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1.
Adv Sci (Weinh) ; 11(21): e2400096, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38477439

ABSTRACT

Chiral 1, n-bis(boronate) plays a crucial role in organic synthesis and medicinal chemistry. However, their catalytic and asymmetric synthesis has long posed a challenge in terms of operability and accessibility from readily available substrates. The recent discovery of the C═C bond formation through ß-C elimination of methylenecyclopropanes (MCP) has provided an exciting opportunity to enhance molecular complexity. In this study, the catalyzed asymmetric cascade hydroboration of MCP is developed. By employing different ligands, various homoallylic boronate intermediate are obtained through the hydroboration ring opening process. Subsequently, the cascade hydroboration with HBpin or B2pin2 resulted in the synthesis of enantioenriched chiral 1,3- and 1,4-bis(boronates) in high yields, accompanied by excellent chemo- and enantioselectivities. The selective transformation of these two distinct C─B bonds also demonstrated their application potential in organic synthesis.

2.
Chem Sci ; 14(16): 4413-4417, 2023 Apr 26.
Article in English | MEDLINE | ID: mdl-37123192

ABSTRACT

An enantioselective hydrophosphination of alkenyl isoquinolines is developed by using a copper-chiral diphosphine ligand catalyst. It provides a direct and atom-efficient approach to prepare a variety of chiral phosphines with an isoquinoline unit in good yields and high enantioselectivities. In addition, these chiral phosphine products are useful bidentate P,N-ligands which showed potential application in asymmetric catalysis.

3.
Angew Chem Int Ed Engl ; 62(26): e202303727, 2023 Jun 26.
Article in English | MEDLINE | ID: mdl-37186017

ABSTRACT

Transition metal-catalyzed hydrofunctionalization of methylenecyclopropanes (MCPs) has presented a considerable challenge due to the difficult manipulation of regioselectivity and complicated reaction patterns. Herein, we report a straightforward Pd-catalyzed ring-opening hydrophosphinylation reaction of MCPs via highly selective C-C bond cleavage. This method allows for rapid and efficient access to a wide range of chiral allylic phosphine oxides in good yields and high enantioselectivities. Additionally, density functional theory (DFT) calculations were performed to elucidate the reaction mechanism and the origin of enantioselectivity.


Subject(s)
Cyclopropanes , Palladium , Palladium/chemistry , Cyclopropanes/chemistry , Catalysis
4.
Angew Chem Int Ed Engl ; 62(3): e202215820, 2023 Jan 16.
Article in English | MEDLINE | ID: mdl-36424372

ABSTRACT

A Cu/CPA co-catalytic system has been developed for achieving the direct hydrophosphinylation of alkynes with phosphine oxides in delivering novel axially chiral phosphorus-containing alkenes in high yields and excellent enantioselectivities (up to 99 % yield and 99 % ee). DFT calculations were performed to elucidate the reaction pathway and the origin of enantiocontrol. This streamlined and modular methodology establishes a new platform for the design and application of new axially chiral styrene-phosphine ligands.

5.
Chem Sci ; 13(42): 12498-12502, 2022 Nov 02.
Article in English | MEDLINE | ID: mdl-36382277

ABSTRACT

Nickel-catalyzed asymmetric α-heteroarylation of ketones with fluorinated heteroarenes is reported via C-F bond activation. A series of ketones and 2-fluoropyridine derivatives with different functional groups proceed well to provide the corresponding products containing all-carbon quaternary stereocenters in good yields (up to 99% yield) and high ee values (up to 99% ee). In addition, drug molecule donepezil could also be compatible under the reaction conditions to afford late-stage diversification of pharmaceuticals.

6.
Sci Adv ; 8(22): eabm9603, 2022 06 03.
Article in English | MEDLINE | ID: mdl-35658029

ABSTRACT

Flavanols are privileged heterocyclic compounds in medicinal chemistry. It is notable to develop an efficient and straightforward protocol for accessing chiral flavanols with precise control of the stereocenters. Here, a highly efficient kinetic resolution of chromenes was reported via Cu-catalyzed asymmetric hydroboration. This previously unidentified approach features a one-step synthesis of chiral flavan-3-ols containing two vicinal stereogenic centers via a highly efficient kinetic resolution (s factor up to 1060, >99% ee for most products). In addition, the anti-inflammation effects of these diversified flavan-3-ols were studied by the in vitro experiments and RNA sequencing analysis. These flavan-3-ols showed inhibitory effects on the secretion of pro-inflammation cytokines including interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α), as well as inhibiting the inflammation responses through down-regulating the gene transcriptions closely related to PI3K-Akt signaling pathway and TNF signaling pathway. The results suggested that these newly synthesized flavan-3-ols have the potential to be lead compounds for anti-inflammatory drugs.


