A 13-million turnover-number anionic Ir-catalyst for a selective industrial route to chiral nicotine

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Июнь 22, 2023

Abstract Developing catalysts with both useful enantioselectivities and million turnover numbers (TONs) for asymmetric hydrogenation of ketones is attractive industrial production high-value bioactive chiral entities but remains a challenging. Herein , we report an ultra-efficient anionic Ir-catalyst integrated the concept multidentate ligation ketones. Biocatalysis-like efficacy up to 99% ee (enantiomeric excess), 13,425,000 TON (turnover number) 224 s −1 TOF frequency) were documented benchmark acetophenone. Up 1,000,000 achieved challenging pyridyl alkyl ketone where at most 10,000 TONs are previously reported. The showed novel preferred ONa/MH instead NNa/MH bifunctional mechanism. A selective route enantiopure nicotine has been established using this key step 500 kg batch scale, providing 40 tons scale product.

Язык: Английский

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Enantiodivergent Hydrogenation of Exocyclic α,β‐Unsaturated Lactams Enabled by Switching the N‐Chirality of Iridium Catalyst

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(11)

Опубликована: Янв. 11, 2023

Central chirality is an important chiral element used in the design of ligands and catalysts. Mostly, attention organic chemists focused on developing with stable stereogenic centers. However, N-chirality ligand has been rarely explored due to its flexibility. Here we demonstrate design, synthesis, application a class simple P,N-ligands flexible their derived iridium complexes fixed N-chiral stereocenters. Both configurations N-stereocenter could be selectively formed from same ligand. This pair diastereoisomeric showed good performance enantiodivergent asymmetric hydrogenation exocyclic α,β-unsaturated lactams. The N-H group plays impressive role catalytic activity. Computational studies emphasized importance group.

Язык: Английский

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Diastereoselective Hydrogenation of Tetrasubstituted Olefins using a Heterogeneous Pt‐Ni Alloy Catalyst

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(19)

Опубликована: Фев. 26, 2024

Abstract Stereoselective hydrogenation of tetrasubstituted olefins is an attractive method to access compounds with two contiguous stereocenters. However, homogeneous catalysts for enantio‐ and diastereoselective exhibit low reactivity toward due steric crowding between the ligand scaffold substrate. Monometallic heterogeneous catalysts, on other hand, provide accessible surface active sites hindered but unpredictable inconsistent stereoinduction. In this work, we develop a Pt−Ni bimetallic alloy catalyst that can diastereoselectively hydrogenate unactivated, sterically‐bulky olefins, utilizing more oxophilic Ni atoms adsorb hydroxyl directing group direct facially‐selective hydrogen addition olefin via Pt atoms. Structure‐activity studies several compositions underscore importance exposing uniform PtNi achieve high diastereoselectivity minimize side reactions. The optimized Pt−Ni/SiO 2 exhibits good functional tolerance broad scope in cyclopentene scaffold, generating cyclopentanol products three synthetic utility demonstrated four‐step synthesis (1 R ,2 S )‐(+)‐ cis ‐methyldihydrojasmonate yield enantiopurity.

Язык: Английский

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Cobalt‐Catalyzed Asymmetric Hydrogenation: Substrate Specificity and Mechanistic Variability

Angewandte Chemie International Edition, Год журнала: 2023, Номер 63(10)

Опубликована: Ноя. 28, 2023

Asymmetric hydrogenation finds widespread application in academia and industry. And indeed, a number of processes have been implemented for the production pharma agro intermediates as well flavors & fragrances. Although these are all based on use late transition metals catalysts, there is an increasing interest base metal catalysis view their lower cost expected different substrate scope. Catalysts cobalt already shown potential enantioselective chemistry. This review outlines impressive progress made recent years cobalt-catalyzed asymmetric unsaturated substrates. We also illustrate ligand dependent specificity mechanistic variability detail. may guide further catalyst development this research area.

Язык: Английский

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Asymmetric Synthesis and Applications of Chiral Organoselenium Compounds: A Review

Molecules, Год журнала: 2024, Номер 29(15), С. 3685 - 3685

Опубликована: Авг. 3, 2024

The synthesis and application of organoselenium compounds have developed rapidly, chiral become an important intermediate in the field medicine, materials, organic synthesis. strategy developing a green economy is still challenge with enantioselective properties. This review covers detail from 1979 to 2024 their fields asymmetric catalysis.

