Synthesis of P‐Stereogenic Compounds by Transition Metal‐Catalyzed Asymmetric Transformation of H−P(O) Compounds: Progress, Challenges, and Prospects DOI

Kang Ding,

Bo Su

European Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 27(4)

Published: Dec. 5, 2023

Abstract The synthesis of P‐stereogenic phosphorus compounds has gained considerable attention due to their wide applications across many research fields. Among the available strategies, transition metal‐catalyzed asymmetric transformation pentavalent phosphoryl (H−P(O)) precursors is particularly appealing. This approach involves a direct C−P bond‐forming process, rendering it straightforward, and employs readily available, bench‐stable H−P(O) reagents that are compatible with various metal catalysts. Recent years have witnessed significant progress in this field, primary focus on cross‐couplings hydrophosphorylations. Concept article provides brief summary recent progress, highlights existing challenges, discusses future directions exciting area.

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

76
Copper‐Catalyzed Dynamic Kinetic Asymmetric P−C Coupling of Secondary Phosphine Oxides and Aryl Iodides DOI

Jie Kang,

Kang Ding,

Si‐Mu Ren

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(25)

Published: April 14, 2023

Abstract Transition‐metal‐catalyzed enantioselective P−C cross‐coupling of secondary phosphine oxides (SPOs) is an attractive method for synthesizing P ‐stereogenic phosphorus compounds, but the development such a dynamic kinetic asymmetric process remains considerable challenge. Here we report unprecedented highly intermolecular coupling SPOs and aryl iodides catalyzed by copper complexes ligated finely modified chiral 1,2‐diamine ligand. The reaction tolerates wide range iodides, affording tertiary (TPOs) in high yields with good enantioselectivity (average 89.2 % ee). resulting enantioenriched TPOs were transformed into structurally diverse ‐chiral scaffolds, which are valuable as ligands catalysts synthesis.

Language: Английский

Citations

33
Palladium‐Catalyzed Enantio‐ and Regioselective Ring‐Opening Hydrophosphinylation of Methylenecyclopropanes DOI Creative Commons
Jian Zhou, Ling Meng, Shujuan Lin

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(26)

Published: April 26, 2023

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

Language: Английский

Citations

32
Synthesis of P‐Stereogenic Phosphine Oxides via Nickel‐Catalyzed Asymmetric Cross‐Coupling of Secondary Phosphine Oxides with Alkenyl and Aryl Bromides DOI Open Access
Chuanyong Wang,

Xiaobo Hu,

Cheng Xu

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(15)

Published: Feb. 14, 2023

Abstract A general and mild nickel‐catalyzed enantioselective C(sp 2 )−P cross‐coupling for synthesizing P‐stereogenic phosphine oxides has been developed. The asymmetric alkenylation/arylation of racemic secondary with alkenyl/aryl bromides generated high yields enantioselectivities. Various functional groups were tolerated, the applications this method demonstrated through late‐stage functionalization product transformations.

Language: Английский

Citations

31
Catalytic Asymmetric Hydrophosphinylation of 2‐Vinylazaarenes to Access P‐Chiral 2‐Azaaryl‐Ethylphosphine Oxides DOI
Binghui Wang, Yilin Liu,

Chenyang Jiang

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(16)

Published: Feb. 22, 2023

A chiral Brønsted acid-catalysed asymmetric hydrophosphinylation of 2-vinylazaarenes by secondary phosphine oxides is described. variety P-chiral 2-azaaryl-ethylphosphine are synthesized with high yields and ees, which both the substituents phosphines azaarenes can be flexibly modulated, underscoring an exceptionally broad scope substrates. These adducts valuable to metal catalysis since resultant tertiary from reduction them verified as a kind effective C1 -symmetric 1,5-hybrid P,N-ligands. Importantly, this platform enables generic efficient kinetic resolution oxides. It thus provides expedient approach access enantiomers derived hydrophosphinylation, further improving utility method.

Language: Английский

Citations

29
NiII-Catalyzed Enantioselective Anti-Markovnikov Hydrophosphination of Unactivated Alkynes DOI

Wei-Han Wang,

Yue Wu,

Peng-Jia Qi

et al.

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(10), P. 6994 - 7001

Published: May 9, 2023

A mechanism-inspired, reaction mode-controlled enantio- and regioselective anti-Markovnikov hydrophosphination of unactivated alkynes was accomplished by NiII catalysis. Alkenyl phosphine products could be obtained with high regio- enantioselectivity easily derivatized to structurally diverse chiral compounds. Mechanistic studies on both Ni0-catalyzed Markovnikov addition NiII-catalyzed have been carried out combining experimental computational methods. In the Ni0 system, an allyl nickel complex as catalyst resting state whose structure unambiguously determined single-crystal XRD analysis. sequential hydrometallation, ligand exchange, reductive elimination mechanism elucidated corroboratively DFT calculations. cationic secondary serves active catalyst. migratory insertion protonation sequence operative accomplish hydrophosphination.

Language: Английский

Citations

26
Nickel-catalysed enantioselective hydrosulfenation of alkynes DOI

Y.Z. Zhang,

Lingfei Hu,

Liyan Yuwen

et al.

Nature Catalysis, Journal Year: 2023, Volume and Issue: 6(6), P. 487 - 494

Published: June 12, 2023

Language: Английский

Citations

26
Visible-Light-Induced Regioselective Radical-Polar Crossover 1,4-Hydrophosphinylation of 1,3-Enynes: Access to Trisubstituted Allenes Bearing a Phosphine Oxide Group DOI

Qingzhi Cao,

Miaomiao Li, Xu-Dong Mao

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(22), P. 4678 - 4683

Published: May 24, 2024

The radical 1,4-functionalizations of 1,3-enynes have emerged as a powerful strategy for the synthesis multisubstituted allenes. However, phosphorus-centered radical-initiated transformations remain largely elusive. Herein, visible-light photoredox catalytic regioselective hydrophosphinylation with diaryl phosphine oxides phosphinoyl precursors has been realized. This protocol features mild conditions, wide substrate scope, and good functional group tolerance, producing diverse range phosphinoyl-substituted allenes in moderate to yields high atom economy. Detailed mechanistic experiments revealed radical-polar crossover process reaction.

Language: Английский

Citations

10
Catalytic Enantioselective Nucleophilic Desymmetrization at Phosphorus(V): A Three-Phase Strategy for Modular Preparation of Phosphoramidates DOI

Xiao‐kang Nie,

Shiqi Zhang, Xuyang Wang

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

Chiral phosphoramidates characterized by at least a P–N bond without P–C demonstrate significant applicative value within nucleoside phosphoramidate prodrugs. Despite the availability of methodologies for selective construction diverse chiral organophosphorus entities, achieving P-stereocenters solely substituted heteroatoms often relies on diastereomeric synthesis. Here, we present catalytic enantioselective desymmetrization strategy using an electrophilic phosphorus reagent with three leaving groups as substrate, enabling three-phase nucleophilic attack various alcohols and amines. By generating broad range possible substituent combinations around atoms, this synthetic may expedite synthesis screening biologically active phosphoramidates.

Language: Английский

Citations

1
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

Citations

6