Air- and moisture-stable amphoteric molecules: enabling reagents in synthesis

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Chemoselective synthesis strategies are crucial for rapidly assembling complex molecules.
• Amphoteric molecules, possessing both nucleophilic and electrophilic sites, offer a versatile platform for developing chemoselective transformations.
• The development of novel building blocks with multiple functional groups and orthogonal reactivity is an ongoing area of research.

Purpose of the Study:

• To highlight examples of amphoteric molecules developed in the lab since 2006.
• To showcase the utility of aziridine aldehydes and alpha-boryl aldehydes in synthesizing functionalized compounds.
• To demonstrate the application of these molecules in creating new boron-containing reagents and complex structures.

Main Methods:

• Preparation and evaluation of stable, unprotected aziridine aldehydes (alpha-amino aldehydes).
• Investigation of chemoselective reactions involving both aziridine and aldehyde functionalities.
• Development and utilization of air- and moisture-stable alpha-boryl aldehydes featuring N-methyliminodiacetyl (MIDA) boryl substituents.

Main Results:

• Aziridine aldehydes, existing as cyclic hemiaminal dimers, undergo chemoselective transformations to yield diverse nitrogen-containing compounds like amino aldehydes, diamines, and macrocyclic peptides.
• Alpha-boryl aldehydes enable the synthesis of novel functionalized boron-containing compounds, including alpha-borylcarboxylic acids and boryl alcohols, which are difficult to access via traditional methods.
• New amphoteric borylated reagents, such as alpha-boryl isocyanates and acylboronates, were synthesized from alpha-borylcarboxylic acids, serving as versatile building blocks.

Conclusions:

• Amphoteric molecules, particularly aziridine aldehydes and alpha-boryl aldehydes, are powerful tools for advancing chemoselective synthesis.
• These reagents facilitate the rapid and efficient construction of complex nitrogen and boron-containing molecules.
• The developed methodologies provide access to novel chemical entities and expand the toolkit for synthetic chemists.