Ti-catalyzed 1,2-Diamination of Alkynes Using 1,1-Disubstituted Hydrazines

Ti-catalyzed alkyne diamination and alkyne hydrohydrazination proceed through a common N-aminoazatitanacyclobutene intermediate. These reactions have historically existed as processes catalyzed by distinct molecular Ti compounds, with several reports for hydrohydrazination and only a single example for diamination. Here, we demonstrate that a diamidoamine Ti catalyst, (NNN)Ti(═NNR₂) (1, (NNN)H₂ = N-methyl-N',N″-bis(trimethylsilyl)diethylenetriamine; R = alkyl, aryl), is capable of catalyzing both diamination and hydrohydrazination, where the selectivity is dictated by simple changes to the reaction conditions. This approach capitalizes on the fact that there are entropic differences at the selectivity branch point between diamination (unimolecular) and hydrohydrazination (bimolecular). This discovery leads to an expanded substrate scope for alkyne diamination and provides an understanding of how structure-activity relationships can impact the relative rates (selectivity) of diamination and hydrohydrazination. These structure-activity relationships, anchored on ¹⁵N NMR descriptors, were then used to design a novel, highly active, and selective diamination catalyst, (NNN^SiMe2Ph)Ti(═NNR₂) (1f), which contains bulkier flanking amide ligands. More broadly, these results suggest that this strategy may be applied more generally to Ti hydrohydrazination catalysts to uncover new catalysts capable of alkyne diamination with 1,1-disubstituted hydrazines.