Cyclic Amine Synthesis via Catalytic Radical-Polar Crossover Cycloadditions

Area of Science:

• Organic Chemistry
• Synthetic Methodology
• Catalysis

Background:

• Cyclic amines are crucial structural motifs in pharmaceuticals and natural products.
• Efficient and sustainable synthesis of cyclic amines remains a key challenge in organic chemistry.
• Novel synthetic disconnections are needed to expand access to diverse cyclic amine scaffolds.

Purpose of the Study:

• To report a novel catalytic radical-polar crossover cycloaddition for cyclic amine synthesis.
• To demonstrate the utility of primary sulfonamides as bifunctional reagents in photoredox catalysis.
• To provide an efficient and sustainable method for constructing substituted cyclic amine derivatives.

Main Methods:

• Photoredox catalysis was employed to initiate the reaction.
• A catalytic radical-polar crossover cycloaddition mechanism was utilized.
• Primary sulfonamides served as the key starting materials and radical precursors.

Main Results:

• The developed method enables the efficient synthesis of cyclic amines in a single step.
• The approach allows for the construction of both β, β-disubstituted and β-monosubstituted cyclic amines.
• The methodology exhibits broad functional group tolerance, including with drug derivatives and natural products.

Conclusions:

• Primary sulfonamides are unique bifunctional reagents, acting as both radical precursors and nucleophiles.
• This photoredox-catalyzed reaction offers a sustainable and economically viable route to valuable cyclic amines.
• The developed synthetic disconnection expands the toolkit for accessing complex cyclic amine architectures.