Dual-Pathway Skeletal Editing of Isoquinolines.

Area of Science:

• Organic Chemistry
• Synthetic Chemistry

Background:

• Isoquinoline derivatives are important scaffolds in medicinal chemistry.
• Efficient synthetic routes to complex polycyclic aromatic compounds are highly sought after.

Purpose of the Study:

• To develop a novel dual-pathway skeletal editing strategy for isoquinolines.
• To achieve selective synthesis of naphthalenes and benzo[f]quinazolines from a common intermediate.

Main Methods:

• Activation of isoquinolines using triflic anhydride (Tf2O).
• Reaction of the activated intermediate with secondary amines.
• Orthogonal reaction control using blue-light irradiation or microwave heating.
• Utilizing acetonitrile as a bifunctional C1 synthon.

Main Results:

• Selective N-to-C transmutation under blue-light irradiation yielded naphthalenes.
• Cascade skeletal editing and annulation under microwave heating produced benzo[f]quinazolines.
• Stepwise N-to-C and C-to-C transformations were achieved, enabling rare access to benzo[f]quinazolines.

Conclusions:

• A versatile dual-pathway skeletal editing of isoquinolines was established.
• The method allows for selective synthesis of distinct polycyclic aromatic structures.
• This provides a rare and efficient route to benzo[f]quinazolines.