Our lab at the University of Toronto is involved in chemical synthesis with a particular emphasis on creating novel biologically active molecules. From its inception in 1998, our lab has taken a range of directions in organic chemistry, all of which have had fundamental chemical reactivity as the driver. Early on, our efforts to develop chemo- and stereoselective processes involved synthetic electrochemistry, fluorine chemistry, and metal catalysis. Our current efforts are aimed at developing novel chemoselective reactions. One of the appealing approaches towards new chemoselective reactions is to search for building blocks containing multiple functional groups with orthogonal chemical reactivity. In this regard, amphoteric molecules possessing nucleophilic and electrophilic sites offer a versatile platform for the development of chemoselective transformations.
As part of a program aimed at establishing new methods of synthesis, our research has been focused on the development of amphoteric reagents. In the course of our research, we have prepared and evaluated aziridine aldehydes, a class of stable unprotected α-amino aldehydes. Structurally, aziridine aldehydes are amphoteric molecules equipped with nucleophilic amine nitrogen and electrophilic aldehyde carbon over the span of three atoms. Under ambient conditions, aziridine aldehydes exist as homochiral dimers with an aziridine-fused five-membered cyclic hemiaminal structure. Chemoselective functionalization of aziridine aldehydes involving both the aziridine and aldehyde functionality has been investigated. A wide range of densely functionalized nitrogen-containing compounds has been made. We also developed air- and moisture-stable α-boryl aldehydes, which exemplify another class of kinetically amphoteric molecules. The α-boryl aldehydes contain a tetracoordinated N-methyliminodiacetic acid (MIDA) boryl substituent, which stabilizes the amphoteric alpha-metalloid carbonyl system and prevents it from isomerization to its O-bond enolate form. Synthetic applications of α-boryl aldehydes, particularly chemoselective transformations based on the aldehyde functionality, have allowed us to develop a series of new functionalized boron-containing compounds, such as α-borylcarboxylic acids, boryl alcohols, enol ethers, enamides, and other derivatives that are difficult or impossible to prepare using established protocols. All of these compounds are versatile building blocks in their own right, enabling rapid synthesis of boron-containing molecules. Please visit our Sigma page and take a look at our latest amphoteric regents.
We encourage you to visit Andrei’s blog at www.amphoteros.com, for daily updates on other aspects of our work as well as on general organic chemistry. There you will be able to read about the latest in our structural biology projects, which deploy the rich arsenal of methods developed in our lab to identify probes for a wide range of protein targets.