Ti-Catalyzed 1,2-Diamination of Alkynes using 1,1-Disubstituted Hydrazines

Ti-catalyzed alkyne diamination and Ti- catalyzed alkyne hydrohydrazination proceed through a common N-aminoazatitanacyclobutene intermediate. Previously, these reactions have existed as processes catalyzed by distinct catalysts, where there are many reports (and catalysts) for hydrohydrazination, and only a single example (and catalyst) 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, capitalizing on Ph 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 an understanding of how structure-activity relationships can impact the relative rates (selectivity) of diamination and hydrohydrazination. More broadly, these results suggest that this strategy may be more generally applied to Ti hydrohydrazination catalysts to uncover new catalysts capable of alkyne diamination with 1,1-disubstituted hydrazines.