![Mizoroki-Heck Cross-coupling Reactions Catalyzed by Dichloro{bis[1,1',1''-phosphinetriyltripiperidine]}palladium Under Mild Reaction Conditions](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F51444.jpg&w=3840&q=50)
Electrocatalytic C(sp3)-H/C(sp)-H cross-coupling in continuous flow through TEMPO/copper relay catalysis.
1Key Laboratory of Chemical Biology of Fujian Province and College of Chemistry and Chemical Engineering, Xiamen University, People's Republic of China.
Beilstein Journal of Organic Chemistry
|November 19, 2021
Summary
This study presents a new electrocatalytic method for coupling tetrahydroisoquinolines and alkynes. This sustainable process, utilizing TEMPO/copper catalysis in flow, offers efficient access to valuable 2-functionalized tetrahydroisoquinolines.
Area of Science:
- Organic Chemistry
- Catalysis
- Flow Chemistry
Background:
- Tetrahydroisoquinolines are important scaffolds in medicinal chemistry.
- Efficient synthesis of functionalized tetrahydroisoquinolines is crucial.
- C-H activation/coupling reactions offer atom-economical synthetic routes.
Purpose of the Study:
- To develop a novel electrocatalytic method for C(sp³)-H/C(sp)-H cross-coupling.
- To synthesize 2-functionalized tetrahydroisoquinolines using terminal alkynes.
- To implement the reaction in a continuous-flow microreactor system.
Main Methods:
- Electrocatalytic dehydrogenative cross-coupling reaction.
- Utilizing 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) and copper relay catalysis.
- Performing the reaction in a continuous-flow microreactor.
Main Results:
- Successful C(sp³)-H/C(sp)-H cross-coupling of tetrahydroisoquinolines with terminal alkynes.
- The reaction is scalable and operates under mild conditions.
- Low supporting electrolyte concentration and no external oxidants or ligands were required.
Conclusions:
- The developed method provides a straightforward and sustainable route to 2-functionalized tetrahydroisoquinolines.
- Continuous-flow microreactor technology enhances reaction efficiency and scalability.
- This approach offers a greener alternative for synthesizing valuable heterocyclic compounds.
![[DPEPhosbcpCu]PF6: A General and Broadly Applicable Copper-Based Photoredox Catalyst](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F59739.jpg&w=3840&q=50)
Related Concept Videos
01:26Thermal and Photochemical Electrocyclic Reactions: Overview
2.5K
Electrocyclic reactions are reversible reactions. They involve an intramolecular cyclization or ring-opening of a conjugated polyene. Shown below are two examples of electrocyclic reactions. In the first reaction, the formation of the cyclic product is favored. In contrast, in the second reaction, ring-opening is favored due to the high ring strain associated with cyclobutene formation.
2.5K
01:17Thermal Electrocyclic Reactions: Stereochemistry
2.1K
The stereochemistry of electrocyclic reactions is strongly influenced by the orbital symmetry of the polyene HOMO. Under thermal conditions, the reaction proceeds via the ground-state HOMO.
Selection Rules: Thermal Activation
Conjugated systems containing an even number of π-electron pairs undergo a conrotatory ring closure. For example, thermal electrocyclization of (2E,4E)-2,4-hexadiene, a conjugated diene containing two π-electron pairs, gives trans-3,4-dimethylcyclobutene.
Selection Rules: Thermal Activation
Conjugated systems containing an even number of π-electron pairs undergo a conrotatory ring closure. For example, thermal electrocyclization of (2E,4E)-2,4-hexadiene, a conjugated diene containing two π-electron pairs, gives trans-3,4-dimethylcyclobutene.
2.1K
01:28Reduction of Benzene to Cyclohexane: Catalytic Hydrogenation
5.1K
Unlike the easy catalytic hydrogenation of an alkene double bond, hydrogenation of a benzene double bond under similar reaction conditions does not take place easily. For example, in the reduction of stilbene, the benzene ring remains unaffected while the alkene bond gets reduced. Hydrogenation of an alkene double bond is exothermic and a favorable process. In contrast, to hydrogenate the first unsaturated bond of benzene, an energy input is needed; that is, the process is endothermic. This is...
5.1K
01:17Pericyclic Reactions: Introduction
8.6K
Pericyclic reactions are organic reactions that occur via a concerted mechanism without generating any intermediates. The reactions proceed through the movement of electrons in a closed loop to form a cyclic transition state, where rearrangement of the σ and π bonds yields specific products.
Pericyclic reactions can be classified into three categories: electrocyclic reactions, cycloaddition reactions, and sigmatropic rearrangements. Electrocyclic reactions and sigmatropic...
Pericyclic reactions can be classified into three categories: electrocyclic reactions, cycloaddition reactions, and sigmatropic rearrangements. Electrocyclic reactions and sigmatropic...
8.6K
01:10Voltammetric Techniques: Cyclic Voltammetry
782
Cyclic voltammetry (CV) is an electrochemical technique used to investigate the redox properties of a chemical species. It involves measuring the current response of an electrochemical cell as a function of the applied potential. The setup for cyclic voltammetry typically consists of a working electrode, a reference electrode, and a counter electrode—all immersed in an electrolyte solution. The working electrode is where the redox reaction of interest occurs, while the reference electrode...
782
01:16Cycloaddition Reactions: Overview
2.9K
Cycloadditions are one of the most valuable and effective synthesis routes to form cyclic compounds. These are concerted pericyclic reactions between two unsaturated compounds resulting in a cyclic product with two new σ bonds formed at the expense of π bonds. The [4 + 2] cycloaddition, known as the Diels–Alder reaction, is the most common. The other example is a [2 + 2] cycloaddition.
2.9K