Remote Steric and Electronic Effects of N-Heterocyclic Carbene Ligands on Alkene Reactivity and Regioselectivity toward Hydrocupration Reactions: The Role of Expanded-Ring N-Heterocyclic Carbenes DOI
Aqeel A. Hussein, Azhar Ariffin

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(18), P. 13009 - 13021

Published: Aug. 31, 2023

The remote groups in N-heterocyclic carbene (NHC) ligands have a significant influence on metal-catalyzed reactions. We examine how bulkiness, electronic groups, and expanded-ring NHCs (ER-NHCs) alkene reactivity regioselectivity toward hydrocupration using density functional theory calculations. impact of steric bulkiness the Cu–H insertion rate is analyzed, revealing strong correlation between substituent constant ratio, where bulky group increases due to reduced effects transition state (TS). properties examined catalysts (with R2 = CPh3, CHPh2, CH2Ph, CH3, H) their corresponding TSs are found be modulated greatly by substitution ring size NHC ligand. Enhanced enhances nucleophilic moiety. smaller barrier compared that hindrance. Furthermore, ER-NHC exploration indicates with over five-membered rings significantly negative reaction rate. Finally, highly (R2 CPh3), anti-Markovnikov preference attributed high interaction energy improved properties. Overall, our findings here provide valuable insights for development more effective catalyst

Language: Английский

Anti-Markovnikov Intermolecular Hydroamination of Alkenes and Alkynes: A Mechanistic View DOI Creative Commons
Jorge Escorihuela, Agustı́ Lledós, Gregori Ujaque

et al.

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(15), P. 9139 - 9203

Published: July 5, 2023

Hydroamination, the addition of an N–H bond across a C–C multiple bond, is reaction with great synthetic potential. Important advances have been made in last decades concerning catalysis these reactions. However, controlling regioselectivity amine toward formation anti-Markovnikov products (addition to less substituted carbon) still remains challenge, particularly intermolecular hydroaminations alkenes and alkynes. The goal this review collect systems which hydroamination terminal alkynes has achieved. focus will be placed on mechanistic aspects such reactions, discern step at decided unravel factors that favor regioselectivity. In processes entailing direct alternative pathways, involving several reactions accomplish (formal processes), also discussed review. catalysts gathered embrace most metal groups Periodic Table. Finally, section discussing radical-mediated metal-free approaches, as well heterogeneous catalyzed processes, included.

Language: Английский

Citations

58
Regioselective and Enantioselective Copper‐Catalyzed Hydroaminocarbonylation of Unactivated Alkenes and Alkynes DOI Creative Commons
Yang Yuan, Youcan Zhang, Wenbo Li

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(40)

Published: Aug. 16, 2023

Given the prevalence of amide backbones in marketed pharmaceuticals and their ubiquity as critical binding units natural peptides proteins, it remains important to develop novel methods construct bonds. We report here a general method for anti-Markovnikov hydroaminocarbonylation unactivated alkenes under mild conditions, using copper catalysis combination with hydroxylamine electrophile reagents poly(methylhydrosiloxane) (PMHS) cheap environmentally friendly hydride source. The reaction tolerates variety functional groups efficiently converts terminal alkenes, 1,1-disubstituted cyclic corresponding amides exclusive selectivity (and high enantioselectivities/diastereoselectivities). Additionally, minimal modification alkynes can also undergo tandem hydrogenation-hydroaminocarbonylation alkyl amides.

Language: Английский

Citations

23
Copper‐Catalyzed Dearomative 1,2‐Hydroamination DOI Creative Commons
Christopher William Davis, Yu Zhang, Yanrong Li

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(32)

Published: May 23, 2024

Catalytic olefin hydroamination reactions are some of the most atom-economical transformations that bridge readily available starting materials-olefins and high-value-added amines. Despite significant advances in this field over last two decades, formal nonactivated aromatic compounds remains an unsolved challenge. Herein, we report extension to π-systems by using arenophile-mediated dearomatization Cu-catalysis perform 1,2-hydroamination on arenes. This strategy was applied a variety substituted arenes heteroarenes provide general access structurally complex We conducted DFT calculations inform mechanistic understanding rationalize unexpected selectivity trends. Furthermore, developed practical, scalable desymmetrization deliver enantioenriched dearomatized products enable downstream synthetic applications. ultimately used dearomative efficiently synthesize collection densely functionalized small molecules.

Language: Английский

Citations

6
Copper-Catalyzed Carbonylation Reactions: A Personal Account DOI
Xiao‐Feng Wu, Hui‐Qing Geng

Synthesis, Journal Year: 2024, Volume and Issue: 56(17), P. 2595 - 2613

Published: Jan. 9, 2024

Abstract Carbonylation reactions have been widely used to construct carbonyl-containing molecules or carbon enhancement reactions, which are mostly catalyzed by noble metals (Pd, Rh, Ru, Ir). In this review, we introduce the copper-catalyzed carbonylation that developed in our group. Diverse using various substrates, including of C–H activated alkanes, difunctionalization unsaturated C–C bonds, and alkyl halides via radical pathway. 1 Introduction 2 Cu-Catalyzed C(sp 3)–H Bonds 3 Carbonylative Difunctionalization Unsaturated 4 Cu–X (H B) Mediated Acylation with Electrophiles 5 6 Alkyl Halides 7 Other Types Copper-Catalyzed Reactions 8 Conclusion Outlook

Language: Английский

Citations

5
Lewis Acid-Catalyzed Carbonyl-Ene Reaction: Interplay between Aromaticity, Synchronicity, and Pauli Repulsion DOI Creative Commons
Humberto A. Rodríguez, Daniel A. Cruz, Juan I. Padrón

et al.

