Titanium-catalyzed iminohydrazination of alkynes

Titanium pyrrolyl complexes Ti(NMe2)2(dap)2 (1), where dap is 2-(N,N-dimethylaminomethyl)pyrrolyl, and Ti(NMe2)3(bap) (3), where bap is 2,5-bis(N,N-dimethylaminomethyl)pyrrolyl, were found to be effective catalysts for the iminohydrazination of alkynes, a new multicomponent coupling reaction involving an alkyne, hydrazine, and isonitrile. A brief study on the scope of the reaction suggests that it is applicable to internal and terminal alkynes, alkyl and aryl isonitriles, and alkyl- and aryl-containing 1,1-disubstituted hydrazines. The best yields were obtained with terminal alkynes and alkyl isonitriles. The regioselectivity of the reactions is quite sensitive to catalyst structure, and, in all cases, we were able to obtain one regioisomer of the iminohydrazination product with either 1 or 3 as catalyst. The conformation of the products was probed by NMR spectroscopy and DFT calculations, which suggest that the s-cis isomer of the hydrazone–enamine tautomer is the most favorable configuration. However, several configurations are probably accessible in solution at room temperature. Reaction of 1 with 2 equivalents of H2NNMe2 results in the formation of a dinuclear complex Ti2(dap)3(NNMe2)2(NHNMe2) (4), where one dap ligand was removed protolytically. Examination of regioselectivities in iminohydrazination reactions using 4 and mono(dap) complex Ti(dap)(NMe2)3 (5) are consistent with these species using the same catalytic cycle as 1. Consequently, the active species is likely a mono(dap) titanium complex. Current mechanistic information is consistent with a hydrazido(2−) intermediate and a pathway reminiscent of the Bergman hydroamination mechanism. Ti(NMe2)3(bap) (3) and Ti2(dap)3(NNMe2)2(NHNMe2) (4) were characterized by X-ray diffraction.

Titanium pyrrolyl complexes are effective catalysts for a new multicomponent coupling reaction between hydrazines, isonitriles, and alkynes. The products of the formal iminohydrazination reaction are 1,3-hydrazonylimines, and the regioselectivity of the reaction is quite sensitive to the catalyst structure. Studies concerning the mechanism of the reaction and some potential intermediates are discussed.Figure optionsDownload as PowerPoint slide