Ring expansions of acyloxy nitroso compounds

Area of Science:

• Organic Chemistry
• Synthetic Chemistry

Background:

• Cyclic ketones are common starting materials in organic synthesis.
• Ring expansion reactions are crucial for generating novel molecular scaffolds.
• Hydroxamic acids and lactams are important functional groups in medicinal chemistry.

Purpose of the Study:

• To explore the synthetic utility of acyloxy nitroso compounds derived from cyclic ketones.
• To investigate the regioselectivity of ring expansion reactions.
• To demonstrate the formation of cyclic hydroxamic acids and lactams.

Main Methods:

• Treatment of cyclopentanone and cyclobutanone oximes with lead (IV) tetraacetate.
• Basic hydrolysis of intermediate acyloxy nitroso compounds.
• Reaction of acyloxy nitroso compounds with phosphines.

Main Results:

• Formation of bright blue acyloxy nitroso compounds.
• Successful ring expansion to cyclic hydroxamic acids in yields of 12-81%.
• Regioselective insertion of the -NOH group to the more substituted position in substituted cyclopentanones.
• Generation of ring-expanded Beckmann rearrangement products (lactams) upon reaction with phosphines.

Conclusions:

• Acyloxy nitroso compounds are versatile intermediates for synthesizing cyclic hydroxamic acids and lactams.
• The described method offers a regioselective route to ring-expanded products.
• This chemistry provides access to structurally complex molecules from simple cyclic ketones.