A Pd-Catalyzed (6+2) Cycloaddition/Ring-Contraction Relay for Chemodivergent Access to Chiral Spirooxindoles

Area of Science:

• Organic Chemistry
• Catalysis
• Asymmetric Synthesis

Background:

• Indole-fused medium-ring lactones are valuable synthetic targets.
• Developing efficient methods for constructing all-carbon quaternary stereocenters is challenging.

Purpose of the Study:

• To develop a palladium-catalyzed asymmetric (6+2) cycloaddition for indole-fused eight-membered lactones.
• To explore chemodivergent skeletal reorganization of these lactones.

Main Methods:

• Palladium-catalyzed asymmetric (6+2) cycloaddition.
• Modulation of reaction conditions (oxidative vs. basic).
• Density functional theory (DFT) calculations for mechanistic insights.

Main Results:

• Direct synthesis of indole-fused eight-membered lactones with an all-carbon quaternary stereocenter.
• High efficiency and enantioselectivity in the cycloaddition.
• Chemodivergent ring contraction to seven-membered spirooxindoles (oxidative) or six-membered spirooxindoles (basic) with high diastereoselectivity and enantiospecificity.

Conclusions:

• A versatile Pd-catalyzed method for constructing complex indole-fused lactones and spirooxindoles.
• Demonstrated control over skeletal reorganization through simple condition modulation.
• Mechanistic understanding provided by DFT calculations supports the observed reactivity.