Intermolecular Buchwald–Hartwig Reactions for Enantioselective Synthesis of Diverse Atropisomers: Rerouting the C–N Forming Mechanism to Substrate Oxygen-Assisted Reductive Elimination

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(24), С. 16567 - 16580

Опубликована: Июнь 7, 2024

Axially chiral biaryls featuring a C–N axis are important functional molecules in diverse fields. The asymmetric Buchwald–Hartwig reaction represents powerful strategy for these targets. Previous studies, however, have been predominantly restricted to intramolecular atroposelective coupling, likely due the steric and entropic effects reductive elimination of Pd(II) species with sterically congested aryl nitrogen groups. We now report two intermolecular coupling systems bulky NH lactams halohydrocarbons enabled by rerouting mechanism one that accommodates challenging substrates. Both exhibited group tolerance, excellent enantioselectivity, high Z selectivity (if applicable), affording atropisomeric biaryl olefins through de novo construction axis. Experimental computational studies were performed elucidate mechanism, switch pathways is traced effect (ortho substituent) halide substrate. A 2,6-disubstituted reorients proximal lactamide ligand its unusual O-ligation mode. With amide oxygen participation, this intermediate undergoes an accessible barrier five-membered ring transition state, pathway as well induction mode has much underexplored catalysis.

Язык: Английский

---

A General Amino–(Hetero)arylation of Simple Olefins with (Hetero)aryl Sulfonamides Enabled by an N-Triazinyl Group

ACS Catalysis, Год журнала: 2025, Номер 15(3), С. 2139 - 2149

Опубликована: Янв. 22, 2025

(Hetero)arylethylamines are privileged substructures in pharmaceuticals, agrochemicals, and other bioactive compounds. In principle, the amino–(hetero)arylation of olefins represents an ideal strategy for rapid preparation these pharmacophores, which could accelerate discovery valuable new products. Established methods, however, do not accommodate several important classes (hetero)aromatic structures, precludes access to appreciable range molecular architectures. To address limitations, we have developed a radical-mediated reaction that adds amino (hetero)aryl groups from simple stable sulfonamide across alkene. The identification readily available triazine as original N-protecting group was critical development this transformation. features good regio- stereoselectivity succeeds with medicinally unproductive alternate protocols. Lastly, highlighted advances by synthesizing TMP269, class IIa histone deacetylase inhibitor would otherwise be challenging prepare olefin amino–arylation.

Язык: Английский

---

Ni/Cu Cocatalyzed Asymmetric Hydrogenation of Amino Ketones with Water as a Hydrogen Source

ACS Catalysis, Год журнала: 2025, Номер unknown, С. 2666 - 2676

Опубликована: Янв. 29, 2025

Язык: Английский

---

Construction of axial and point chirality through Ni-catalyzed sila-cycloaddition reaction via desymmetrization and (dynamic) kinetic resolution

Science China Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 6, 2025

Язык: Английский

---

Half-Sandwich Ru(II) Complexes Featuring Metal-Centered Chirality: Configurational Stabilization by Ligand Design, Preparation via Kinetic Resolution, and Application in Asymmetric Catalysis

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Фев. 12, 2025

While it is well established that half-sandwich Ru(II) complexes possess metal-centered chirality, effective strategies to leverage their chirality toward asymmetric synthesis have been challenging due the configurational lability of metal stereocenters. The typically mediated by enantiopure ligands, which occupy a relatively narrow chemical space compared achiral counterparts. We demonstrate ligands can be used access chiral-at-ruthenium with exceptionally high stability. Key success introduction rigid bidentate ligand minimized dihedral angle between pyridyl and phenolic moieties, proved for preventing racemization. Computational studies revealed energetic factors contributing exceptional stability enabled planar structure successful design. These optically active incorporating aldehyde moieties were obtained NHC-catalyzed kinetic resolution excellent selectivities (s-factor up >200, ee 99%). further they are highly chiral catalysts 1,6-conjugate addition glycine ester para-quinone methide.

Язык: Английский

---

Enhanced Pyridine-Oxazoline Ligand-Enabled Pd(II)-Catalyzed Aminoacetoxylation of Alkenes for the Asymmetric Synthesis of Biaryl-Bridged 7-Membered N-Heterocycles and Atropisomers

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

A new class of binaphthyl unit-enhanced pyridine-oxazoline ligands was developed to promote the Pd-catalyzed enantioselective intramolecular 7-exo aminoacetoxylation unactivated biaryl alkenes. Biaryl-bridged 7-membered N-heterocycles bearing a chiral center were obtained in good yields with excellent enantioselectivities (up 99:1 er). Computational investigations on series biaryl-bridged rings provided insights into rotational barrier potentially unit by substituent effect including heteroatom, protecting group, and center. The kinetic resolution racemic axially biaryls via alkenes has also been achieved, affording previously inaccessible both axis, as well amino alcohols.

Язык: Английский

---

Rhodium(III)-Catalyzed Redox-Neutral [4 + 2] Annulation of 3,5-Diaryloxadiazoles with Alkynes: A Dual C–H Activation Strategy for Constructing C–N Atropisomers

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Апрель 22, 2025

A rhodium(III)-catalyzed dual-ring formation via cascade C-H activation/[4 + 2] annulation of 3,5-diaryoxadiazoles with alkynes was developed. This strategy has been demonstrated a variety 3,5-diaryloxadiazoles and alkynes, it successfully scaled up to gram-scale synthesis, highlighting its potential significance in the direct construction C-N atropisomers. Furthermore, cleavage N-O bond is essential for bicyclic structure absence an external oxidant. Mechanistic studies revealed that at 3-phenyl group oxadiazole likely rate-determining step this reaction.

Язык: Английский

---

Rhodium-catalyzed enantio- and diastereoselective carboamidation of bicyclic olefins toward construction of remote chiral centers and axis

Science China Chemistry, Год журнала: 2023, Номер 66(7), С. 2046 - 2052

Опубликована: Июнь 20, 2023

Язык: Английский

---

Access to distal biaxial atropisomers by iridium catalyzed asymmetric C–H alkylation

Chemical Science, Год журнала: 2024, Номер 15(33), С. 13541 - 13549

Опубликована: Янв. 1, 2024

Herein, we report an iridium-catalyzed asymmetric C–H activation combined with a desymmetrization strategy for synthesizing distal biaxial atropisomers excellent stereoselectivity, displaying promising photophysical and chiroptical properties.

Язык: Английский

---

Aryl Chloride-Directed Enantioselective C(sp²)-H Borylation Enabled by Iridium Catalysis

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(46), С. 25214 - 25221

Опубликована: Ноя. 7, 2023

We herein report the iridium-catalyzed enantioselective C-H borylation of aryl chlorides. A variety prochiral biaryl compounds could be well-tolerated, affording a vast array axially chiral biaryls with high enantioselectivities. The current method exhibits turnover number (TON) 7000, which represents highest in functional-group-directed asymmetric activation. TON was attributed to weak catalyst-substrate interaction that caused by mismatched chirality between catalyst and substrate. also demonstrated synthetic application C-B, ortho-C-H, C-Cl bond functionalization, including programmed Suzuki-Miyaura coupling for synthesis polyarenes.

Язык: Английский

---