Selective Hydrofunctionalization of N-Allenyl Derivatives with Heteronucleophiles Catalyzed by Brønsted Acids DOI
Arianna Quintavalla, Davide Carboni, Alessandro Brusa

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(4), P. 2320 - 2342

Published: Feb. 1, 2024

In this study, we present a novel and environmentally sustainable protocol for the γ-hydrofunctionalization of N-allenyl compounds using various heteronucleophiles catalyzed solely by simple Brønsted acids. The method displays remarkable attributes, highlighting its sustainability, efficiency, regio- stereoselectivity, as well versatile applicability to diverse heteroatom-containing enamides. Notably, our approach eliminates need metal catalysts toxic solvents, representing significant advancement in greener chemistry practices. We demonstrate broad scope successfully scaling up reactions gram-scale syntheses, underscoring robustness potential industrial implementation. resulting γ-heterosubstituted enamides offer new possibilities further synthetic transformations, yielding highly functionalized with applications. Mechanistic investigations reveal pivotal role CSA catalyst, enabling alcohol addition via covalent activation mode.

Language: Английский

Intermediate Control: Unlocking Hitherto Unknown Reactivity and Selectivity in N-Conjugated Allenes and Alkynes DOI
Tapas R. Pradhan, Jin Kyoon Park

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: 58(2), P. 281 - 298

Published: Jan. 3, 2025

ConspectusControlling selectivity through manipulation of reaction intermediates remains one the most enduring challenges in organic chemistry, providing novel solutions for selective C-C π-bond functionalization. This approach, guided by activation principles, provides an effective method functional group installation, enabling direct synthesis molecules that are inaccessible conventional pathways. In particular, functionalization N-conjugated allenes and alkynes has emerged as a promising research focus, driven advances controlling reactive strategies. this regard, our group, alongside others, established some new approaches have suitable platform functionalized enamides. Account reviews recent developments field, highlighting modes reactivity selectivity, atom-economical functionalizations, strategies regio- stereocontrol, while mechanistic insights into related transformations.Our study is systematically organized two sections based on substrate type chronological progression. first section, we establish allenamide-derived intermediates, both allenamide-alkyne (AA) cross-coupling few electrophile-promoted hydrofunctionalization reactions. The unprecedented Pd-catalyzed achieved neighboring chelation, with phosphine ligand selection outcome. parallel, functionalizations─including haloalkynylation, hydrooxycarbonylation, hydrodifluoroalkylation, intermolecular hydroamination─are strategic electrophiles or their precursors.Additionally, findings demonstrate how ynamides' toward nucleophiles, controlled activator modulation, expands scope accessible transformations. Key include: (1) chemoselective [2 + 2 2] annulation efficient trapping N-arylated nitrilium ynamides, (2) divergent C-H indole-derived vinylogous ynamides metal via intramolecular hydroarylation, (3) bromoalkynylation-enabled migration 1,3-alkynyl shift.The final section explores N-electron polarization 1,3-enynes enables chemoselectivity metal-free inter- couplings indole substrates. Our modulating conjugation within enyne skeleton─through linear cross conjugation─can pathways control product selectivity.This aims to stimulate broader intermediate-controlled activated π-systems. Future directions include advanced design, strategies, deeper studies enable rational development.

Language: Английский

Citations

1
Hydrogen-Bonding Network-Enabled Terminal Selective Heteroarylation of Allenamides in Hexafluoroisopropanol DOI
Sachin Balaso Mohite, Partha Sarathi Bera, Yafia Kousin Mirza

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

Hexafluoroisopropanol (HFIP)-mediated terminal selective heteroarylation of allenamides has been accomplished through H-bonding network-enabled substrate activation in a robust fashion. This strategy features cascade process involving sequential nucleophilic addition followed by electrophilic heteroaromatic substitution and is well suited for late-stage functionalization complex bioactive molecules. The elucidation the underlying mechanism was achieved comprehensive combination several control experiments, kinetic studies, isotopic labeling isolation HFIP-allenamide intermediate adduct.

Language: Английский

Citations

1
Hydro-phosphorothiolation of Styrene and Cyclopropane with S-Hydrogen Phosphorothioates under Ambient Conditions DOI

Biswajit Sarkar,

Alakananda Hajra

Organic Letters, Journal Year: 2024, Volume and Issue: 26(24), P. 5141 - 5145

Published: June 7, 2024

A metal-free hexafluoroisopropanol-mediated hydro-phosphorothiolation of styrenes and donor-acceptor cyclopropanes with

Language: Английский

Citations

8
Allure of HFIP in Unsaturated Carbon−Carbon Bond Functionalization DOI
Suman Ghosh, Koushik Patra, Mahiuddin Baidya

et al.

European Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 27(12)

Published: Feb. 14, 2024

Abstract Hexafluoroisopropanol (HFIP) stands out as a versatile solvent in synthetic chemists’ repertoire, facilitating diverse array of intricate chemical reactions. It demonstrates multifaceted role that extends beyond conventional uses and, many cases, the mechanism appears to be complicated. This feature article elucidates significance HFIP context Lewis and Brønsted acid‐catalyzed reactions with specific emphasis on regio‐ stereoselective functionalization unsaturated carbon‐carbon bonds.

Language: Английский

Citations

4
Acetate Assistance in Regioselective Hydroamination of Allenamides: A Combined Experimental and Density Functional Theory Study DOI
Tapas R. Pradhan, Abdikani Omar Farah,

Kadiyala Sagar

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(9), P. 5927 - 5940

Published: April 23, 2024

A key factor in the development of selective nucleophilic addition to allenamides is controlling reactivity electrophilic intermediates, which generally achieved using an activator via conjugated iminium intermediates. In this combined experimental and computational study, we show that a general highly chemoselective hydroamination can be accomplished combination 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) NaOAc. Experimental mechanistic studies revealed HFIP mediates proton transfer activate allenamide, while acetate additive significantly contributes N-selective interception. This strategy enables without use metals. We demonstrated various functionalized 1,3-diamines could readily synthesized diversified into value-added structural motifs. Detailed investigations density functional theory role NaOAc formation reactive ultimately governed 1,3-diamine products. Critically, calculations potential energy surface around proton-transfer transition state two different intermediates were formed when was added.

Language: Английский

Citations

4
HFIP-Mediated Cascade Aminomethylation and Intramolecular Cyclization of Allenamides with N,O-Acetals to Access Tetrahydro-β-carboline Derivatives DOI

Dhananjay Chaudhary,

Chandra Kant Maurya,

Urmila Unnikrishnan

et al.

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

Published: Jan. 1, 2025

A cascade of two C–C bond forming reactions promoted alone by HFIP is described delivering tetrahydro-β-carboline derivatives embedded with an allylic amine functionality.

Language: Английский

Citations

0
Regio- and Stereoselective Hexafluoroisopropoxylation and Trifluoroethoxylation of Allenamides DOI

Dhananjay Chaudhary,

Malleswara Rao Kuram

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(10), P. 7347 - 7351

Published: Jan. 2, 2024

Incorporating fluorinated moieties into organic molecules is an attractive strategy to enhance drug-like properties. Herein, we have developed a simple and self-promoted protocol for hexafluoroisopropoxylation trifluoroethoxylation of allenamides with alcohols such as HFIP TFE. The reaction provided the fluoroalkoxylated products in regio- stereoselective manner good moderate yields under mild conditions.

Language: Английский

Citations

3
Hexafluoroisopropanol (HFIP)-Mediated Intramolecular Cyclization of Allenamides To Access C1-Vinyl Tetrahydro-β-carbolines DOI

Dhananjay Chaudhary,

Malleswara Rao Kuram

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(16), P. 11783 - 11788

Published: July 26, 2024

The construction of biologically interesting N-heterocycles under metal-free conditions is a constant goal in industry and academia. Herein, we have developed an hexafluoroisopropanol (HFIP)-mediated intramolecular cyclization allenamides, providing tetrahydro-β-carboline derivatives embedded with C1-vinyl functionality. protocol provided atom-efficiently room temperature broad substrate scope good to excellent yields. potential impact the further highlighted by synthesizing important molecules diversified scaffolds via postsynthetic modifications.

Language: Английский

Citations

3
Selective Hydrofunctionalization of N-Allenyl Derivatives with Heteronucleophiles Catalyzed by Brønsted Acids DOI
Arianna Quintavalla, Davide Carboni, Alessandro Brusa

et al.

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(4), P. 2320 - 2342

Published: Feb. 1, 2024

In this study, we present a novel and environmentally sustainable protocol for the γ-hydrofunctionalization of N-allenyl compounds using various heteronucleophiles catalyzed solely by simple Brønsted acids. The method displays remarkable attributes, highlighting its sustainability, efficiency, regio- stereoselectivity, as well versatile applicability to diverse heteroatom-containing enamides. Notably, our approach eliminates need metal catalysts toxic solvents, representing significant advancement in greener chemistry practices. We demonstrate broad scope successfully scaling up reactions gram-scale syntheses, underscoring robustness potential industrial implementation. resulting γ-heterosubstituted enamides offer new possibilities further synthetic transformations, yielding highly functionalized with applications. Mechanistic investigations reveal pivotal role CSA catalyst, enabling alcohol addition via covalent activation mode.

Language: Английский

Citations

2