Three-component cascade carbopalladation/Heck cyclization/borylation: facile access to boryl-functionalized indenes

Area of Science:

• Organic Chemistry
• Catalysis
• Synthetic Methodology

Background:

• Palladium-catalyzed reactions are crucial in modern organic synthesis.
• Developing efficient methods for constructing complex cyclic structures like indenes remains an active research area.
• Introducing boron functionalities into organic molecules enables diverse downstream transformations.

Purpose of the Study:

• To develop a novel, mild, and efficient three-component cascade reaction for synthesizing borylated indene skeletons.
• To explore the scope and limitations of the reaction with various boron reagents.
• To demonstrate the synthetic utility of the borylated indenes through further transformations.

Main Methods:

• A palladium-catalyzed three-component cascade reaction involving o-iodostyrenes, internal alkynes, and boron reagents.
• The reaction proceeds through a sequence of intermolecular carbopalladation, intramolecular Heck-type cyclization, and borylation.
• Utilized various boron sources including bis(pinacolato)diboron ((Bpin)2), bis(neopentyl glycolato)diboron ((Bneop)2), and bis(pinacolato)methanediboron (CH2(Bpin)2).

Main Results:

• Successfully synthesized versatile boryl-functionalized indene skeletons with high selectivity.
• Demonstrated tolerance of different boron sources, including (Bpin)2, (Bneop)2, and CH2(Bpin)2.
• Confirmed the synthetic utility through gram-scale synthesis and subsequent functional group transformations.

Conclusions:

• The developed Pd-catalyzed cascade reaction provides a mild and efficient route to borylated indenes.
• The method is versatile, tolerating various boron reagents and enabling further synthetic elaborations.
• This approach offers a valuable tool for accessing complex organic molecules with potential applications in medicinal chemistry and materials science.