Ir-Catalyzed Asymmetric Synthesis of 3-Allylic Spirotetramic Acid Derivatives with Insecticidal Activities

Area of Science:

• Organic Chemistry
• Catalysis
• Medicinal Chemistry

Background:

• Spirotetramic acid derivatives are important scaffolds in agrochemicals.
• Developing efficient and enantioselective synthetic methods is crucial for discovering new bioactive compounds.

Purpose of the Study:

• To develop novel iridium-catalyzed cascade reactions for synthesizing chiral spirotetramic acid derivatives.
• To establish a sequential catalytic system for constructing complex spirotetramic acid structures with multiple stereocenters.
• To evaluate the insecticidal activity of the synthesized compounds.

Main Methods:

• Iridium-catalyzed allylation/esterification cascade reaction of spirotetramic acid derivatives.
• Sequential iridium- and cinchona alkaloid-catalyzed double allylations.
• Enantioselectivity and diastereoselectivity analysis using chiral chromatography.
• Insecticidal activity assays against Aphis craccivora.

Main Results:

• Chiral 3-allylic spirotetramic acid ester derivatives were obtained with 94-99% enantioselectivity and 43-97% yield.
• Chiral 3-allylic spirotetramic acid derivatives with two stereogenic centers were synthesized with 99% enantioselectivity and moderate to high diastereoselectivity (4:1 to >20:1 dr).
• Compound (S)-4d demonstrated significant insecticidal activity against Aphis craccivora (LC50 = 0.094 g·L-1), outperforming its (R)-enantiomer and racemate.

Conclusions:

• The developed iridium-catalyzed cascade and sequential double allylation reactions provide efficient access to enantiomerically enriched spirotetramic acid derivatives.
• The stereochemistry significantly influences insecticidal activity, highlighting the importance of enantioselective synthesis.
• The synthesized compounds hold potential as novel insecticides.