Strained Aza-Heterocycles in Synthesis

“Strain” in organic molecules is a powerful driving force able to promote reactivity through “strain-release”. This concept of strain is often wrongly associated with the idea of instability and cumbersome synthetic routes to access strained molecules, but kinetic and thermodynamic worlds ignore each other since strained molecules can be perfectly stable while highly reactive in a “designed” reaction. On the other hand, nitrogen heterocycles are ubiquitous and can be found in almost 60% of the 200 top-selling drugs, so that new synthetic tools for their preparation is a hot topic, and source of continuous innovation.

The research topic « strained aza-heterocycles in synthesis » aims at gathering papers reporting the use of three and four-membered aza heterocycles, (ie: aziridines, azetidines, azetidinones) as well as their activated forms (aziridinium and azetidiniums), or their unsaturated forms (azirines and azetines) in synthesis. The inherent strain in these species (whose list is not restricted to cited ones) is the driving force to promote various new synthetic methodologies, such as ring expansions, ring opening, domino processes… that have gained increasing attention over past years, and some have become powerful tools that can be used in total synthesis as elegant key-steps or as innovative tools in diversity-oriented-synthesis.

Papers reporting such methodologies, as well as new optimized synthetic routes to these strained heterocycles, would be welcome, together with papers analyzing fundamental aspects of the mechanism of the highly diverse reactions involved in strain-release.