A modular approach to catalytic stereoselective synthesis of chiral 1,2-diols and 1,3-diols

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 3, 2025

Optically pure 1,2-diols and 1,3-diols are the most privileged structural motifs, widely present in natural products, pharmaceuticals chiral auxiliaries or ligands. However, their synthesis relies on use of toxic expensive metal catalysts suffer from low regioselectivity. Catalytic asymmetric optically 1,n-diols bulk chemicals a highly stereoselective atom-economical manner remains formidable challenge. Here, we disclose versatile modular method for enantioenriched high-production-volume ethane-1,2-diol (MEG) 1,3-propanediol (PDO), respectively. The key to success is temporarily mask diol group as an acetonide, which imparts selectivity step C(sp3)-H functionalization. Additionally, containing two stereogenic centers also prepared through diastereoselective late-stage functionalization biological active compounds expedient ligands pharmaceutically relevant molecules further highlight synthetic potential this protocol. authors report ethylene glycol 1,3-propanediol,

Язык: Английский

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Thermal Nickel-Catalyzed Carbon–Oxygen Cross-Coupling of (Hetero)aryl Halides with Alcohols Enabled by the Use of a Silane Reductant Approach

ACS Catalysis, Год журнала: 2024, Номер 14(10), С. 7846 - 7852

Опубликована: Май 6, 2024

Herein, we disclose a highly efficient thermal Ni-catalyzed C–O cross-coupling of aryl halides with primary and secondary alcohols, without the need for photo- or electrocatalysis. The protocol is simple has wide substrate scope, particularly challenging electron-rich halides. Additionally, this methodology been successfully applied to late-stage functionalization drugs natural products, as well synthesis pharmaceuticals such pramoxine delamanid key intermediate. Preliminary mechanistic studies suggest in situ generation active Ni(I) species from inexpensive NiBr2-bipyridine PhSiH3.

Язык: Английский

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DalPhos on Demand: Facile Ligand Generation Enables New Ligand Discovery and Expedient Catalyst Screening

ACS Catalysis, Год журнала: 2024, Номер 14(6), С. 4074 - 4081

Опубликована: Фев. 29, 2024

DalPhos/Ni-based catalysts have emerged as top performers in C–N and C–O cross-couplings. Expedient means of generating such ligands would facilitate the discovery effective DalPhos ligand variants well accelerate reaction development processes for end users. A protocol structurally varied phosphine- phosphonite-type from a single precursor upon treatment with commercial reagents without need chromatographic purification is disclosed. The formation via this divergent synthetic strategy was exploited expedited screening representative Ni-catalyzed cross-couplings, leading to identification (i.e., BnPAd-DalPhos, L4, OAdPAd-DalPhos, L9) that, turn, were carried forward scope analysis challenging cross-couplings fluoroalkylamines, by use prepared (DalPhos)Ni(aryl)Cl precatalyst complexes. reported methodology offers user-friendly development.

Язык: Английский

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The Development of Cage Phosphine ‘DalPhos’ Ligands to Enable Nickel-Catalyzed Cross-Couplings of (Hetero)aryl Electrophiles

Chemical Science, Год журнала: 2024, Номер 15(20), С. 7394 - 7407

Опубликована: Янв. 1, 2024

The development of the DalPhos cage ligand family and application in developing state-of-the-art nickel-catalyzed cross-coupling chemistry is described.

Язык: Английский

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Intercepting Ketone α-Arylation Intermediates in the DalPhos/Ni-Catalyzed Synthesis of Decorated Benzofurans and NH-Indoles

ACS Catalysis, Год журнала: 2025, Номер unknown, С. 3751 - 3767

Опубликована: Фев. 17, 2025

Язык: Английский

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Photoelectrochemistry-Promoted Ni-Catalyzed C–O Cross-Couplings

Precision Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 10, 2025

Язык: Английский

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Co‐Catalyzed Dehydrogenation Claisen Condensation of Secondary Alcohols with Esters^†

