Enantioselective Allenation of Terminal Alkynes Catalyzed by Copper Halides of Mixed Oxidation States and Its Application to the Total Synthesis of Scorodonin DOI
Guolin Wu, Yuan Yao, Gen Li

et al.

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(4)

Published: Nov. 4, 2021

Abstract Naturally occurring conjugated allenynes are of general interest owing to their potent and various biological activities. The 1,5‐H transfer alka‐1,4‐diyn‐3‐yl amines would be one the most straightforward yet challenging approaches such compounds since, in principle, two regioisomers may formed involving C−C triple bonds. Herein, a catalytic recipe copper halides with mixed oxidation states, i.e., CuCl/CuBr 2 , has been identified address issues side reaction conjugate addition selectivity EATA (enantioselective allenation terminal alkynes) 2‐alkynals. This method provided excellent enantioselectivities, was also applied first highly enantioselective total synthesis natural product scorodonin. Mechanistic studies DFT calculations elucidated regioselectivity for observed transfer.

Language: Английский

Formaldehyde-Mediated Hydride Liberation of Alkylamines for Intermolecular Reactions in Hexafluoroisopropanol DOI

Shaokun Cai,

Hong Tang,

Bo Li

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(9), P. 5952 - 5963

Published: Feb. 26, 2024

The ability of alkylamines to spontaneously liberate hydride ions is typically restrained, except under specific intramolecular reaction settings. Herein, we demonstrate that this reactivity can be unlocked through simple treatment with formaldehyde in hexafluoroisopropanol (HFIP) solvent, thereby enabling various intermolecular transfer reactions mild conditions. Besides transformations small molecules, these enable unique late-stage modification complex peptides. Mechanistic investigations uncover the key processes lies accommodating conformation solvent-mediated macrocyclic transition states, where aggregates HFIP molecules act as dexterous proton shuttles. Importantly, negative hyperconjugation between lone electron pair nitrogen and antibonding orbital amine's α C-H bond plays a critical role activation, promoting its liberation.

Language: Английский

Citations

17
Electrochemical Desaturative β‐Acylation of Cyclic N‐Aryl Amines DOI
Tian Feng, Siyi Wang, Yin Liu

et al.

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(6)

Published: Dec. 8, 2021

Abstract Herein, we disclose a straightforward, robust, and simple route to access β‐substituted desaturated cyclic amines via an electrochemically driven desaturative β‐functionalization of amines. This transformation is based on multiple single‐electron oxidation processes using catalytic amounts ferrocene. The reaction proceeds in the absence stoichiometric electrolyte under mild conditions, affording desired products with high chemo‐ regioselectivity. was tolerant broad range substrates also enables late‐stage β‐C(sp 3 )−H acylation potentially valuable products. Preliminary mechanistic studies voltammetry reveal key role ferrocene as redox mediator reaction.

Language: Английский

Citations

81
Mechanistic Investigation, Wavelength-Dependent Reactivity, and Expanded Reactivity of N–Aryl Azacycle Photomediated Ring Contractions DOI
Sojung F. Kim, Henrik Schwarz, Justin Jurczyk

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(8), P. 5580 - 5596

Published: Feb. 12, 2024

Under mild blue-light irradiation, α-acylated saturated heterocycles undergo a photomediated one-atom ring contraction that extrudes heteroatom from the cyclic core. However, for nitrogenous heterocycles, this powerful skeletal edit has been limited to substrates bearing electron-withdrawing substituents on nitrogen. Moreover, mechanism and wavelength-dependent efficiency of transformation have remained unclear. In work, we increased electron richness nitrogen in azacycles improve light absorption strengthen critical intramolecular hydrogen bonding while enabling direct installation photoreactive handle. As result, broadly expanded substrate scope, including underexplored electron-rich previously unsuccessful now achieved. The significantly improved yields diastereoselectivities facilitated reaction rate, kinetic isotope effect (KIE), quenching studies, addition determination quantum yields. Guided by these propose revised ET/PT contraction, which is additionally corroborated computational characterization lowest-energy excited states through time-dependent DFT. at wavelengths longer than those strongly absorbed was investigated rate measurements, revealed red shift photochemical action plot relative absorbance. elucidated mechanistic photophysical details effectively rationalize empirical observations, additive effects, were poorly understood. Our findings not only demonstrate enhanced synthetic utility shed but may also offer valuable guidance understanding reactivity related systems.

Language: Английский

Citations

11
Electrochemical synthesis of peptide aldehydes via C‒N bond cleavage of cyclic amines DOI Creative Commons

Xinyue Fang,

Yong Zeng,

Yawen Huang

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 18, 2024

Abstract Peptide aldehydes are crucial biomolecules essential to various biological systems, driving a continuous demand for efficient synthesis methods. Herein, we develop metal-free, facile, and biocompatible strategy direct electrochemical of unnatural peptide aldehydes. This electro-oxidative approach enabled step- atom-economical ring-opening via C‒N bond cleavage, allowing homoproline-specific diversification expansion substrate scope include amides, esters, cyclic amines sizes. The remarkable efficacy the electro-synthetic protocol set stage modification assembly linear macrocyclic peptides using concise synthetic sequence with racemization-free conditions. Moreover, combination experiments density functional theory (DFT) calculations indicates that different N -acyl groups play decisive role in reaction activity.

