Enantioselective synthesis of cyclic and linear diamines by imine cycloadditions

Chirality. 2020 Sep;32(9):1160-1168. doi: 10.1002/chir.23265. Epub 2020 Jul 3.


Imine is one of the most versatile functional groups in chemistry and biochemistry fields. Although many biochemical reactions involve imine formation, the inherently unstable property of N-alkyl-α,β-unsaturated imines still hindered their utilization in organic synthesis. In this article, we described that the N-alkyl-α,β-unsaturated imines, which prepared from alkylamines and acrolein, could smoothly react through [4 + 4] cycloaddition to give eight-membered diazacyclooctane derivatives in excellent yields. Under a similar condition, in the presence of formaldehyde, the [4 + 2] and [4 + 2 + 2] cycloadditions could lead to the formation of six-membered hexahydropyrimidine or eight-membered triazacyclooctanes, depending on the substituent of aldehydes. Moreover, an easy functional group manipulation of the cyclic products obtained from these cycloadditions can provide variously substituted chiral linear diamines. We can utilize these novel reactivities to reveal the unknown and essential properties of many biological processes that involve N-alkyl-unsaturated imines.

Keywords: 1,3-diamine; acrolein; cycloaddition; diazacyclooctane; hexahydropyrimidine; triazabicyclononane; triazacyclooctane.