October 22, 2021
1,2-Dazetidine as new amidomethylative reagent to control the selectivity to synthesis of N-heterocycles and Ru(II) catalyzed enantioselective ortho and meta C–H activation
Chaminda Lakmal Hetti Handi
Department of Chemistry
Mississippi State University
Friday, October 22, 2021
1,2-Diazetidine is a four-membered ring heterocyclic compound which has two adjacent nitrogen atoms. However, the synthesis of C-unsubstituted 1,2-Diazetidines are rarely reported in the literature. C-unsubstituted 1,2-diazetidines were synthesized through an operational simple intermolecular vicinal disubstitution reaction between 1,2-dibromoethane and hydrazine which has N-arylsulfonyl as protecting group. Several different types of C-unsubstituted 1,2-diazetidines derivatives were synthesized with either two same or two different N-arylsulfonyl groups. The electronic and steric properties were analyzed using Raman spectroscopy and computational calculations. There several synthetic applications were demonstrated with 1,2-ditosyl-1,2-Diazetidine (DTD). As a synthetic application, a nucleophilic ring-opening reaction of the diazetidine was identified through a selective cleavage of the N‒N bond by various thiols and it was resulting in the stereoselective formation of a new class of N-sulfenylimine. Furthermore, DTD undergoes FeBr2-catalyzed retro [2+2] ring-opening and sustained releases formaldimine (FI) in situ in a reaction medium which is the simplest imine used as amidomethylative reagent. The effective available concentration can be controlled low in concentration in the reaction medium. Moreover, the sustained release of FI was able to interrupt the amidometylative process with alpha-methylstyrene together with FeBr2 as the catalyst and able to synthesis 4-phenyl-1,2,3,6-tetrahydropyrimidine (PTPH) as a product. The PTPH is a neurotoxic compound that is using as the induces Parkinson’s disease in the animal model. In addition to that sustained release of FI is able to switch the selectivity from alkene, imine, and imine arrangement to alkene, imine, and alkene arrangement in [2+2+2] cycloaddition reaction and lead to form piperidines as a product which is most observed heterocycle in marketed drug molecule.
Chromanes derivatives are observed in pharmaceuticals and natural products. Chiral pure chromane derivatives were synthesized through ruthenium-catalyzed chiral transient directing mediated enantioselective C–H activation. Interestingly phosphate was involved in the deprotonation step which was the rate determining step with a 5.3 KIE value.
Furthermore, 2,2’,2’’-(methoxymethanetriyl)tripyridine (TPy) was synthesized N,N,N-tridentate ligand which coordinates as facial ligand. Ruthenium metallic complex was synthesized, and properties and catalytic meta-C–H activation were evaluated. Furthermore, chiral versions of TPy ligand were synthesized and chiral Ru(II)-complexes were formed for enantioselective meta-C–H activation.