A Deep Cavitand Templates Lactam Formation in Water

Area of Science:

• Organic Chemistry
• Supramolecular Chemistry

Background:

• Cyclization reactions exhibit predictable rate dependencies on ring size due to conformational and strain factors.
• Medium-sized rings are challenging to synthesize due to unfavorable conformations and low reaction rates.
• High dilution conditions are typically employed to favor intramolecular cyclization over intermolecular reactions.

Purpose of the Study:

• To investigate the use of cavitands as templates to facilitate the formation of medium-sized lactams from omega-amino acids in aqueous solution.
• To improve the efficiency of intramolecular cyclization reactions in water using supramolecular hosts.

Main Methods:

• Employing cavitands to bind omega-amino acids in pre-organized conformations conducive to cyclization.
• Conducting cyclization reactions in aqueous deuterium oxide (D2O) solution.
• Quantifying yield improvements for specific lactam ring sizes.

Main Results:

• Cavitand templating significantly enhanced the yields of medium-sized lactams.
• A 4.1-fold yield increase was observed for a 12-membered lactam.
• A 2.8-fold yield increase was observed for a 13-membered lactam.

Conclusions:

• Cavitands effectively template intramolecular cyclization reactions in aqueous media.
• This approach facilitates the synthesis of medium-sized lactams, overcoming typical kinetic limitations.
• The findings support the potential for conducting dehydration-involved organic reactions in water using host-guest chemistry.