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Related Concept Videos

Base-Catalyzed Ring-Opening of Epoxides02:26

Base-Catalyzed Ring-Opening of Epoxides

10.0K
Due to their highly strained structures, epoxides can readily undergo ring-opening reactions through nucleophilic substitution, either in the presence of an acid or a base. The nucleophilic substitution reactions in the presence of acid are called acid-catalyzed ring-opening reactions, and nucleophilic substitution reactions in the presence of a base are called base-catalyzed ring-opening reactions. Epoxides undergo base-catalyzed ring-opening reactions in the presence of a strong nucleophile...
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Acid-Catalyzed Ring-Opening of Epoxides02:24

Acid-Catalyzed Ring-Opening of Epoxides

8.6K
Epoxides that are three-membered ring systems are more reactive than other cyclic and acyclic ethers. The high reactivity of epoxides originates from the strain present in the ring. This ring strain acts as a driving force for epoxides to undergo ring-opening reactions either with halogen acids or weak nucleophiles in the presence of mild acid. The acid catalyst converts the epoxide oxygen, a poor leaving group, into an oxonium ion, a better leaving group, making the reaction feasible. The...
8.6K
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH301:11

ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3

7.2K
All ortho–para directors, excluding halogens, are activating groups. These groups donate electrons to the ring, making the ring carbons electron-rich. Consequently, the reactivity of the aromatic ring towards electrophilic substitution increases. For instance, the nitration of anisole is about 10,000 times faster than the nitration of benzene. The electron-donating effect of the methoxy group in anisole activates the ortho and para positions on the ring and stabilizes the corresponding...
7.2K
Nucleophilic Aromatic Substitution: Elimination–Addition01:11

Nucleophilic Aromatic Substitution: Elimination–Addition

5.0K
Simple aryl halides do not react with nucleophiles. However, nucleophilic aromatic substitutions can be forced under certain conditions, such as high temperatures or strong bases. The mechanism of substitution under such conditions involves the highly unstable and reactive benzyne intermediate. Benzyne contains equivalent carbon centers at both ends of the triple bond, each of which is equally susceptible to nucleophilic attack. This 50–50 distribution of products is...
5.0K
Olefin Metathesis Polymerization: Ring-Opening Metathesis Polymerization (ROMP)01:16

Olefin Metathesis Polymerization: Ring-Opening Metathesis Polymerization (ROMP)

3.1K
Ring-opening metathesis polymerization or ROMP involves strained cycloalkenes as starting materials. The mechanism of ROMP proceeds by reacting cycloalkene with Grubbs catalyst to give metallacyclobutane intermediate which undergoes a ring-opening reaction to form new carbene. The new carbene reacts with another molecule of cycloalkene. Repetition of these steps leads to the formation of an unsaturated open-chain polymer product. All these steps are reversible, however, relieving the ring...
3.1K
Nucleophilic Aromatic Substitution: Addition–Elimination (SNAr)01:30

Nucleophilic Aromatic Substitution: Addition–Elimination (SNAr)

4.6K
Nucleophilic substitution in aromatic compounds is feasible in substrates bearing strong electron-withdrawing substituents positioned ortho or para to the leaving group. The reaction proceeds via two steps: the addition of the nucleophile and the elimination of the leaving group.
The reaction begins with an attack of the nucleophile on the carbon that holds the leaving group. This results in the delocalization of the π electrons over the ring carbons. The resonance interaction between...
4.6K

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Related Experiment Video

Updated: Jan 10, 2026

Controlled Photoredox Ring-Opening Polymerization of O-Carboxyanhydrides Mediated by Ni/Zn Complexes
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A General Approach for Strained Ring Functionalization via Nucleophilic Catalysis.

Ping Wang1,2, Cheng Deng3, Zihao Luo3

  • 1Eastern Institute for Advanced Study, Eastern Institute of Technology, Ningbo, Zhejiang 315200, P. R. China.

JACS Au
|November 28, 2025
PubMed
Summary
This summary is machine-generated.

This study introduces a novel nucleophilic catalysis strategy for reactions with strained rings. It enables direct, diastereoselective addition of diverse C-H bonds and heteroatom nucleophiles without external bases, expanding synthetic possibilities.

Keywords:
base-freebioisoterescovalent intermediatediastereocontrolnucleophilic additionnucleophilic catalysissp3 C–H bondsstrained rings

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Area of Science:

  • Organic Chemistry
  • Synthetic Chemistry
  • Catalysis

Background:

  • Nucleophilic addition to strained rings is crucial for synthesizing small aliphatic rings used as bioisosteres in drug discovery.
  • Existing methods often necessitate stoichiometric bases, additives, or harsh nucleophiles, restricting reaction scope and practicality.
  • Achieving diastereocontrol and directly functionalizing inert sp³ C-H bonds remain significant challenges in this field.

Purpose of the Study:

  • To develop a novel nucleophilic catalysis strategy for the direct and diastereoselective addition of nucleophiles to strained rings.
  • To overcome limitations of existing methods, including the need for external bases and the difficulty of C-H bond functionalization.
  • To broaden the scope of nucleophiles and C-H bonds amenable to reactions with strained ring systems.

Main Methods:

  • Development of a nucleophilic catalysis approach utilizing a catalyst that forms a covalent intermediate with the strained ring.
  • Application of the catalytic system for the direct addition of various sp³ C-H bonds and heteroatom nucleophiles (carboxylic acids, amides, phosphine oxides, thiols).
  • Investigation of reaction mechanisms through mechanistic studies to elucidate the role of the covalent intermediate.

Main Results:

  • Demonstration of a general and efficient nucleophilic catalysis strategy for strained ring functionalization.
  • Successful direct and diastereoselective addition of a wide range of sp³ C-H bonds and heteroatom nucleophiles.
  • Elimination of the requirement for external bases or additives, enhancing reaction practicality and compatibility.
  • Identification of a key covalent intermediate in the catalytic cycle.

Conclusions:

  • The developed nucleophilic catalysis strategy provides an unprecedented route for the direct and diastereoselective functionalization of strained rings.
  • This method significantly expands the scope of nucleophilic addition reactions to strained rings, including challenging C-H bond additions.
  • The findings offer a practical and versatile tool for synthesizing valuable small aliphatic rings and bioisosteres in drug development.