Copper-Catalyzed Radical Allene C(sp2 )-H Cyanation
Youhao Wei1, Zheng Wang1, Kaifeng Wang1
1Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 199 Ren-Ai Road, Suzhou, Jiangsu, 215123, China.
Angewandte Chemie (International Ed. in English)
|December 1, 2023
Summary
This study presents a new copper-catalyzed method for direct C(sp2)-H cyanation of allenes. The strategy achieves high site-selectivity, overcoming challenges in functionalizing these unique unsaturated systems.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Catalysis
Background:
- Hydrogen atom abstraction (HAA) from C(sp3)-H bonds is well-established.
- Radical-mediated functionalization of allenic C(sp2)-H bonds via direct HAA remains a significant challenge.
- Challenges include radical intermediate addition to allenes, regioselectivity, and allenyl radical stability.
Purpose of the Study:
- To develop a chemo- and regio-selective method for the direct C(sp2)-H cyanation of allenes.
- To overcome the inherent difficulties associated with allenic HAA and functionalization.
Main Methods:
- Copper-catalyzed direct C(sp2)-H cyanation of allenes.
- Utilized steric N-fluoro-N-alkylsulfonamide as a hydrogen atom abstractor precursor.
- Investigated the reaction with various tri-, di-, and mono-substituted allenes.
Main Results:
- Achieved exceptional site-selectivity in the cyanation of tri- and di-substituted allenes.
- Successfully cyanated mono-substituted allenes, although with lower yields.
- Demonstrated the crucial role of the steric N-fluoro-N-alkylsulfonamide in directing regioselectivity and preventing undesired radical addition.
Conclusions:
- Developed a novel and efficient copper-catalyzed strategy for allenic C(sp2)-H cyanation.
- The method offers a valuable tool for selective functionalization of allenes.
- The steric properties of the hydrogen atom abstractor are key to the reaction's success.
![[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
01:31Radical Substitution: Allylic Chlorination
2.3K
Typically, when alkenes react with halogens at low temperatures, an addition reaction occurs. However, upon increasing the temperature or under reaction conditions that form radicals, providing a low but steady concentration of halogen radicals, allylic substitution reaction is favored. This is because allylic hydrogens are very reactive as the formed intermediate is resonance stabilized. For example, when propene is treated with chlorine in the gas phase at 400 °C, it undergoes allylic...
2.3K
01:27Radical Substitution: Allylic Bromination
5.1K
In organic synthesis, the formation of products can be altered by changing the reaction conditions. For example, a dibromo addition product is formed when propene is treated with bromine at room temperature. In contrast, propene undergoes allylic substitution in non-polar solvents at high temperatures to give 3-bromopropene. In order to avoid the addition reaction, the bromine concentration must be kept as low as possible throughout the reaction. This can be achieved using N-bromosuccinimide...
5.1K
00:47Radical Formation: Addition
1.7K
Radicals can be formed by adding a radical to a spin-paired molecule. This is typically observed with unsaturated species, where the addition of a radical across the π bond leads to the production of a new radical by dissolving the π bond. For example, the addition of a Br radical to an alkene yields a carbon-centered radical.
Similar to charge conservation in chemical reactions, spin conservation is implicit for radical reactions. Accordingly, the product formed must possess an...
Similar to charge conservation in chemical reactions, spin conservation is implicit for radical reactions. Accordingly, the product formed must possess an...
1.7K
01:17Radical Anti-Markovnikov Addition to Alkenes: Mechanism
3.8K
The reaction of hydrogen bromide with alkenes in the presence of hydroperoxides or peroxides proceeds via anti-Markovnikov addition. The radical chain reaction comprises initiation, propagation, and termination steps.
The mechanism starts with chain initiation, which involves two steps. In the first chain initiation step, a weak peroxide bond is homolytically cleaved upon mild heating to form two alkoxy radicals. In the second initiation step, a hydrogen atom is abstracted by the alkoxy...
The mechanism starts with chain initiation, which involves two steps. In the first chain initiation step, a weak peroxide bond is homolytically cleaved upon mild heating to form two alkoxy radicals. In the second initiation step, a hydrogen atom is abstracted by the alkoxy...
3.8K
02:24Reduction of Alkynes to cis-Alkenes: Catalytic Hydrogenation
7.7K
Introduction
Like alkenes, alkynes can be reduced to alkanes in the presence of transition metal catalysts such as Pt, Pd, or Ni. The reaction involves two sequential syn additions of hydrogen via a cis-alkene intermediate.
Like alkenes, alkynes can be reduced to alkanes in the presence of transition metal catalysts such as Pt, Pd, or Ni. The reaction involves two sequential syn additions of hydrogen via a cis-alkene intermediate.
7.7K
01:16Radical Reactivity: Nucleophilic Radicals
2.1K
Radicals adjacent to electron-donating groups are called nucleophilic radicals. These radicals readily react with electrophilic alkenes. The SOMO–LUMO interactions are the driving force for the reaction, where the high-energy SOMO of the electron-rich, nucleophilic radicals interacts with the low-energy LUMO of the electron-deficient, electrophilic alkenes. Such SOMO–LUMO interactions are the basis of reactive radical traps, affecting the selectivity in radical reactions. For...
2.1K