New MCR-Heck-isomerization cascade toward indoles

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Indole scaffolds are crucial structural motifs in numerous pharmaceuticals and natural products.
• Efficient and versatile synthetic routes to substituted indoles are highly sought after in drug discovery.

Purpose of the Study:

• To develop a novel, efficient synthetic methodology for accessing indole scaffolds.
• To couple the Ugi-Smiles reaction with Heck cyclization in a streamlined process.

Main Methods:

• Utilized ortho-iodonitrophenol as a key starting material.
• Employed a one-pot sequence combining Ugi-Smiles reaction and Heck cyclization.
• Investigated the neutralization of residual isocyanide prior to palladium catalyst addition.

Main Results:

• Successfully synthesized diverse indole scaffolds through the Ugi-Smiles/Heck cyclization sequence.
• Demonstrated that neutralizing residual isocyanide allows for a seamless one-pot procedure.
• Achieved new access to valuable indole derivatives.

Conclusions:

• The described one-pot methodology offers a powerful and efficient route to indole scaffolds.
• This approach simplifies indole synthesis, making it more accessible for medicinal chemistry applications.
• The strategy highlights the utility of ortho-iodonitrophenol in tandem reactions.