhodium hydride complex. The resulting N,O-acetals were synthesized with remarkably high enantioselectivity. This catalytic strategy exhibited high efficiency (turnover number of up to 4400) and high chemoselectivity. Mechanistic studies supported the hypothesis that a cationic intermediate was formed in situ and hydrogenated afterwards. A catalytic cycle has been proposed with hydride transfer from the iridium complex to the cationic sp carbon atom being the rate-determining step. A steric map of the catalyst has been created to illustrate the chiral environment, and a quantitative structure-selectivity relationship analysis showed how enantiomeric induction was achieved in this chemical transformation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/chem.202002930DOI Listing
September 2020

Highly Chemo- and Enantioselective Hydrogenation of 2-Substituted-4-oxo-2-alkenoic Acids.

Org Lett 2020 06 10;22(12):4812-4816. Epub 2020 Jun 10.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen 518055, China.

The highly chemo- and enantioselective hydrogenation of ()-2-substituted-4-oxo-2-alkenoic acids was established for the first time using the Rh/JosiPhos complex, affording a series of chiral -substituted--keto acids with excellent results (up to 99% yield and >99% ) and high efficiency (up to 3000 TON). In addition, the importance of this methodology was further demonstrated by a concise and gram-scale synthesis of the anti-inflammatory drug ()-flobufen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.0c01618DOI Listing
June 2020

Asymmetric Linear-Selective Hydroformylation of 1,1-Dialkyl Olefins Assisted by a Steric-Auxiliary Strategy.

Org Lett 2020 06 12;22(11):4523-4526. Epub 2020 May 12.

Shenzhen Grubbs Institute and Department of Chemistry, Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Southern University of Science and Technology, 1088 Xueyuan Road, Shenzhen, 518055, China.

Asymmetric hydroformylation of 1,2-dialkyl olefins was reported. In order to increase the enantiomeric induction, steric auxiliary sulfonyl groups were introduced. Using a Rh/Yanphos complex as catalyst, chiral aldehydes were obtained with high enantioselectivities under mild pressure. The easily removable auxiliary made this method a powerful tool in the preparation of important enantiopure building blocks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.0c01550DOI Listing
June 2020

Synthesis of chiral α-substituted α-amino acid and amine derivatives through Ni-catalyzed asymmetric hydrogenation.

Chem Commun (Camb) 2020 May;56(36):4934-4937

Key Laboratory of Biomedical Polymers, Engineering Research Center of Organosilicon Compounds & Materials, Ministry of Education, College of Chemistry and Molecular Sciences, Suzhou Institute of Wuhan University, Wuhan University, Wuhan, Hubei 430072, P. R. China.

Highly efficient Ni-catalyzed asymmetric hydrogenation of cyclic N-sulfonyl ketimino esters was, for the first time, successfully developed, providing various chiral α-monosubstituted α-amino acid derivatives with excellent results (97-99% yields, 90 to >99% ee). Cyclic N-sulfonyl ketimines were also hydrogenated well to afford chiral amine derivatives with 98-99% yields and 97 to >99% ee. The gram-scale asymmetric hydrogenation was performed well with 85% yield and 99% ee using only 0.2 mol% catalyst.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cc01220cDOI Listing
May 2020

Direct Synthesis of Chiral NH Lactams via Ru-Catalyzed Asymmetric Reductive Amination/Cyclization Cascade of Keto Acids/Esters.

Org Lett 2020 04 19;22(7):2707-2713. Epub 2020 Mar 19.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen 518055, China.

Lactams with a stereogenic center adjacent to the N atom have existed in many medicinal agents and bioactive alkaloids. Herein we report a broadly applicable synthesis of enantioenriched NH lactams through a one-pot asymmetric reductive amination/cyclization sequence of easily available keto acids/esters. Such cascade processes alleviate the demand for protecting group manipulations as well as intermediate purification. This strategy is capable of constructing enantioenriched lactams and benzo-lactams of a five-, six-, or seven-membered ring in generally high yield and with excellent enantioselectivities (up to 97% ee). Scalable and concise syntheses of key drug intermediates have further displayed the importance of this methodology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.0c00669DOI Listing
April 2020

Rh(iii)-Catalyzed diastereoselective transfer hydrogenation: an efficient entry to key intermediates of HIV protease inhibitors.

Chem Commun (Camb) 2020 Mar 24;56(21):3119-3122. Epub 2020 Feb 24.

School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, People's Republic of China.

