Rhodium-Catalyzed Homogeneous Asymmetric Hydrogenation of Naphthol Derivatives

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

Published: Jan. 29, 2025

Due to their strong aromaticity and difficulties in chemo-, regio-, enantioselectivity control, asymmetric hydrogenation of naphthol derivatives 1,2,3,4-tetrahydronaphthols has remained a long-standing challenge. Herein, we report the first example homogeneous catalyzed by tethered rhodium-diamine catalysts, affording wide array optically pure high yields with excellent enantioselectivities (up 98% yield >99% ee). Mechanistic studies experimental computational approaches reveal that fluorinated solvent 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) plays vital roles control reactivity selectivity, 1-naphthol is reduced via cascade reaction pathway, including dearomative tautomerization, 1,4-hydride addition, 1,2-hydride addition sequence. A novel synergistic activation mode was proposed which HFIP assists both hydrogen molecule presence base, situ-generated fleeting keto tautomer immediately trapped Rh(III)-H species before it escapes from cage. This protocol provides straightforward practical pathway for synthesis key intermediates several chiral drugs. Particularly, Nadolol, drug treatment hypertension, angina pectoris, congestive heart failure, certain arrhythmias, enantioselectively synthesized time.

Language: Английский

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Catalytic Asymmetric Transfer Hydrogenation of Acylboronates: BMIDA as the Privileged Directing Group

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(29), P. 20357 - 20369

Published: June 13, 2024

Developing a general, highly efficient, and enantioselective catalytic method for the synthesis of chiral alcohols is still formidable challenge. We report in this article asymmetric transfer hydrogenation (ATH) N-methyliminodiacetyl (MIDA) acylboronates as general substrate-independent entry to enantioenriched secondary alcohols. ATH acyl-MIDA-boronates with (het)aryl, alkyl, alkynyl, alkenyl, carbonyl substituents delivers variety α-boryl The latter are used range stereospecific transformations based on boron moiety, enabling carbinols two closely related α-substituents, which cannot be obtained high enantioselectivities using direct methods, such (R)-cloperastine intermediate. Computational studies illustrate that BMIDA group privileged enantioselectivity-directing Noyori–Ikariya compared conventionally aryl alkynyl groups due favorable CH–O attractive electrostatic interaction between η6-arene-CH catalyst σ-bonded oxygen atoms BMIDA. work expands domain conventional shows its huge potential addressing challenges symmetric synthesis.

Language: Английский

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Iridium-Catalyzed Asymmetric Hydrogenation of Unfunctionalized Cycloalkenes to Access Chiral 2-Aryl Tetralins

Organic Letters, Journal Year: 2024, Volume and Issue: 26(27), P. 5850 - 5855

Published: July 1, 2024

The transition-metal catalyzed asymmetric hydrogenation of unfunctionalized alkenes is challenging. Herein, we report an efficient iridium-catalyzed cycloalkenes, delivering chiral 2-aryl tetralins in excellent yields and with moderate to enantioselectivities. reaction can be performed on a gram-scale low catalyst loading (S/C = 1000), the reduced product was obtained without erosion enantioselectivity. Deuterium experiments indicated that C═C bond substrate hydrogenated directly isomerization.

Language: Английский

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Catalytic Asymmetric Transfer Hydrogenation of β,γ-Unsaturated α-Diketones

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 27, 2024

Asymmetric transfer hydrogenation (ATH) has been recognized as a highly valuable strategy that allows access to enantioenriched substances and widely applied in the industrial production of drug molecules. However, despite great success ATH ketones, efficient, regio- stereoselective on enones remains underdeveloped. Moreover, optically pure acyloins 1,2-diols are both extremely useful building blocks organic synthesis, medicinal chemistry, materials science, but concise asymmetric approaches allowing different types have scarcely discovered. We report this paper first efficient readily accessible β,γ-unsaturated α-diketones. The protocol affords four fashion. synthetic value work showcased by divergent synthesis related natural products. systematic mechanistic studies density functional theory (DFT) calculations illustrated origin reactivity divergence, revealed roles aromatic aliphatic substituents substrates, provided range unique rationales not disclosed ATH-related studies.

