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

Shuai-Shuai Fang,

Xin Hu,

Ming‐Hong Li

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(45), P. 31339 - 31347

Published: Nov. 4, 2024

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, remdesivir. The stereochemical configuration at the phosphorus center ProTides significantly influences their pharmacological properties, necessitating efficient stereoselective synthesis. Traditional methods using chiral auxiliaries or nonracemic phosphorylating agents are labor-intensive inefficient, while recent organocatalytic approaches, despite promise, still face limitations. Herein, we present novel approach employing metal complexes for assembly P-stereogenic via asymmetric P-O bond formation. This leverages catalyst activate electrophilic reagent, facilitating base-promoted nucleophilic replacement pathway. Our protocol, featuring mild reaction conditions broad applicability, enables highly synthesis previously inaccessible (

Language: Английский

Palladium-catalyzed asymmetric hydrophosphination of internal alkynes: Atroposelective access to phosphine-functionalized olefins DOI Creative Commons

Danqing Ji,

Jierui Jing,

Yi Wang

et al.

Chem, Journal Year: 2022, Volume and Issue: 8(12), P. 3346 - 3362

Published: Sept. 23, 2022

Language: Английский

Citations

79
Cobalt‐Catalysed Asymmetric Addition and Alkylation of Secondary Phosphine Oxides for the Synthesis of P‐Stereogenic Compounds DOI

Zeng‐Hua Wu,

An‐Qi Cheng,

Yuan Meng

et al.

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(52), P. 27241 - 27246

Published: Nov. 5, 2021

The catalytic asymmetric synthesis of P-chiral phosphorus compounds is an important way to construct ligands. Herein, we report a new strategy that adopts the pyridinyl moiety as coordinating group in cobalt-catalysed nucleophilic addition/alkylation secondary phosphine oxides. A series tertiary oxides were generated with up 99 % yield and 99.5 ee, broad functional-group tolerance. Mechanistic studies reveal (R)-secondary preferentially interact cobalt catalysts produce P-stereogenic compounds.

Language: Английский

Citations

79
Palladium/Xiao‐Phos‐Catalyzed Kinetic Resolution of sec‐Phosphine Oxides by P‐Benzylation DOI
Qiang Dai, Lu Liu, Junliang Zhang

et al.

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(52), P. 27247 - 27252

Published: Oct. 21, 2021

P-stereogenic tert- and sec-phosphines have wide applications in asymmetric catalysis, materials, pharmaceutical chemistry, however, their practical synthesis still constitutes a significant challenge. Herein, successful kinetic resolution of rac-secondary phosphine oxides via the enantioselective P-benzylation process catalyzed by palladium/Xiao-Phos was designed. Both sec-phosphine were delivered good yield excellent enantiopurity (selectivity factor up to 226.1). The appealing synthetic utilities are further demonstrated facile preparation several valuable P-chiral compounds, precursors bidentate ligands, as well transition metal complexes.

Language: Английский

Citations

78
Enantioselective Palladium‐Catalyzed Hydrophosphinylation of Allenes with Phosphine Oxides: Access to Chiral Allylic Phosphine Oxides DOI
Zhiping Yang, Jun Wang

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(52), P. 27288 - 27292

Published: Sept. 28, 2021

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

Language: Английский

Citations

77
Catalytic Asymmetric Axially Chiral Allenyl C–P Bond Formation DOI
Huanan Wang, Hui Qian, Junliang Zhang

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(28), P. 12619 - 12626

Published: July 8, 2022

Chiral organophosphorous compounds are very important in catalysis, organic syntheses, and medicinal chemistry. However, catalytic enantioselective protocols for the axially chiral allenyl phosphorus have never been reported. Herein, a palladium-catalyzed carbon–phosphorus bond formation reaction affording phosphonates has developed. The enjoys high yields ees accommodating wide range of functional groups. Mechanistic studies unveiled an overwhelming kinetic resolution process.

Language: Английский

Citations

55
Ni-catalyzed asymmetric hydrophosphinylation of conjugated enynes and mechanistic studies DOI Creative Commons
Yaqian Zhang,

Xue-Yu Han,

Yue Wu

et al.

Chemical Science, Journal Year: 2022, Volume and Issue: 13(14), P. 4095 - 4102

Published: Jan. 1, 2022

The catalytic asymmetric synthesis of

Language: Английский

Citations

54
Rh-Catalyzed Regio- and Enantioselective Allylic Phosphinylation DOI
Bing Li, Min Liu, Sajid Ur Rehman

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(7), P. 2893 - 2898

Published: Feb. 14, 2022

Transition-metal-catalyzed branched and enantioselective allylic substitution of monosubstituted precursors with carbon, nitrogen, oxygen, sulfur, fluoride nucleophiles has been well-established. However, such a selective carbon–phosphorus bond formation not realized probably due to the catalyst deactivation by strong coordinating nature phosphinylating reagents. Herein, we report Rh-catalyzed highly regio- synthesis phosphine oxides in presence chiral bisoxazoline-phosphine ligand. The application α-hydroxylalkylphosphine keep low concentration secondary is essential for high yields. addition diphenyl phosphoric acid was found only activate alcohols but also accelerate formation.

Language: Английский

Citations

52
Copper‐Catalyzed Dynamic Kinetic C−P Cross‐Coupling/Cyclization for the Concise Asymmetric Synthesis of Six‐, Seven‐ and Eight‐MemberedP‐Stereogenic Phosphorus Heterocycles DOI
Yanli Li, Xiao Jin, Peng Liu

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(24)

Published: March 29, 2022

Abstract A copper‐catalyzed asymmetric aryl C−P cross‐coupling/cyclization reaction was successfully developed via dynamic kinetic transformation (DYKAT) under mild conditions. This study provides a general and simple method for the catalytic enantioselective synthesis of stable six‐, seven‐ eight‐membered P‐stereogenic phosphorus heterocycles with excellent enantioselectivities moderate to high yields. One‐pot gram‐scale P‐heterocycle from commercially available materials also accomplished enantioselectivity yield.

Language: Английский

Citations

46
Ni-Catalyzed Enantioselective Benzylation of Secondary Phosphine Oxide DOI

Wen-Qiang Cai,

Wei Qi, Qing‐Wei Zhang

et al.

Organic Letters, Journal Year: 2022, Volume and Issue: 24(5), P. 1258 - 1262

Published: Feb. 2, 2022

A nickel-catalyzed benzylic substitution of secondary phosphine oxide was described, affording the dialkylated P-stereogenic tertiary oxides with high to excellent enantioselectivities. The reaction performed under mild conditions commercially available benzyl chlorides and bench stable oxides, exhibiting broad functional group tolerance. It represented a practical example for preparation compounds.

Language: Английский

Citations

43
Bulky P-stereogenic ligands. A success story in asymmetric catalysis DOI Creative Commons
Pep Rojo, Antoni Riéra, Xavier Verdaguer

et al.

Coordination Chemistry Reviews, Journal Year: 2023, Volume and Issue: 489, P. 215192 - 215192

Published: May 9, 2023

Since the development of BisP* ligand by Imamoto, P-stereogenic phosphines bearing a bulky tert-butyl group and smaller alkyl have demonstrated extraordinary proficiency in wide range asymmetric processes. Over time, this class ligands has brought about introduction more rigid backbones, three-hindered quadrant concept, substitution adamantyl. The methyl fragment also been introduced phosphino-oxazoline-type ligands, chemists industrial sector contributed to evolution reporting first successful Buchwald-type monophosphines for coupling reactions. present review covers synthesis applications that developed since advent late 1990s, with special emphasis on successfully applied catalysis.

Language: Английский

Citations

37