Language: Английский

Citations

11
Dual Relay Rh-/Pd-Catalysis Enables β-C(sp3)-H Arylation of α-Substituted Amines DOI Creative Commons
Shuailong Li, Sani Yahaya, Jan Bojanowski

et al.

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

Published: Jan. 1, 2025

A dual relay catalytic protocol, built on reversible dehydrogenation of amines by Rh catalysis and C-H functionalisation transient imines Pd catalysis, is reported to enable regioselective arylation at their unactivated β-C(sp3)-H bond. Notably, the new strategy applicable secondary anilines N-PMP-protected primary aliphatic intermediate steric demands, which in contrast existing strategies that involve either free-amine-directed activation for highly sterically hindered or steric-controlled migrative cross-coupling unhindered N-Boc protected amines. Regioselectivity reaction imposed electronic effects imine intermediates rather than between specific starting materials catalysts, thereby opening uncharted scope In a broader sense, this study demonstrates opportunities involving hydrogen borrowing chemistry, previously explored alcohols, execute otherwise challenging transformations amines, commonly present natural products, pharmaceuticals, biologically active molecules, functional materials.

Language: Английский

Citations

1
Nickel‐Catalyzed Site‐Selective Intermolecular C(sp3)−H Amidation DOI
Jinhong Chen, Hao Wang, Craig S. Day

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(50)

Published: Oct. 18, 2022

A nickel-catalyzed site-selective intermolecular amidation of saturated C(sp3 )-H bonds is reported. This mild protocol exhibits a predictable reactivity pattern to incorporate amide functions at sites adjacent nitrogen and oxygen atoms in either cyclic or acyclic frameworks, thus offering complementary profile existing oxidative-type processes metal-catalyzed )-N bond-forming reactions operating via two-electron manifolds.

Language: Английский

Citations

27
N-Dealkylation of Amines DOI Creative Commons
Ali Alipour Najmi, Rainer Bischoff, Hjalmar P. Permentier

et al.

Molecules, Journal Year: 2022, Volume and Issue: 27(10), P. 3293 - 3293

Published: May 20, 2022

N-dealkylation, the removal of an N-alkyl group from amine, is important chemical transformation which provides routes for synthesis a wide range pharmaceuticals, agrochemicals, bulk and fine chemicals. N-dealkylation amines also in vivo metabolic pathway metabolism xenobiotics. Identification drug metabolites such as N-dealkylated are necessary throughout all phases development studies. In this review, different approaches including chemical, catalytic, electrochemical, photochemical enzymatic methods will be discussed.

Language: Английский

Citations

25
Photocatalytic Decarboxylative Alkylation of Cyclic Imine–BF3 Complexes: A Modular Route to Functionalized Azacycles DOI
Kamal Bhatt,

Alafate Adili,

Andrew Tran

et al.

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

Published: Sept. 12, 2024

Alkyl radicals generated via an acridine photocatalyzed decarboxylation reaction of feedstock carboxylic acids engage with a range cyclic imine-BF

Language: Английский

Citations

5
Photoinduced α‐C−H Amination of Cyclic Amine Scaffolds Enabled by Polar‐Radical Relay DOI
Wongyu Lee, Dongwook Kim, Sangwon Seo

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(25)

Published: April 11, 2022

Herein, we report a polar-radical relay strategy for α-C-H amination of cyclic amines with N-chloro-N-sodio-carbamates. The is initiated by in situ generation iminium intermediate using N-iodosuccinimide (NIS) oxidant as an initiator, which then operates through series polar (addition and elimination) radical (homolysis, hydrogen- halogen atom transfer) reactions to enable the challenging C-N bond formation controlled manner. A broad range α-amino were readily accessed excellent regioselectivity, superb applicability was further demonstrated functionalization biologically relevant compounds.

Language: Английский

Citations

22
Transition-Metal-Catalyzed Remote C–H Bond Functionalization of Cyclic Amines DOI Creative Commons
Weijie Chen, Xiaoyu Yang, Xi Cao

et al.

SynOpen, Journal Year: 2022, Volume and Issue: 06(04), P. 286 - 305

Published: Aug. 24, 2022

Abstract C–H bond functionalization is one of the most effective strategies for rapid synthesis cyclic amines containing substituents on ring, which are core structures many bioactive molecules. However, it much more challenging to perform this strategy remote bonds compared α-C–H amines. This graphical review aims provide a concise overview transition-metal-catalyzed methods Examples categorized and demonstrated according mechanistic pathways that initiate reactions amine substrates. Where relevant, selected substrate scope detailed reaction mechanisms given.

Language: Английский

Citations

19