Rhodium-Catalyzed Chemo-Divergent Reaction between Oxetan-3-ones/Azetidin-3-ones and Arylboronic Acids

Area of Science:

• Organic Chemistry
• Catalysis
• Medicinal Chemistry

Background:

• Small-ring systems like oxetanes and azetidines are important scaffolds in medicinal chemistry.
• Developing efficient catalytic methods for functionalizing these rings is crucial for drug discovery.
• Existing methods often require stoichiometric reagents or specialized precursors.

Purpose of the Study:

• To develop a versatile rhodium-catalyzed chemo-divergent reaction for oxetan-3-one and azetidin-3-ones.
• To achieve selective synthesis of different product classes (tertiary alcohols or alpha-oxy/amino ketones) through catalyst and temperature control.
• To provide a method that bypasses stoichiometric organometallic reagents and offers broad functional group tolerance.

Main Methods:

• Rhodium-catalyzed reaction of oxetan-3-one and azetidin-3-ones with arylboronic acids.
• Utilizing ligand and temperature control to direct chemo-selectivity.
• Investigating reaction mechanisms including direct carbonyl addition and beta-carbon elimination-initiated ring opening.

Main Results:

• Selective synthesis of tertiary alcohols (3-aryl oxetanols/azetidinols) via carbonyl addition.
• Selective synthesis of alpha-oxy/alpha-amino ketones via beta-carbon elimination.
• Demonstrated broad functional group tolerance and efficient access to carboxylic acid bioisosteres.
• Established a versatile catalytic platform for small-ring system diversification.

Conclusions:

• A novel rhodium-catalyzed chemo-divergent reaction for oxetan-3-one and azetidin-3-ones has been developed.
• The methodology allows for selective access to valuable chemical motifs through simple control of reaction conditions.
• This catalytic platform offers an efficient and versatile approach for synthesizing drug-like molecules and expanding chemical space in drug discovery.