Facile Access to Optically Active 2,6-Dialkyl-1,5-Diazacyclooctanes

Chem Asian J. 2019 Nov 18;14(22):4048-4054. doi: 10.1002/asia.201900938. Epub 2019 Aug 13.


The chiral substituted 1,5-diazacyclooctane (1,5-DACO) is of considerable importance and has attracted attention from a wide range of fields due to their unique chemical and biological properties. Despite the application potential, further study has not been optimized due to difficulties in their synthetic accessibility. Here, we report that the 1,5-DACO bearing a chiral auxiliary obtained from the formal [4+4] cycloaddition of N-alkyl-α,β-unsaturated imines can be further derivatized by nucleophilic alkylation to give various chiral substituted 1,5-DACO derivatives. The removal of the chiral auxiliary was effectively carried out using hydrogenation over Pearlman's catalyst. This methodology allows the production of a broad range of unprecedented optically active 2,6-dialkyl-1,5-DACO, which could not be accessed by other methods.

Keywords: [4+4] cycloaddition; asymmetric synthesis; chiral amines; diazacyclooctane; saturated heterocycles.