Cyclic Dinucleotide-Based Enantioselective Fluorination in Water
Xingchen Dong1, Shuting Lv1, Qianqian Qi1
1Key Laboratory of Applied Surface and Colloid Chemistry, Ministry of Education, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an710119, China.
The Journal of Organic Chemistry
|December 22, 2022
Summary
A novel cyclic di-AMP and copper catalyst enables efficient enantioselective fluorination in water. This nucleotide-based catalyst offers insights into catalytic mechanisms and structure-activity relationships for asymmetric synthesis.
Area of Science:
- Supramolecular Chemistry
- Catalysis
- Organic Chemistry
Background:
- DNA-based catalysts offer chiral scaffolds but complex structures hinder mechanism elucidation.
- Nucleotide-based catalysts provide simpler designs for understanding structure-activity relationships.
Purpose of the Study:
- To develop a nucleotide-based catalyst for enantioselective fluorination.
- To investigate the host-guest interactions and catalytic mechanism of the assembled catalyst.
Main Methods:
- Assembly of cyclic di-AMP (c-di-AMP) with 1,10-phenanthroline copper(II) nitrate (Cu(phen)(NO3)2).
- Spectroscopic analyses (UV-Vis, fluorescence, CD, NMR) to study host-guest interactions.
- Kinetic studies to evaluate catalytic activity and rate enhancement.
Main Results:
- The c-di-AMP/Cu(phen)(NO3)2 catalyst achieved high yields (90-99%) and enantioselectivity (up to 90% ee) in fluorination reactions in water.
- Spectroscopic data confirmed supramolecular interactions between c-di-AMP and Cu(phen)(NO3)2, with a binding constant of 1.7 ± 0.3 × 10^5 M^-1.
- The catalyst assembly demonstrated a modest rate enhancement for carbon-fluorine bond formation.
Conclusions:
- A c-di-AMP-based supramolecular catalyst enables efficient and enantioselective fluorination in aqueous media.
- The study provides valuable insights into the structure-activity relationship of nucleotide-based asymmetric catalysts.
- This approach offers a promising strategy for designing novel catalysts for organic synthesis.
More Related Videos
Related Concept Videos
01:13Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene
6.3K
Bromination and chlorination of aromatic rings by electrophilic aromatic substitution reactions are easily achieved, but fluorination and iodination are difficult to achieve. Fluorine is so reactive that its reaction with benzene is difficult to control, resulting in poor yields of monofluoroaromatic products. To address this, Selectfluor reagent is used as a fluorine source in which a fluorine atom is bonded to a positively charged nitrogen.
6.3K
02:34Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration
8.6K
The rate of acid-catalyzed hydration of alkenes depends on the alkene's structure, as the presence of alkyl substituents at the double bond can significantly influence the rate.
8.6K
02:41Formation of Halohydrin from Alkenes
13.2K
An alkene, such as propene, reacts with bromine in the presence of water to yield a halohydrin. Halohydrins contain a halogen and a hydroxyl group attached to adjacent carbons. When the halogen is bromine, it is called a bromohydrin, while a chlorohydrin has chlorine as the halogen.
13.2K
01:21Acid-Catalyzed α-Halogenation of Aldehydes and Ketones
4.0K
By replacing an α-hydrogen with a halogen, acid-catalyzed α-halogenation of aldehydes or ketones yields a monohalogenated product
In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a...
In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a...
4.0K
02:46Halogenation of Alkenes
16.1K
Halogenation is the addition of chlorine or bromine across the double bond in an alkene to yield a vicinal dihalide. The reaction occurs in the presence of inert and non-nucleophilic solvents, such as methylene chloride, chloroform, or carbon tetrachloride.
Consider the bromination of cyclopentene. Molecular bromine is polarized in the proximity of the π electrons of cyclopentene. An electrophilic bromine atom adds across the double bond, forming a cyclic bromonium ion intermediate.
Consider the bromination of cyclopentene. Molecular bromine is polarized in the proximity of the π electrons of cyclopentene. An electrophilic bromine atom adds across the double bond, forming a cyclic bromonium ion intermediate.
16.1K
01:20Diazonium Group Substitution with Halogens and Cyanide: Sandmeyer and Schiemann Reactions
2.0K
Arenediazonium substitution reactions occur when the diazonium group is substituted by various functional groups such as halides, hydroxyl, nitrile, etc. For instance, arenediazonium salts react with copper(I) salts of chloride, bromide, or cyanide to form corresponding aryl chlorides, bromides, and nitriles. These reactions are named Sandmeyer reactions. Although the mechanism of this reaction is complicated, as illustrated in Figure 1, they are believed to progress via an aryl copper...
2.0K