Nucleophilic Ring Opening Of Nonracemic Trisubstituted Aziridines And The Application Of The Reaction To The Synthesis Of Ceanothine D

Aziridines are three-membered cyclic heterocycles that contain a nitrogen atom in the ring. The large ring strain associated with aziridines allows them to undergo ring-opening reactions. In the case where the aziridine is unsymmetrical regioselective ring opening may or may not occur. We now present the synthesis of several trisubstituted alkynyl aziridines that underwent regioselective ring opening with amine nucleophiles to produce 1,2-diamines. The regioselectivity of the ring opening appeared to be determined by the transition state energies of the SN2-like ring opening and this assumption was supported by DFT calculations. We also report the stereoselective synthesis of allenes through the use of Normant cuprates and alkynyl aziridines. The first total synthesis of the cyclopeptide alkaloid ceanothine D was achieved using a trisubstituted alkynyl aziridine to install a tertiary alkyl-ether moiety. The macrocyclization was planned by two different methods. One approach using a traditional lactam formation via an activated ester and the other involving an intramolecular aziridine ring opening.