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, (NNNSiMe2Ph)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.