Subject(s)
Benzopyrans , Copper/chemistry , Phosphatidylinositol 3-Kinases , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Benzopyrans/pharmacology , Catalysis , Humans , Inflammation/drug therapy
7.
Angew Chem Int Ed Engl ; 61(24): e202202160, 2022 06 13.
Article in English | MEDLINE | ID: mdl-35338562

ABSTRACT

Despite the widespread existence of chiral 1,4-diamines in bioactive molecules and their applications in asymmetric catalysis, the catalytic and asymmetric synthesis of such structures from readily accessible substrates remains a long-standing challenge. Here, we report a Cu-catalyzed asymmetric cascade hydroamination protocol to construct a wide range of chiral 1,4-diamine derivatives in high yields with excellent enatioselectivities (up to 95 % yield and up to >99 % ee). The use of two hydroxylamine esters containing different functionalized amino groups allowed us to increase the complexity of the final 1,4-diamine structures. The desired products could be easily transformed into chiral 1,4-diamines and chiral NH2 -Terfenadine. Mechanistic study demonstrates that this reaction proceeds through hydroamination ring-opening and cascade hydroamination sequence.


Subject(s)
Cyclopropanes , Diamines , Catalysis , Diamines/chemistry , Esters , Stereoisomerism
8.
Angew Chem Int Ed Engl ; 60(52): 27288-27292, 2021 12 20.
Article in English | MEDLINE | ID: mdl-34581469

ABSTRACT

A Pd-catalyzed hydrophosphinylation of alkyl and aryl-oxyallenes with phosphine oxides has been developed for the efficient and rapid construction of a family of chiral allylic phosphine oxides with a diverse range of functional groups. This methodology was further applied in the facile construction of chiral 2H-chromene and later stage functionalization of cholesterol.

9.
Org Biomol Chem ; 19(12): 2663-2667, 2021 03 28.
Article in English | MEDLINE | ID: mdl-33688906

ABSTRACT

A metal-free access to 3-allyl-2-alkoxychromanones by PPh3-catalyzed alkoxy allylation of chromones with MBH carbonates and alcohols is described. This reaction is performed under mild conditions and it shows good functional group tolerance, providing a series of functionalized chromanones in moderate to high yields with excellent diastereoselectivities. Deuterium-labeling experiments to probe a possible mechanism and scale-up reaction were also conducted.

10.
Chem Commun (Camb) ; 56(72): 10552-10555, 2020 Sep 10.
Article in English | MEDLINE | ID: mdl-32785314

ABSTRACT

A multicomponent catalytic reaction between ketones, Morita-Baylis-Hillman (MBH) carbonates and trifluoromethylthiolating agents is devised for straightforwardly accessing two products, α-trifluoromethylthiolated ketones and α-methylene ß-amino esters in a one pot fashion. Particularly noteworthy is that the trifluoromethylthiolating reagent is employed as both the nitrogen and SCF3 source initiated by DABCO. This mild one pot strategy enjoys atom- and step-economic attractiveness, for direct introduction of an SCF3 group onto a variety of acyclic ketones, which have been considered as less effective and less developed substrates.

11.
Chem Commun (Camb) ; 56(55): 7573-7576, 2020 Jul 09.
Article in English | MEDLINE | ID: mdl-32510073

ABSTRACT

An efficient Rh/Pd relay catalyzed intermolecular and cascade intramolecular hydroamination for the synthesis of exclusive trans 1-indolyl dihydronaphthalenols (up to 88% yield, 99% ee) is described under mild conditions. Moreover, the in silico and in vitro screening showed that the novel 1-indolyl dihydronaphthalenol products are potent lead compounds for treating inflammation disease.


Subject(s)
Anti-Inflammatory Agents/chemical synthesis , Indoles/chemistry , Palladium/chemistry , Rhodium/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Catalysis , Cell Survival/drug effects , Cytokines/metabolism , Indoles/chemical synthesis , Indoles/pharmacology , Interleukin-1beta/metabolism , Lipopolysaccharides/pharmacology , Macrophages/cytology , Macrophages/drug effects , Macrophages/metabolism , Mice , Naphthalenes/chemistry , RAW 264.7 Cells , Stereoisomerism
12.
Chem Sci ; 11(28): 7451-7455, 2020 Jun 29.
Article in English | MEDLINE | ID: mdl-34123027

ABSTRACT

Despite the importance of P-chiral organophosphorus compounds in asymmetric catalysis, transition metal-catalyzed methods for accessing P-chiral phosphine derivatives are still limited. Herein, a catalytic enantioselective method for the synthesis of P-stereogenic alkenylphosphinates is developed through asymmetric hydrophosphorylation of alkynes. This process is demonstrated for a wide range of racemic phosphinates and leads to diverse P-stereogenic alkenylphosphinates directly.