Язык: Английский

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Asymmetric and Chemoselective Iridium Catalyzed Hydrogenation of Conjugated Unsaturated Oxime Ethers

Chemistry - A European Journal, Год журнала: 2024, Номер 30(39)

Опубликована: Май 23, 2024

Abstract Research on the chemoselective metal‐catalyzed hydrogenation of conjugated π‐systems has mostly been focussed enones. Herein, we communicate understudied asymmetric enimines catalyzed by N,P‐iridium complexes and toward alkene. A number enoxime ethers underwent smoothly to yield desired products in high stereopurity (up 99 % yield, up ee ). No C=N π‐bond was observed under applied reaction conditions (20 bar H 2 , rt, DCM). It demonstrated that chiral oxime ether could be hydrolyzed into ketone with complete preservation installed stereogenity at α‐carbon. At last, a binding mode substrate active iridium catalyst consequence for stereoselective outcome proposed.

Язык: Английский

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Data-Driven Insights into the Transition-Metal-Catalyzed Asymmetric Hydrogenation of Olefins

The Journal of Organic Chemistry, Год журнала: 2024, Номер 89(17), С. 12467 - 12478

Опубликована: Авг. 16, 2024

The transition-metal-catalyzed asymmetric hydrogenation of olefins is one the key transformations with great utility in various industrial applications. field has been dominated by use noble metal catalysts, such as iridium and rhodium. reactions earth-abundant cobalt have increased only recent years. In this work, we analyze large amount literature data available on iridium- rhodium-catalyzed hydrogenation. limited using Co catalysts are then examined context Ir Rh to obtain a better understanding reactivity pattern. A detailed data-driven study types olefins, ligands, reaction conditions solvent, temperature, pressure carried out. Our analysis provides an trends demonstrates that few olefin–ligand combinations or frequently used. knowledge bias toward certain group substrates can be useful for practitioners design new sets suitable meaningful predictions from machine-learning models.

Язык: Английский

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Synthetic Study towards Providencin: Stereocontrolled Synthesis of the Furan-Substituted Cyclobutanol Segment

Chemical and Pharmaceutical Bulletin, Год журнала: 2024, Номер 72(11), С. 966 - 969

Опубликована: Ноя. 14, 2024

This study explores the synthesis of unique furanocembranoid-type marine diterpenoid, providencin. Providencin features a highly oxidized structure with two furan rings, oxirane and bicyclo[12.2.0]hexadecane framework. Its potential as lead compound for drug development has drawn attention to its total synthesis, particularly focusing on challenging right-half segment involving substituted cyclobutane ring. We developed novel synthetic strategy fragment using [2 + 2] cycloaddition reaction lithium ynolates α,β-unsaturated lactone, successfully constructing bicyclic cyclobutene structure. Stereoselective hydrogenation cyclobutenes was achieved by Crabtree's catalyst under high pressure H2 atmosphere. After further transformation, furan-substituted cyclobutanol having formyl side chain accomplished.

Язык: Английский

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Recent Advances in the Asymmetric Catalytic Synthesis of Phosphonates with an α-Chiral Center

Synthesis, Год журнала: 2023, Номер 55(19), С. 3057 - 3072

Опубликована: Март 31, 2023

Abstract Phosphonates and derivatives with an α-chiral center are of great importance they widely distributed in many natural products, pharmaceuticals, agrochemicals various bioactive features. Great effort has been made toward the development efficient methods for their synthesis. In this short review, recent advances asymmetric catalytic synthesis phosphonates summarized, including hydrogenation α,β-unsaturated phosphonates, addition to unsaturated electrophiles, nucleophiles phosphonates. addition, continuous enantioselective synthetic application future prospects. 1 Introduction 2 Asymmetric Hydrogenation α,β-Unsaturated 3 Addition Unsaturated Electrophiles 4 Nucleophiles 5 Conclusion

Язык: Английский

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Access to Enantiomerically Pure P-Chiral 1-Phosphanorbornane Silyl Ethers

Molecules, Год журнала: 2023, Номер 28(17), С. 6210 - 6210

Опубликована: Авг. 23, 2023

Sulfur-protected enantiopure P-chiral 1-phosphanorbornane silyl ethers 5a,b are obtained in high yields via the reaction of hydroxy group alcohol 4 with tert-butyldimethylsilyl chloride (TBDMSCl) and triphenylsilyl (TPSCl). The corresponding optically pure purified crystallization fully structurally characterized. Desulfurization excess Raney nickel gives access to bulky monodentate phosphorus(III) 6a,b which subsequently applied as ligands iridium-catalyzed asymmetric hydrogenation a prochiral ketone enamide. Better activity selectivity were observed latter case.

Язык: Английский

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