Synthesis of Cyclic Amidines via Ru-Catalyzed Hydroamination

Significance

A Ru-catalyzed synthesis of cyclic amidines by the tandem reaction of aminoalkynes and tosylazides is reported. Ru(0,III), Pd(II), Pt(II), Au(III) and Cu(I) catalyze this reaction, among which, Ru₃(CO)₁₂ demonstrates high efficiency. This reaction tolerates the presence of a variety of electron-withdrawing groups R¹. Interestingly, when n = 1, A is the major product, while B is preferentially formed when n = 2. Because the exo-methylene pyrrolidine is more stable than its endo-isomer, the former reacts less readily than its endo counterpart. A mechanism is postulated involving pathway A and pathway B routes to amidines which is supported by the fact that treatment of 1-benzyl-2-methylenepyrrolidine with TsN₃ under the same reaction conditions results in the formation of a mixture of the same amidines. Furthermore, in a D-labeled experiment (the nitrogen and terminal alkyne were labeled), D-incorporation was observed at both migrated Me and C3 of the piperidine ring. Finally, the evolution of CH₂N₂ was demonstrated by a trapping experiment with PhCO₂H.