Practical synthesis of allylic amines via nickel-catalysed multicomponent coupling of alkenes, aldehydes, and amides

Chemical Science, Год журнала: 2023, Номер 14(32), С. 8644 - 8650

Опубликована: Янв. 1, 2023

Molecules with an allylic amine motif provide access to important building blocks and versatile applications of biologically relevant chemical space. The need for diverse amines requires the development increasingly general modular multicomponent reactions synthesis. Herein, we report efficient catalytic coupling reaction simple alkenes, aldehydes, amides by combining nickel catalysis Lewis acid catalysis, thus providing a practical, environmentally friendly, protocol build architecturally complex functionally in single step. method is remarkably simple, shows broad functional-group tolerance, facilitates synthesis drug-like that are not readily accessible other methods. utilization starting materials inexpensive Ni(ii) salt as alternative precatalyst offers significant practical advantage. In addition, practicality process was also demonstrated efficient, gram-scale preparation prostaglandin agonist.

Язык: Английский

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Enantioselective and Diastereodivergent Allylation of Propargylic C–H Bonds

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(34), С. 15480 - 15487

Опубликована: Авг. 17, 2022

An iridium-catalyzed stereoselective coupling of allylic ethers and alkynes to generate 3,4-substituted 1,5-enynes is reported. Under optimized conditions, the products are formed with excellent regio-, diastereo-, enantioselectivities, protocol functional group tolerant. Moreover, we report conditions that allow reaction proceed complete reversal diastereoselectivity. Mechanistic studies consistent an unprecedented dual role for iridium catalyst, enabling propargylic deprotonation alkyne through π-coordination, as well generation a π-allyl species from ether starting material.

Язык: Английский

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Asymmetric α-C(sp3)−H allylic alkylation of primary alkylamines by synergistic Ir/ketone catalysis

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 31, 2024

Abstract Primary alkyl amines are highly reactive in N-nucleophilic reactions with electrophiles. However, their α-C−H bonds unreactive towards electrophiles due to extremely low acidity (p K a ~57). Nonetheless, 1,8-diazafluoren-9-one (DFO) can activate primary by increasing the of α-amino C−H up 10 44 times. This makes acidic enough be deprotonated under mild conditions. By combining DFO an iridium catalyst, direct asymmetric alkylation NH 2 -unprotected allylic carbonates has been achieved. reaction produces wide range chiral homoallylic high enantiopurities. The approach successfully switched reactivity between and from intrinsic amination alkylation, enabling construction pharmaceutically significant readily available single step.

Язык: Английский

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COAP‐Palladium‐Catalyzed Asymmetric Linear Allylic Alkylation of Vinyl Benzoxazinanones for Multifunctional 3,3′‐Disubstituted Oxindole Derivatives

Advanced Synthesis & Catalysis, Год журнала: 2023, Номер 365(8), С. 1268 - 1274

Опубликована: Март 16, 2023

Abstract A Pd‐catalyzed enantioselective linear‐allylic alkylation of vinyl benzoxazinanones with a series 3‐substituted oxindoles was reported in the presence chiral oxamide‐phosphine ligand (COAP−Bn) under mild reaction conditions. optically active multifunctional 3,3′‐disubstituted oxindole derivatives bearing quaternary stereogenic center and linear aryl amino side chain were respectively obtained 55–98% yields 96–99% ee for 3‐(hetero)aryl substituted oxindoles. The developed protocol demonstrates that COAP ligands could serve as privileged to construct diverse 3,3‐disubstituted compounds various centers, such aza ‐, thio ‐ or all‐carbon centers. salient features method include broad substrate scope, N ‐protecting group free, base‐free, high regio‐ enantioselectivity. magnified image

Язык: Английский

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Machine Learning for Reaction Performance Prediction in Allylic Substitution Enhanced by Automatic Extraction of a Substrate-Aware Descriptor

Journal of Chemical Information and Modeling, Год журнала: 2025, Номер 65(1), С. 312 - 325

