Amidolithium and amidoaluminum catalyzed synthesis of substituted guanidines: an interplay of DFT modeling and experiment.
The synthesis of substituted guanidines is of significant interest for their use as versatile ligands and for the synthesis of bioactive molecules. Lithium amides supported by tetramethylethylenediamine have recently been shown to catalyze the guanylation of amines with carbodiimide. In this report, density functional theory (DFT) calculations are used to provide insight into the mechanism of this transformation. The mechanism identified through our calculations is a carbodiimide insertion into the lithium-amide bond to form a lithium guanidinate, followed by a proton transfer from the amine. The proton transfer transition state requires the dissociation of one of the chelating nitrogen centers of the lithium guanidinate, proton abstraction from the amine, and bond formation between the lithium center and the amine nitrogen. On the basis of this mechanism, further calculations predicted that aluminum amides would also function as active catalysts for the guanylation of amines. We confirm this experimentally and report the development of aluminum amides as a new main group catalyst for the guanylation of a range of electron-poor amines with carbodiimide.
Rowley
Christopher N
CN
Centre for Catalysis Research and Innovation, Department of Chemistry, University of Ottawa, Ontario, Canada, K1N 6N5.
Ong
Tiow-Gan
TG
Priem
Jessica
J
Woo
Tom K
TK
Richeson
Darrin S
DS
D002234:Carbodiimides / Q000737:chemistry; D002384:Catalysis; D004583:Electrons; D019791:Guanidine / Q000138:chemical synthesis* / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry*; D011522:Protons; D011789:Quantum Theory
D002234:Carbodiimides; D009942:Organometallic Compounds; D011522:Protons; D019791:Guanidine