13.
Nat Commun ; 10(1): 2007, 2019 Apr 26.
Article in English | MEDLINE | ID: mdl-31028262

ABSTRACT

The original PDF version of this Article contained an error in Table 3, in which all chemical structures were omitted and only the numerical data was shown. This has been corrected in the PDF version of the Article. The HTML version was correct from the time of publication.

14.
Nat Commun ; 10(1): 566, 2019 02 04.
Article in English | MEDLINE | ID: mdl-30718716

ABSTRACT

Axially chiral arylpyrroles are key components of pharmaceuticals and natural products as well as chiral catalysts and ligands for asymmetric transformations. However, the catalytic enantioselective construction of optically active arylpyrroles remains a formidable challenge. Here we disclose a highly efficient strategy to access enantioenriched axially chiral arylpyrroles by means of organocatalytic atroposelective desymmetrization and kinetic resolution. Depending on the remote control of chiral catalyst, the arylpyrroles were obtained in high yields and excellent enantioselectivities under mild reaction conditions. This strategy tolerates a wide range of functional groups, providing a facile avenue to approach axially chiral arylpyrroles from simple and readily available starting materials. Selected arylpyrrole products proved to be efficient chiral ligands in asymmetric catalysis and also important precursors for further synthetic transformations into highly functionalized pyrroles with potential bioactivity, especially the axially chiral fully substituted arylpyrroles.

15.
Angew Chem Int Ed Engl ; 58(16): 5343-5347, 2019 Apr 08.
Article in English | MEDLINE | ID: mdl-30786133

ABSTRACT

A highly efficient kinetic resolution and dynamic kinetic resolution of chromene is reported for the first time and they procced by a rhodium-catalyzed asymmetric hydroarylation pathway. This new approach offers versatile access to various chiral 2,3-diaryl-chromanes containing vicinal stereogenic centers, as well as the recovered chiral flavenes, in high yields with excellent ee values (s factor up to 532). Particularly noteworthy is that this strategy can be further extended to the establishment of a dynamic version of the kinetic resolution of chromene acetals and allows complete access to chiral isoflavanes and α-aryl hydrocoumarins.

16.
Org Lett ; 20(20): 6490-6493, 2018 10 19.
Article in English | MEDLINE | ID: mdl-30284837

ABSTRACT

A direct C(sp2)-H thiolation of aromatic amides with disulfides was developed. The coupling reaction proceeds between the thioether radical and cobaltacycle intermediate. This method exhibits a relatively broad substrate scope and high functional group compatibility. A mechanistic study indicates that the cobalt(IV) intermediate is probably formed during the course of the reaction. The thiolation product can be transformed to Quetiapine, which is an atypical antipsychotic agent approved for the treatment of schizophrenia and bipolar disorder.

17.
Science ; 361(6407)2018 09 14.
Article in English | MEDLINE | ID: mdl-30213886

ABSTRACT

The Ugi reaction constructs α-acylaminoamide compounds by combining an aldehyde or ketone, an amine, a carboxylic acid, and an isocyanide in a single flask. Its appealing features include inherent atom and step economy together with the potential to generate products of broad structural diversity. However, control of the stereochemistry in this reaction has proven to be a formidable challenge. We describe an efficient enantioselective four-component Ugi reaction catalyzed by a chiral phosphoric acid derivative that delivers more than 80 α-acylaminoamides in good to excellent enantiomeric excess. Experimental and computational studies establish the reaction mechanism and origins of stereoselectivity.

18.
Chem Commun (Camb) ; 54(36): 4581-4584, 2018 May 01.
Article in English | MEDLINE | ID: mdl-29667658

ABSTRACT

Although recent progress has been made in introducing an SCF3 functionality into a variety of molecules, enantioselective trifluoromethylthiolation remains challenging, especially the α-trifluoromethylthiolation of carbonyl compounds. The present study describes a diastereo and enantioselective Cu-catalyzed tandem 1,4-addition/trifluoromethylthiolation of acyclic enones. The tandem reaction enables the asymmetric integration of the -SCF3 group to carbonyl compounds, establishing chiral tertiary α-carbon centers and affording α-SCF3-ß-substituted carbonyl compounds in 50-92% yields with up to 20 : 1 dr and 96% ee.

19.
Chem Commun (Camb) ; 53(51): 6844-6847, 2017 Jun 22.
Article in English | MEDLINE | ID: mdl-28603797

ABSTRACT

The chromanone scaffold is a privileged structure in heterocyclic chemistry and drug discovery. A highly efficient copper-catalyzed asymmetric conjugated reduction of chromones is developed to give chiral chromanones with good yields (80-99%) and excellent ee values (94->99% ee). Particularly noteworthy is that chiral thiochromanones are also constructed using this method in 74-87% yields with 96-97% ee. The established asymmetric synthesis paves the way for their further pharmaceutical studies.

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