Chinese Journal of Chemistry, Год журнала: 2024, Номер 42(22), С. 2818 - 2824

Опубликована: Июль 17, 2024

Comprehensive Summary Catalytic dehydrogenation, with its exceptional atom economy and chemoselectivity, offers a highly desirable yet challenging approach for converting multiple environmentally friendly alcohols into crucial molecules. Furthermore, the utilization of catalysts based on abundant elements found Earth alcohol dehydrogenation to produce acryl ketone holds significant promise as versatile strategy in synthesizing key building blocks numerous pharmaceutical applications. The present study describes practical Co‐catalyzed cascade dehydrogenative Claisen condensation secondary esters, facilitating synthesis wide range 3‐hydroxy‐prop‐2‐en‐1‐ones. We introduce catalytic system novel scalable indazole NNP‐ligands coordinated cobalt efficient dehydrogenations alcohols, propose plausible reaction mechanism supported by control experiments labeling studies. Notably, it allows streamlined pharmaceuticals one‐pot.

Язык: Английский

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CuSO₄/N-(9H-carbazol-9-yl)picolinamide-Catalyzed C–O Coupling of (Hetero)Aryl Chlorides with Phenols on Water

Organic Letters, Год журнала: 2024, Номер 26(34), С. 7202 - 7206

Опубликована: Авг. 21, 2024

A Cu-catalyzed C–O coupling of (hetero)aryl chlorides with phenols at 120 °C on water was developed a designed ligand, N-(9H-carbazol-9-yl)picolinamide (L2). This method features good substrate scope (both electron-donating and electron-withdrawing), low catalyst/ligand loadings (down to 1 mol %), excellent scalability practicability.

Язык: Английский

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Synthesis of Hexafluoroisopropyl Aryl Ethers via Dual Photoredox/Nickel-Catalyzed C–O Coupling

Organic Letters, Год журнала: 2024, Номер 26(31), С. 6782 - 6786

Опубликована: Июль 31, 2024

Herein we report a photoredox/nickel-catalyzed cross-coupling of aryl bromides with 1,1,1,3,3,3-hexafluoroisopropanol for the construction hexafluoroisopropyl ethers. The mild reaction conditions employed allow applicability wide range and heteroaryl bromides. Late-stage functionalization preliminary mechanistic studies have been demonstrated.

Язык: Английский

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Scale-Up of Continuous Metallaphotoredox Catalyzed C–O Coupling to a 10 kg-Scale Using Small Footprint Photochemical Taylor Vortex Flow Reactors

Organic Process Research & Development, Год журнала: 2024, Номер 29(1), С. 34 - 47

Опубликована: Дек. 4, 2024

We report the development and optimization of a scalable flow process for metallaphotoredox (Ir/Ni) C-O coupling, mild efficient approach forming alkyl-aryl ethers, common motif in medicinal chemistry settings. Time-resolved infrared spectroscopy (TRIR) highlighted amine as major quencher photocatalyst triplet excited state, along with formation an Ir(II) species that, presence Ni cocatalyst, has its lifetime shortened, suggesting reductive quenching Ir(III)*, followed by reoxidation facilitated cocatalyst. TRIR batch reaction screening was used to develop conditions transferrable flow, many processing benefits performing were then demonstrated using simple construct/operate, small-footprint FEP coil reactor, including short (<10 min) space times reduced catalyst loadings (down 0.1 mol % Ir, 1 Ni) while retaining good yield/conversion. Scalability increasing length or diameter reactor tubing, however, due suspected mass transfer/mixing limitations, yield decreased upon scale-up some cases. Therefore, we applied modified version our previously reported photochemical Taylor Vortex Flow Reactor (PhotoVortex), where vortices short-irradiated path allow reactions be performed efficiently via excellent mixing. In small PhotoVortex (8 mL irradiated volume), have projected productivities around kg day-1 >10 large (185 volume) product yields (>90%) low (0.1 0.5 [Ir{dF(CF3)ppy}2dtbbpy]PF6), enabled mixing ensuring sufficient transfer between short-lived photoexcited other transient species.

Язык: Английский

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