Pd-Catalyzed Cascade Heck/C(sp³)-H Activation for Spirocyclopropyl Oxindoles

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Oxindole derivatives are prevalent in natural products and pharmaceuticals.
• Efficient synthesis of spirocyclic compounds remains a challenge in organic chemistry.

Purpose of the Study:

• To develop a novel catalytic cascade reaction for the synthesis of spirocyclopropyl oxindoles.
• To explore the utility of C(sp3)-H activation in constructing complex oxindole scaffolds.

Main Methods:

• Palladium(0)-catalyzed Heck/C(sp3)-H activation cascade reaction.
• Utilized ortho-bromoacrylamides as starting materials.
• Investigated microwave irradiation for accelerated reaction times.

Main Results:

• Achieved high yields of spirocyclopropyl oxindoles via an unconventional four-membered palladacycle intermediate.
• Demonstrated broad substrate scope and high efficiency with low palladium catalyst loading (0.5 mol %).
• Successfully coupled the spirocyclopropanation with [3 + 2] cycloaddition to yield spiropyrrolidine oxindoles.

Conclusions:

• Established a versatile and efficient Pd(0)-catalyzed method for synthesizing spirocyclopropyl oxindoles.
• The developed strategy provides a valuable pathway for the preparation of complex alkaloids like (±)-horsfiline and (±)-coerulescine.
• Highlights the potential of C(sp3)-H activation in cascade reactions for constructing intricate molecular architectures.