Enantioselective synthesis of cyclic and linear diamines by imine cycloadditions

Abstract

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.

Conversion of Hydroxyproline “Doubly Customizable Units” to Hexahydropyrimidines: Access to Conformationally Constrained Peptides

“…Hexahydropyrimidines are valuable components of different drugs 4 , 5 and have been usually prepared from a diamine derivative and an aldehyde, 4b , 4c , 5a , 6 although cycloadditions from imines have also been reported. 7 This methodology works well for the preparation of simple hexahydropyrimidines but offers little selectivity when several reactive amine or amide groups are present in the molecule, particularly in complex ones such as peptides. Unlike the classical approach, the present methodology uses a dicarbonyl compound (substrate 5 ) that reacts with an amine (as commented in Schemes 1 and 2 ).…”