A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Flow Chemistry

Background:

• Chloramines are versatile reagents but suffer from instability, complicating their isolation and handling.
• The inherent hazards associated with unstable chloramine reagents limit their practical synthetic applications.

Purpose of the Study:

• To develop a safe and efficient continuous-flow methodology for the in situ generation and immediate utilization of N-chloramines.
• To circumvent the challenges of isolating and handling unstable chloramine intermediates in organic synthesis.

Main Methods:

• A continuous-flow reactor system was employed for the generation and subsequent reaction of N-chloramines.
• N-chloramines were synthesized via reactions involving styrenes or directly from N-alkyl/N,N'-dialkyl-N-chloramines.
• Subsequent transformations included reactions with anisaldehyde and base, followed by asymmetric reduction.

Main Results:

• The continuous-flow approach successfully generated and reacted N-chloramines, avoiding isolation.
• The method yielded 2-chloramines from styrenes and amides from anisaldehyde reactions.
• Primary and secondary imines were formed, with one example achieving 94% enantiomeric excess (ee) after asymmetric reduction.

Conclusions:

• The developed continuous-flow method offers a safer and more practical alternative for utilizing unstable N-chloramine reagents.
• This approach expands the synthetic utility of N-chloramines, enabling efficient access to diverse organic molecules.
• The methodology demonstrates potential for scalable and controlled synthesis of complex nitrogen-containing compounds.