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The core of achieving asymmetric nucleophilic aromatic substitution (SNAr) reactions lies in **chiral control**. Common strategies include:
### **1. Chiral Auxiliary Group Method**
- **Substrate Modification**: Introduce chiral auxiliary groups (such as oxazolines, sulfonamides) on the aromatic ring to guide the stereospecific attack of nucleophilic reagents (amines, alcohols) (*J. Am. Chem. Soc.* **2005**, _127_, 16422).
- **Example**: The ortho-chiral sulfonamide aryl compound reacts with an amine, achieving configuration control through steric hindrance (*Org. Lett.* **2012**, _14_, 1934).
### **2. Chiral Catalyst Regulation**
- **Phase Transfer Catalysis (PTC)**: Use kavalonol derivatives (such as Maruoka catalysts) to catalyze SNAr of fluorinated aromatics, achieving dynamic kinetic resolution (*Nature* **2018**, _554_, 183).
- **Transition Metal Catalysis**: Activate aryl halides with Pd/hand chiral phosphine ligands to promote asymmetric coupling (*ACS Catal.* **2020**, _10_, 10551).
### **3. Axial Chiral Substrate Utilization**
- **Linked Aromatic Skeleton**: Utilize stereoregular isomers (such as BINOL derivatives) to control the direction of nucleophilic attack through steric hindrance (*Angew. Chem. Int. Ed.* **2019**, _58_, 15795). **Key Points**: It is necessary to combine substrate design (activating groups such as -NO₂, -CF₃) with chiral induction strategies (catalysts/auxiliary groups), and preferentially select electron-deficient aromatic rings to enhance reactivity.