A highly efficient diastereoselective transfer hydrogenation of α-aminoalkyl α'-chloromethyl ketones catalyzed by a tethered rhodium complex was developed and successfully utilized in the synthesis of the key intermediates of HIV protease inhibitors. With the current Rh(iii) catalyst system, a series of chiral 3-amino-1-chloro-2-hydroxy-4-phenylbutanes were produced in excellent yields and diastereoselectivities (up to 99% yield, up to 99 : 1 dr). Both diastereomers of the desired products could be efficiently accessed by using the two enantiomers of the Rh(iii) catalyst.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9cc09793gDOI Listing
March 2020

Iridium-Catalyzed Enantioselective Hydrogenation of Oxocarbenium Ions: A Case of Ionic Hydrogenation.

Angew Chem Int Ed Engl 2020 04 24;59(15):6108-6114. Epub 2020 Feb 24.

Shenzhen Grubbs Institute and Department of chemistry, Southern University of Science and Technology, 1088 Xueyuan Road, Shenzhen, 518055, China.

Ionic hydrogenation has not been extensively explored, but is advantageous for challenging substrates such as unsaturated intermediates. Reported here is an iridium-catalyzed hydrogenation of oxocarbenium ions to afford chiral isochromans with high enantioselectivities. A variety of functionalities are compatible with this catalytic system. In the presence of a catalytic amount of the Brønsted acid HCl, an α-chloroether is generated in situ and subsequentially reduced. Kinetic studies suggest first-order kinetics in the substrate and half-order kinetics in the catalyst. A positive nonlinear effect, together with the half kinetic order, revealed a dimerization of the catalyst. Possible reaction pathways based on the monomeric iridium catalyst were proposed and DFT computational studies revealed an ionic hydrogenation pathway. Chloride abstraction and the cleavage of dihydrogen occur in the same step.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.201916677DOI Listing
April 2020

Ruthenium-Catalyzed Direct Asymmetric Reductive Amination of Diaryl and Sterically Hindered Ketones with Ammonium Salts and H.

Angew Chem Int Ed Engl 2020 03 20;59(13):5321-5325. Epub 2020 Feb 20.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen, Guangdong, 518055, P. R. China.

A Ru-catalyzed direct asymmetric reductive amination of ortho-OH-substituted diaryl and sterically hindered ketones with ammonium salts is reported. This method represents a straightforward route toward the synthesis of synthetically useful chiral primary diarylmethylamines and sterically hindered benzylamines (up to 97 % yield, 93->99 % ee). Elaborations of the chiral amine products into bioactive compounds and a chiral ligand were demonstrated through manipulation of the removable and convertible -OH group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/anie.201915459DOI Listing
March 2020

Rhodium-catalyzed asymmetric hydrogenation of exocyclic α,β-unsaturated carbonyl compounds.

Org Biomol Chem 2020 02 15;18(5):856-859. Epub 2020 Jan 15.

Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology, Shenzhen 518000, People's Republic of China.

A highly enantioselective hydrogenation of exocyclic α,β-unsaturated carbonyl compounds catalyzed by Rh/bisphosphine-thiourea (ZhaoPhos) has been developed, giving the corresponding α-chiral cyclic lactones, lactams and ketones with high yields and excellent enantioselectivities (up to 99% yield and 99% ee). Remarkably, the hydrogen bond between the substrate and the catalyst plays a critical role in this transformation. The synthetic utility of this protocol has been demonstrated by efficient synthesis of chiral 3-(4-fluorobenzyl)piperidine, a key chiral fragment of bioactive molecules.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9ob02536gDOI Listing
February 2020

Rhodium-Catalyzed Enantioselective Anti-Markovnikov Hydroformylation of α-Substituted Acryl Acid Derivatives.

Org Lett 2020 02 14;22(3):1108-1112. Epub 2020 Jan 14.

Shenzhen Grubbs Institute and Department of Chemistry , Southern University of Science and Technology , Shenzhen , Guangdong 518000 , China.

Rhodium-catalyzed asymmetric anti-Markovnikov hydroformylation of α-substituted acrylates/acrylamides has been developed. By employing the Rh/(,)-DTBM-YanPhos complex, a series of β-chiral linear aldehydes were obtained in high yields (up to 94% yield) and high enantioselectivities (up to 96% ee). The utility of this methodology is demonstrated by a gram-scale reaction and a concise synthetic route to chiral γ-butyrolactone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.9b04624DOI Listing
February 2020
-->