Unanticipated Three-Component Cascade and Sequential Cyclization: Highly Diastereoselective Synthesis of...

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Agrochemical Research

Background:

• Developing efficient synthetic strategies for complex carbocycles is crucial in organic chemistry.
• Malononitrile and α,β-unsaturated ketones are versatile building blocks in organic synthesis.
• There is a need for novel antifungal agents to combat phytopathogenic fungi.

Purpose of the Study:

• To develop a novel cascade annulation strategy for constructing polyfunctionalized cyclohexanes.
• To explore the utility of α,β-unsaturated ketones as 2C or 3C synthons in a [1 + 2 + 3] annulation.
• To evaluate the antifungal activity of the synthesized cyclohexane derivatives against phytopathogenic fungi.

Main Methods:

• DBU-catalyzed cascade and sequential [1 + 2 + 3] annulation reaction.
• Utilizing malononitrile as a dinucleophile (1C synthon) and α,β-unsaturated ketones as 2C or 3C synthons.
• In vitro antifungal activity screening of synthesized compounds.

Main Results:

• High yields (>93%) and excellent diastereoselectivity (>19:1 dr) were achieved in the synthesis of polyfunctionalized cyclohexanes.
• A novel one-pot strategy was established for constructing six-membered carbocycles.
• Compound 3l demonstrated broad-spectrum antifungal activity against phytopathogenic fungi.

Conclusions:

• The reported DBU-catalyzed annulation is an efficient method for synthesizing complex cyclohexanes.
• The synthesized compounds hold potential as novel agricultural antifungal agents.
• Compound 3l is a promising candidate for further development as a fungicide.