P-Stereogenic Phosphorus Ligands in Asymmetric Catalysis

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(14), P. 8657 - 8739

Published: July 2, 2024

Chiral phosphorus ligands play a crucial role in asymmetric catalysis for the efficient synthesis of useful optically active compounds. They are largely categorized into two classes: backbone chirality and P-stereogenic ligands. Most reported belong to former class. Privileged ones such as BINAP DuPhos frequently employed wide range catalytic transformations. In contrast, latter class has remained small family many years mainly because their synthetic difficulty. The late 1990s saw emergence novel with superior enantioinduction ability Rh-catalyzed hydrogenation reactions. Since then, numerous have been synthesized used This Review summarizes thus far, including stereochemical electronic properties that afford high excellent enantioselectivities. Examples reactions use this described together applications construction key intermediates natural products therapeutic agents. literature covered dates back 1968 up until December 2023, centering on studies published later years.

Language: Английский

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Applying statistical modeling strategies to sparse datasets in synthetic chemistry

Science Advances, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 1, 2025

The application of statistical modeling in organic chemistry is emerging as a standard practice for probing structure-activity relationships and predictive tool many optimization objectives. This review aimed tutorial those entering the area chemistry. We provide case studies to highlight considerations approaches that can be used successfully analyze datasets low data regimes, common situation encountered given experimental demands Statistical hinges on (what being modeled), descriptors (how are represented), algorithms modeled). Herein, we focus how various reaction outputs (e.g., yield, rate, selectivity, solubility, stability, turnover number) structures binned, heavily skewed, distributed) influence choice algorithm constructing chemically insightful models.

Language: Английский

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Oxidative Dearomatization of Pyridines

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(4), P. 2358 - 2363

Published: Jan. 17, 2024

Dearomatization of pyridines is a well-established synthetic approach to access piperidines. Although remarkably powerful, existing dearomatization processes have been limited the hydrogenation or addition carbon-based nucleophiles activated pyridiniums. Here, we show that arenophile-mediated dearomatizations can be applied directly introduce heteroatom functionalities without prior substrate activation. The arenophile platform in combination with olefin oxidation chemistry provides dihydropyridine cis-diols and epoxides. These previously elusive compounds are now readily accessible used for downstream preparation diversely functionalized

Language: Английский

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Predictive catalysis: a valuable step towards machine learning

Trends in Chemistry, Journal Year: 2023, Volume and Issue: 5(12), P. 935 - 946

Published: Nov. 18, 2023

Language: Английский

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2,3‐Bis[( R )‐(1,1‐dimethylethyl)methylphosphino]‐Quinoxaline

Encyclopedia of Reagents for Organic Synthesis, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 9

Published: Jan. 3, 2025

Abstract image [ 866081‐62‐1 ] C 18 H 28 N 2 P (MW 334.38) InChI = 1S/C18H28N2P2/c1‐17(2,3)21(7)15‐16(22(8)18(4,5)6)20‐14‐12‐10‐9‐11‐13(14)19‐15/h9‐12H,1‐8H3/t21‐,22‐/m0/s1 InChIKey DRZBLHZZDMCPGX‐VXKWHMMOSA‐N (reagent may be used as a chiral ligand for rhodium, palladium, copper, and silver complexes to perform enantioselective reductions, conjugate additions, allylic alkylations) Alternate Name: QuinoxP*. Physical Data: mp 102–103°C; [α] D −54.3° ( c 1.00, CHCl 3 ); 1 NMR (395.75 MHz, CDCl ) δ 1.00–1.03 (m, ), 1.42–1.44 6 7.70–7.74 8.08–8.12 13 (99.45 4.77 (t, J 4.1 Hz), 27.59 7.4 31.90 129.50, 129.60, 141.63, 165.12 (dd, 5.7, 2.4 Hz); 31 (202.35 δ−17.7 (s); IR (KBr) 2950, 1470, 780 cm −1 ; HRMS (FAB) calcd. 29 (M + H); 335.1809; found: 335.1826. Anal. : C, 64.66; H, 8.44. Found: 64.57; 8.29. Solubility: sol toluene, ether, THF, dichloromethane, hexane. Form Supplied in: orange solid; commercially available. Preparative Methods: solution of n ‐BuLi (1.25 mL 1.60 M hexane solution, 2.0 mmol) was added dropwise stirred t ‐butylmethylphosphine–borane (236 mg, in THF (4 mL) at −78 °C under nitrogen. After 15 min, 2,3‐dichloroquinoxaline (133 0.67 one portion with vigorous stirring the mixture warmed rt during h. additional h, tetramethylethylenediamine (1 continued The reaction quenched HCl extracted combined extracts were washed brine, dried over Na SO 4 . solvent removed vacuum residue purified by chromatography on silica gel (hexane/EtOAc 30/1) give desired product (179 8%) an solid, which further recrystallization from hot MeOH (1.7 cubes. Handling, Storage, Precautions stable air moisture more than 8 months.

