Accelerated Discovery of Energy Transfer-Catalyzed Dearomative Cycloadditions through a Data-Driven Three-Layer...

Area of Science:

• Photocatalysis
• Organic Synthesis
• Medicinal Chemistry

Background:

• Visible-light photocatalysis enables synthesis of complex 3D molecules from planar heteroarenes.
• Current methods are limited to bicyclic systems, leaving monocyclic heteroarenes underexplored.
• High triplet energy barriers challenge the activation of monocyclic heteroarenes.

Purpose of the Study:

• To develop novel energy transfer (EnT) photocatalysis for intermolecular dearomative cycloadditions of monocyclic heteroarenes.
• To overcome limitations in triplet-state reactivity and accelerate reaction discovery.
• To create new C(sp3)-rich 3D molecular scaffolds.

Main Methods:

• Employed a data-driven, three-layer screening strategy.
• Integrated predictive data science for excited-state properties.
• Utilized luminescence quenching and reaction-based screening.

Main Results:

• Uncovered structure-reactivity relationships between heteroarenes and biradical acceptors.
• Developed EnT-catalyzed cycloadditions of thiophenes, oxazoles, and thiazoles.
• Achieved unprecedented access to C(sp3)-rich 3D molecular scaffolds.

Conclusions:

• The data-driven approach accelerates the discovery of new reactivity in dearomative cycloadditions.
• EnT photocatalysis provides a powerful route to complex 3D molecules from simple heteroarenes.
• This work expands the scope of photocatalytic dearomative functionalization.