Copper- and Palladium-Cocatalyzed Chemo-, Regio-, Stereo-, and Atroposelective Arylboration of 1,3-Enynes

ACS Catalysis, Год журнала: 2024, Номер 14(15), С. 11318 - 11331

Опубликована: Июль 15, 2024

Catalytic enantioselective borylation reactions of unsaturated bonds as powerful tools for the synthesis diverse chiral organoboron compounds have gained much attention and wide applications in various fields. However, atroposelective arylboration reaction with carbon–carbon triple 1,3-enynes to obtain axially 1,3-dienylboronates remains an elusive significant challenge. Hence, we develop a cooperative copper- palladium-catalyzed assemble plentiful function enriched single step from easily available 1,3-enynes, B2pin2, aryl bromides high levels chemo-, regio-, stereo-, atroposelectivity. The mild conditions lead good functional group tolerance, which is proven by broad substrate scope late-stage functionalizations bioactive or drug molecules. Moreover, can be scaled up, series further transformations achieved. It worth emphasizing that several olefin catalysts ligands axial chirality also synthesized through corresponding elaborations such products, explains transformative ability application potential 1,3-dienylboronates. mechanism experiment density theory (DFT) calculations revealed process copper palladium catalysis, indicating chemoselectivity regioselectivity boration are determined enyne insertion on copper, atroposelectivity controlled reductive elimination center. Meanwhile, calculation demonstrated distinct interactions between P═O C═O groups Pd Bpin center key transition state formation products varying configurations while employing identical configuration ligands.

Язык: Английский

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Rhodium(III)-Catalyzed Atroposelective Indolization to Access Planar-Chiral Macrocycles

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(42), С. 29214 - 29223

Опубликована: Окт. 9, 2024

Macrocycles incorporating conformationally defined indoles are widely found in bioactive natural products. However, the catalytic enantioselective synthesis of planar-chiral via indolization involving macrocyclization remains elusive. Herein, we present first rhodium(III)-catalyzed atroposelective macrocyclization, which involves C-H activation aniline, and a subsequent oxidation [3 + 2] annulation reaction with an intramolecular alkyne. This protocol achieves construction indoles, planar chirality control single step. Importantly, this strategy produces macrocyclic atropisomers bearing full-carbon ansa chains, represent challenging targets organic synthesis. Thermodynamic experiments revealed that rotational barrier chain-linked atropisomer was lower than oxa-ansa chain. The mechanism elucidated by computational studies, alkyne insertion steps collectively determined enantioselectivity.

Язык: Английский

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Divergent Synthesis of Axially Chiral 2-Pyranones and Fused 2-Pyridones via N-Heterocyclic Carbene-Catalyzed Atroposelective [3 + 3] Annulation

The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 24, 2025

An N-heterocyclic carbene-catalyzed atroposelective [3 + 3] annulation of alkynyl acylazoliums with benzothiazole derivatives has been developed for the divergent synthesis axially chiral triaryl 2-pyranones and fused 2-pyridones. The regioselectivity this protocol depends on structure benzothiazoles three different nucleophilic centers. obtained frameworks represent a new class arylheterocycle atropisomers, which may be potentially useful in medicinal chemistry.

Язык: Английский

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Palladium‐Catalyzed Enantioselective C−H Olefination to Access Planar‐Chiral Cyclophanes by Dynamic Kinetic Resolution

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(51)

Опубликована: Ноя. 3, 2023

Abstract Planar‐chiral cyclophanes have received increasing attention for drug discovery and catalyst design. However, the catalytically asymmetric synthesis of planar‐chiral has been a longstanding challenge. We describe first Pd(II)‐catalyzed enantioselective C−H olefination prochiral cyclophanes. The low rotational barrier less hindered benzene ring in substrates allows reaction to proceed through dynamic kinetic resolution. This approach exhibits broad substrate scope, providing high yields (up 99 %) with excellent enantioselectivities >99 % ee ). ansa chain length scope studies reveal that chirality arises from bond rotation constraint around macrocycle plane, rather than C−N axis. activation is also applicable late‐stage modification bioactive molecules pharmaceuticals.

Язык: Английский

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Highly Enantioselective Synthesis of Planar-Chiral Cyclophanes through a Brønsted Acid-Catalyzed Asymmetric Transfer Hydrogenation

ACS Catalysis, Год журнала: 2023, Номер 13(21), С. 14155 - 14162

Опубликована: Окт. 20, 2023

Planar-chiral cyclophanes have received increasing attention for drug discovery due to their unique properties arising from the conformational strain. However, catalytic asymmetric synthesis of planar-chiral is one long-standing challenges in chemistry. We herein report a Brønsted acid-catalyzed transfer hydrogenation (ATH) reaction cyclophane-derived imines, providing good yields (up 98%) and with high enantioselectivities >99% ee). The mutable ansa bridge allows ATH occur through kinetic resolution or dynamic process. [11]–[14]cyclophanes bearing an appropriate benzene ring substituent undergo KR process, while [15]–[17]cyclophanes DKR manner. Controlled experiments were performed understand mechanism origin enantioselectivity.

Язык: Английский

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Axially Chiral Cannabinoids: Design, Synthesis, and Cannabinoid Receptor Affinity

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(25), С. 13581 - 13591

Опубликована: Июнь 14, 2023

The resorcinol-terpene phytocannabinoid template is a privileged scaffold for the development of diverse therapeutics targeting endocannabinoid system. Axially chiral cannabinols (axCBNs) are unnatural (CBNs) that bear an additional C10 substituent, which twists cannabinol biaryl framework out planarity creating axis chirality. This unique structural modification hypothesized to enhance both physical and biological properties cannabinoid ligands, thus ushering in next generation system chemical probes cannabinoid-inspired leads drug development. In this full report, we describe philosophy guiding design axCBNs as well several synthetic strategies their construction. We also introduce second class axially cannabinoids inspired by cannabidiol (CBD), termed cannabidiols (axCBDs). Finally, provide analysis (axCannabinoid) atropisomerism, spans two classes (class 1 3 atropisomers), first evidence axCannabinoids retain─and some cases, strengthen─affinity functional activity at receptors. Together, these findings present promising new direction novel ligands discovery exploration complex

Язык: Английский

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Catalytic stereodivergent and simultaneous construction of axial and point chirality

Organic Chemistry Frontiers, Год журнала: 2024, Номер 11(12), С. 3308 - 3319

Опубликована: Янв. 1, 2024

An unprecedented ligand-enabled stereodivergent construction of both N–N axial and point chirality in a single step is reported.

Язык: Английский

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Catalytic asymmetric synthesis of sulfur-containing atropisomers by C-S bond formations

Science China Chemistry, Год журнала: 2023, Номер 66(12), С. 3331 - 3346

Опубликована: Ноя. 17, 2023

Язык: Английский

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An Approach for Highly Enantioselective Synthesis of meta-Disubstituted [n]Paracyclophanes

The Journal of Organic Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Сен. 27, 2024

Atroposelective synthesis of

Язык: Английский

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Isolable iminium ions as a platform for N-(hetero)aryl piperidine synthesis

Nature Synthesis, Год журнала: 2023, Номер 2(11), С. 1059 - 1067

Опубликована: Июнь 15, 2023

Язык: Английский

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