Language: Английский

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Enantioselective Copper-Catalyzed Three-Component Cascade Boronation–Dearomatization Reaction: Synthesis of Chiral Boron-Containing 1,4-Dihydropyridines

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

A three-component cascade boronation–dearomatization reaction of alkenes, a diboron compound, and pyridinium salt is diclosed, affording chiral boron-containing 1,4-dihyropyridines in high yields (≤98%) diastereoselectivity (≤10:1 dr), along with excellent enantioselectivity (typically >99% ee). The catalytic system performs efficiently at low catalyst loadings (1 mol %) was tested >50 examples, including some biologically active molecules.

Language: Английский

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Reimagining Dearomatization: Arenophile-Mediated Single-Atom Insertions and π-Extensions

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

ConspectusDearomatization of simple aromatics serves as one the most direct strategies for converting abundant chemical feedstocks into three-dimensional value-added products. Among such transformations, cycloadditions between arenes and alkenes have historically offered effective means to construct complex polycyclic architectures. However, traditionally harsh conditions, high-energy UV light irradiation, greatly limited scope this transformation. Nevertheless, recent progress has led development visible-light-promoted dearomative photocycloadditions with expanded capable preparing bicyclic structures.A fundamentally distinct approach involves visible-light activation arenophiles, which undergo para-photocycloaddition various aromatic compounds produce arene-arenophile cycloadducts. While only transiently stable subject retro-cycloaddition, further functionalization photocycloadducts allowed a wide collection dearomatization methodologies that access products orthogonal existing biological processes. Central strategy was observation photocycloaddition reveals π-system can be functionalized through traditional olefin chemistry. Coupled subsequent [4 + 2]-cycloreversion arenophile, process acts effectively isolate single from an ring. We developed several transformations bias methodology perform single-atom insertion π-extension reactions prepare unique cannot prepared easily means.Through application epoxidation, we were able develop method epoxidation pyridines arene-oxides pyridine-oxides, respectively. Notably, when arenophile chemistry is applied arenes, transposed site native olefinic reactivity, enabling site-selectivity functionalization. As result, oxygen (aza)arenes 3-benzoxepines. When applying in context cyclopropanations, accomplish cyclopropanation yield benzocycloheptatrienes upon cycloreversion. while Buchner ring expansion powerful carbon corresponding does not ring-expanded Furthermore, could utilized synthesis novel nanographenes M-region annulative (M-APEX) reaction. Traditionally, methods rely on reactivity at K- bay-region. arenophiles activate reactivity. arenophile-mediated diarylation, followed by cycloreversion, deliver π-extended exclusive selectivity.

Language: Английский

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Visible-light-induced meta-selective sulfonylation of pyridine via an EDA complex

Chemical Communications, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Pyridine is a versatile structural unit found in broad spectrum of pharmaceuticals, agrochemicals, and materials. Achieving selective meta-functionalization under mild conditions remains challenging due to its inherent electronic properties. In this work, we accomplished photoinduced method for meta-selective sulfonylation pyridines, facilitated by an electron donor-acceptor (EDA) complex between iodide ions sulfonyl chlorides. The reaction proceeds via oxazino-pyridine intermediate, with chloride acting as the radical precursor. This protocol stands out mild, photocatalyst-free conditions, high C5-selectivity, good scalability, offering promising approach synthesis meta-sulfonylated pyridines.

Language: Английский

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α-(N-Alkyl-N-heteroarenium)-α-diazoacetates: synthesis and reactivity of a novel class of ‘onium’ diazo compounds

Organic & Biomolecular Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Unprecedented diazoacetate N -heteroarenium salts are synthesized and participate in catalytic [2 + 1] cycloadditions [2,3]-sigmatropic rearrangements, providing facile access to otherwise difficult-to-obtain multi-functionalized -heterocycles.

Language: Английский

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Enantio‐ and Regioselective Copper‐Catalyzed 1,2‐Dearomatization of Pyridines

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(48)

Published: Oct. 11, 2023

A copper-catalyzed dearomative alkynylation of pyridines is reported with excellent regio- and enantioselectivities. The synthetically valuable enantioenriched 2-alkynyl-1,2-dihydropyridine products afforded are generated from the readily available feedstock, pyridine, commercially terminal alkynes. three-component reaction between a alkyne, methyl chloroformate employs copper chloride StackPhos, chiral biaryl P,N- ligand, as catalytic system. Under mild conditions, desired 1,2-addition delivered in up to 99 % yield regioselectivity ratios 25 : 1 enantioselectivities values ee. Activated non-activated alkynes containing wide range functional groups well tolerated. Even acetylene gas mono-alkynylated high Application methodology an efficient enantioselective synthesis piperidine indolizidine, coniceine, reported.

Language: Английский

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