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(15), P. 11102 - 11110

Published: July 24, 2023

The physical factors governing the catalysis in Lewis acid-promoted carbonyl-ene reactions have been explored detail quantum chemically. It is found that binding of a acid to carbonyl group directly involved transformation greatly accelerates reaction by decreasing corresponding activation barrier up 25 kcal/mol. makes process much more asynchronous and transition state less in-plane aromatic. remarkable acceleration induced catalyst ascribed, means strain model energy decomposition analysis methods, mainly significant reduction Pauli repulsion between key occupied π-molecular orbitals reactants not widely accepted stabilization LUMO enophile.

Language: Английский

Citations

12
Computational Tools for the Prediction of Site- and Regioselectivity of Organic Reactions DOI Creative Commons
Lukas M. Sigmund,

Michele Assante,

Magnus J. Johansson

et al.

Chemical Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

This article reviews computational tools for the prediction of regio- and site-selectivity organic reactions. It spans from quantum chemical procedures to deep learning models showcases application presented tools.

Language: Английский

Citations

0
Origin of site-selectivity of hydrogen atom transfer in carbohydrate C–H alkylations via photoredox catalysis DOI
Yujie Ji,

Lingfei Hu,

Han Gao

et al.

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(8), P. 2269 - 2276

Published: Jan. 1, 2024

Two major factors, i.e. , C–H σ orbital energy and BDE, account for the HAT site-selectivity of carbohydrates with quinuclidine radical cation.

Language: Английский

Citations

1
Regioselective and Enantioselective Copper‐Catalyzed Hydroaminocarbonylation of Unactivated Alkenes and Alkynes DOI Creative Commons
Yang Yuan, Youcan Zhang, Wenbo Li

et al.

Angewandte Chemie, Journal Year: 2023, Volume and Issue: 135(40)

Published: Aug. 16, 2023

Abstract Given the prevalence of amide backbones in marketed pharmaceuticals and their ubiquity as critical binding units natural peptides proteins, it remains important to develop novel methods construct bonds. We report here a general method for anti‐Markovnikov hydroaminocarbonylation unactivated alkenes under mild conditions, using copper catalysis combination with hydroxylamine electrophile reagents poly(methylhydrosiloxane) (PMHS) cheap environmentally friendly hydride source. The reaction tolerates variety functional groups efficiently converts terminal alkenes, 1,1‐disubstituted cyclic corresponding amides exclusive selectivity (and high enantioselectivities/diastereoselectivities). Additionally, minimal modification alkynes can also undergo tandem hydrogenation‐hydroaminocarbonylation alkyl amides.

Language: Английский

Citations

2
Mechanistic Insights into the DABCO-Catalyzed Cloke–Wilson Rearrangement: A DFT Perspective DOI Creative Commons
Sebastián Gallardo‐Fuentes, Lucas Lodeiro, Ricardo A. Matute

et al.

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(22), P. 15902 - 15912

Published: Oct. 27, 2023

The mechanism and selectivity patterns of the DABCO-catalyzed Cloke-Wilson rearrangement were computationally studied in detail using density functional theory calculations. Our computations suggest that process occurs stepwise involving initial ring opening cyclopropane promoted by a DABCO molecule followed ring-closure reaction readily formed zwitterionic intermediate. regioselectivity nucleophilic ring-opening step strongly depends on nature substituent attached to moiety. physical factors governing preference for more sterically hindered C2 (tertiary) position have been quantitatively analyzed applying combined activation strain model-energy decomposition analysis method. In addition, our calculations revealed new analogous transformation vinylcyclopropanes consisting an SN2' 5-exo-trig cyclization step, which proceeds without facial selectivity.

Language: Английский

Citations

2
Copper‐Catalyzed Dearomative 1,2‐Hydroamination DOI Creative Commons
Christopher William Davis, Yu Zhang, Yanrong Li

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(32)

Published: May 23, 2024

Abstract Catalytic olefin hydroamination reactions are some of the most atom‐economical transformations that bridge readily available starting materials–olefins and high‐value‐added amines. Despite significant advances in this field over last two decades, formal nonactivated aromatic compounds remains an unsolved challenge. Herein, we report extension to π‐systems by using arenophile‐mediated dearomatization Cu‐catalysis perform 1,2‐hydroamination on arenes. This strategy was applied a variety substituted arenes heteroarenes provide general access structurally complex We conducted DFT calculations inform mechanistic understanding rationalize unexpected selectivity trends. Furthermore, developed practical, scalable desymmetrization deliver enantioenriched dearomatized products enable downstream synthetic applications. ultimately used dearomative efficiently synthesize collection densely functionalized small molecules.

Language: Английский

Citations

0