Synthesis of Sterically Congested Z-Selective Secondary β-Enaminal

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Cyclic ethynylethylene carbonates (EECs) typically undergo copper-allenylidene reactivity.
• Developing alternative reactivity pathways for EECs is crucial for novel synthetic transformations.
• Previous methods often involve harsh conditions or hazardous reagents.

Purpose of the Study:

• To develop a novel copper-catalyzed protocol for EECs.
• To achieve allenal reactivity instead of the classical copper-allenylidene pathway.
• To synthesize Z-selective secondary enaminals with bulky N-aryl groups.

Main Methods:

• Copper-catalyzed reaction of cyclic ethynylethylene carbonates (EECs) with bulky anilines.
• Utilizing sterically induced reactivity switch.
• Employing mild reaction conditions.
• Performing late-stage functionalization.
• Conducting Density Functional Theory (DFT) studies.

Main Results:

• The protocol successfully generated Z-selective secondary enaminals with bulky N-aryl substituents.
• The reaction proceeds via an allenal intermediate, controlled by steric hindrance from anilines.
• The methodology operates under mild conditions and avoids hazardous chemicals.
• Late-stage functionalization demonstrated the potential applications of the synthesized enaminals.
• DFT studies elucidated the origin of Z-selectivity.

Conclusions:

• A novel sterically controlled reactivity switch for EECs has been established, favoring allenal over allenylidene pathways.
• This method provides a mild and safer alternative for synthesizing valuable Z-selective enaminals.
• The developed protocol offers potential for late-stage functionalization in complex molecule synthesis.