Language: Английский

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Enantioselective Synthesis of Chiral β²-Amino Phosphorus Derivatives via Nickel-Catalyzed Asymmetric Hydrogenation

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 27, 2024

Compared with chiral β3-amino phosphorus compounds, which can be easily derived from natural optically pure α-amino acids, obtaining β2-amino derivatives remains a challenge. These derivatives, cannot amino possess unique biological activities or potential catalytic activities. Herein, highly enantioselective hydrogenation for the preparation of E-β-enamido compounds is reported by using green and low-cost earth-abundant metal nickel catalyst (13 examples 99% ee). In particular, this system provides same enantiomer product E- Z-alkene substrates, E/Z-substrate mixtures provide good results (up to 96% The products diversely derivatized, exhibit as novel β2-aminophosphine ligands. Density functional theory calculations reveal that weak attractive interactions between substrate are crucial achieving perfect enantioselectivities. addition, different coordination modes Z-substrates may result in formation product.

Language: Английский

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Asymmetric Transfer Hydrogenation of Stable NH Imines for the Synthesis of Enantiopure α‐Chiral Primary Amines

Chinese Journal of Chemistry, Journal Year: 2024, Volume and Issue: 42(18), P. 2211 - 2216

Published: May 14, 2024

Comprehensive Summary Although it offers a direct route to access synthetically valuable α‐chiral primary amines, asymmetric transfer hydrogenation of NH imines has been rarely studied, due in large part the inaccessibility and instability imines. Herein, we report Rh‐catalyzed kind novel stable which are prepared via condensation easily available sulfonylated 2’‐aminoacetophenones with 3 methanol. With this method, enantioenriched chiral 2‐(1‐aminoalkyl)anilines, privileged pharmacore groups, have synthesized good functional group compatibility, up 99% ee. A gram‐scale reaction using 0.2 mol% catalyst successfully performed highlight practicality. Furthermore, products can be derivatized into enantiopure bioactive molecules as well tridentate ligands for metal catalysis.

Language: Английский

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Rhodium-Catalyzed Asymmetric Hydrogenation and Transfer Hydrogenation of α-Nitro Ketones

Organic Letters, Journal Year: 2024, Volume and Issue: 26(46), P. 10008 - 10012

Published: Nov. 13, 2024

A catalytic protocol for the enantioselective hydrogenation and transfer of α-nitro ketones was developed, providing a wide range β-nitro-α-phenylethanols with high yields excellent enantioselectivities (up to 98% yield up >99.9% ee). Compatibility solvents bases demonstrates robustness this reaction. The synthetic potential demonstrated by TON experiment as well application in synthesis key intermediates mirabegron (S/C = 10,000, 95% yield, 99%

Language: Английский

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Supramolecular bidentate rhodium(I) or iridium(I) phosphine and oxazoline amino acid bioconjugates as selective catalysts for enantioselective reactions

Dalton Transactions, Journal Year: 2024, Volume and Issue: 54(3), P. 1021 - 1037

Published: Nov. 15, 2024

Supramolecular Rh( i ) and Ir( catalysts were applied in enantioselective hydrogenation hydroformylation. The presence of a heteroleptic rhodium precatalytic complex with bioconjugate ligands, SupraPHOX, has been confirmed spectroscopically.

Language: Английский

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Ruthenium-Catalyzed Formal Asymmetric Reductive Isomerization of α-Hydroxyenones

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(24), P. 18753 - 18764

Published: Dec. 10, 2024

The isomerization of α-hydroxyketones (acyloins) is a fundamental transformation in carbohydrate chemistry. It has been found to play important roles the metabolic processes living organisms and organic synthesis. However, catalytic asymmetric acyloin remains formidable challenge not addressed. In this work, we report unprecedented ruthenium-catalyzed formal reductive α-hydroxyenones. protocol affords variety enantioenriched acyloins with high level enantioselectivities, systematic mechanistic studies demonstrate involving α-hydroxyenones transfer hydrogenation. work provides an alternative approach realizing challenging isomerization.

Language: Английский

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