C-H functionalisation of aldehydes using light generated, non-stabilised diazo compounds in flow

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Photochemistry

Background:

• Non-stabilized diazo compounds are highly reactive and difficult to handle, limiting their synthetic applications.
• Previous methods for diazo compound generation and utilization often require harsh conditions or catalysts, restricting functional group tolerance.

Purpose of the Study:

• To develop a safe, efficient, and versatile method for generating and utilizing non-stabilized diazo species.
• To explore the direct, non-catalytic C-H functionalization of aldehydes using bench-stable oxadiazoline precursors.
• To achieve the synthesis of unsymmetrical ketones under mild, additive-free conditions.

Main Methods:

• Utilizing oxadiazolines as bench-stable precursors for non-stabilized diazo species.
• Employing UV photolysis in a flow reactor for in situ generation and reaction of diazo intermediates.
• Performing direct, non-catalytic C-H functionalization of aldehydes without transition metals or additives.

Main Results:

• Successful coupling of commercially available aldehydes to produce unsymmetrical aryl-alkyl and alkyl-alkyl ketones.
• Demonstration of exceptional functional group tolerance due to mild reaction conditions and the absence of transition metal catalysts.
• Scalability of the reaction demonstrated through both small-scale and continuous flow production.

Conclusions:

• Oxadiazolines provide a practical and safe alternative for accessing non-stabilized diazo chemistry.
• The developed flow photolysis method enables direct, metal-free C-H functionalization of aldehydes with broad applicability.
• This approach offers a versatile and scalable route for synthesizing diverse ketone structures with high functional group compatibility.