Опубликована: Янв. 2, 2025

Despite remarkable advancements in the organic synthesis field facilitated by use of machine learning (ML) techniques, prediction reaction outcomes, including yield estimation, catalyst optimization, and mechanism identification, continues to pose a significant challenge. This challenge arises primarily from lack appropriate descriptors capable retaining crucial molecular information for accurate while also ensuring computational efficiency. study presents successful application ML predicting performance Ir-catalyzed allylic substitution reactions. We introduce SubA, an innovative substrate-aware descriptor that is inspired fact specific atoms or motifs reactants drive outcomes. By employing graph matching algorithms backbone identification incorporating atomic properties derived density functional theory calculations, SubA extracts essential at both level level. Compared four mainstream descriptors, achieves reduced dimensionality enhanced accuracy with over 2% mean absolute error reduction random scaffold splitting evaluations. It demonstrates better generalization when confronted previously unreported substrate combinations extended experiments. Furthermore, interpretable analysis shows predictor focuses on key features, offering insights into mechanisms.

Язык: Английский

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Synthesis of vinyl, alkyl-substituted chiral acrylates via Krische iridium complex-catalysed allylic phosphonation

Chemical Communications, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

An enantioselective preparation of vinyl, alkyl-substituted chiral α-stereogenic acrylates is reported using two consecutive steps Ir-catalysed allylic alkylation aliphatic acetates with phosphonates and HWE olefination.

Язык: Английский

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Visible light-mediated decarboxylative allylic alkylation of Morita–Baylis–Hillman acetates with unactivated aliphatic acids

Organic & Biomolecular Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Herein, a visible light-induced and metal-free strategy for the direct decarboxylative allylic alkylation of Morita–Baylis–Hillman acetates with aliphatic acids under redox-neutral conditions has been developed.

Язык: Английский

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Enantiospecific Synthesis of α-Tertiary Amines: Ruthenium-Catalyzed Allylic Amination with Aqueous Ammonia

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

Опубликована: Март 27, 2025

Ammonia stands out as the most available, cost-effective, and atom-economical source of nitrogen for organic synthesis. In laboratory, it is safely conveniently handled in aqueous solution. Despite advantages, direct application ammonia field transition-metal catalysis remains a significant challenge. this study, we report first ruthenium-catalyzed allylic substitution using ammonia. The catalytic system, consisting [Cp*Ru(MeCN)3]PF6 phenoxythiazoline ligand, enables enantiospecific amination tertiary carbonates media affords enantioenriched primary amines single regioisomers high yields.

Язык: Английский

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Asymmetric Synthesis of Tetrahydrofurans with Vicinal Stereocenters by Rh^II/Ru^II Relay Catalysis

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

Опубликована: Апрель 25, 2025

CpRu-catalyzed asymmetric allylic alkylation serves as a versatile synthetic tool but remains underexplored. Herein, we report relay system combining achiral Rh2(OAc)4 and chiral pyridine-oxazoline-ligated Cp*Ru catalyst for coupling of cinnamyl chlorides with diazo esters, generating silyl enol ethers in situ key nucleophilic intermediates. This strategy affords tetrahydrofuran derivatives two vicinal stereocenters. Catalyst compatibility, excellent regioselectivity, good enantioselectivity highlight its potential. Computational studies reveal the crucial role Ru-centered chirality reaction control.

Язык: Английский

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Asymmetric Bimetallic Catalysis Enabled Alkenyl Z/E Mutual Isomerization

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

Опубликована: Июнь 5, 2025

Olefins are fundamental functional groups present in numerous molecules, and the geometrical configuration of C═C bonds often plays a critical role determining properties these compounds. Alkenyl isomerization is, principle, one most efficient approaches for accessing stereodefined olefins. While some progress has been made achieving unidirectional Z → E or conversion via olefin isomerization, there remains strong demand controllable, bidirectional bonds. Herein, we method Z/E mutual alkenyl by using Pd/Cu catalytic system. This process involves Pd-mediated π-σ-π interconversion followed selective trapping π-allyl-Pd intermediates with N-metalated azomethine ylides generated chiral Cu-catalyst. The reaction enables synthesis non-natural amino acid derivatives bearing Z- E-alkenyl an enantio- Z/E-divergent manner, yields up to 92%, > 20:1 E/Z, >99% ee. Furthermore, is scalable gram quantities, resulting products can be transformed into valuable molecules adorned groups. Computational studies show that bimetallic system better distinguishes among eight stereoisomers than monometallic system, which results exceptional Z/E-selectivity products. offers robust protocol synthesizing E-trisubstituted olefins motif utilizing readily available Z/E-mixture substrates.

Язык: Английский

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