Ureate Titanium Catalysts for Hydroaminoalkylation: Using Ligand Design to Increase Reactivity and Utility

Abstract

Hydroaminoalkylation describes the atom-economical catalytic synthesis of amines by forming new Csp3 –Csp3 bonds using readily available amine and alkene feedstocks. Herein, we describe an earth-abundant and cost-efficient titanium catalyst generated in situ using commercially available Ti­(NMe2)4 and a simple to synthesize urea proligand. This system demonstrates high TOFs for hydroaminoalkylation with unactivated substrates and features easy to use commercially available titanium amido precursors. Additionally, a high catalytic activity, scope of reactivity, and regioselectivity are all demonstrated in the transformation of unactivated terminal olefins with various alkyl and aryl secondary amines. Finally, syntheses of useful amine-containing monomers suitable for the generation of amine-containing materials, as well as amine-containing building blocks for medicinal chemistry, are disclosed. These preparative methods avoid the necessity of glovebox techniques and are modified to be useful to all synthetic chemists.

Reversible C–H Activation in Zirconaaziridine Species: Characterization and Bonding of a Bridging (Amino)alkylidene Complex Active in Alkyne Hydroaminoalkylation

“…While there are a few examples of late-transition-metal complexes with the aziridine binding motif, − the vast majority of isolated examples contain hard Lewis acidic early transition metals with bonding motifs most consistent with the metallaaziridine formulation . The latter variant is particularly interesting because these complexes can be used as α-amino carbanion equivalents, as opposed to π-bound electrophiles, to access a variety of α-substituted nitrogen-containing molecules in stoichiometric or catalytic transformations involving unsaturated molecules. − For example, metallaaziridine species are key intermediates in early-transition-metal-catalyzed hydroaminoalkylation reactions, where the α-C–H bond of an amine is added across an unsaturated C–C bond of an alkene − or an alkyne , in a 100% atom-economical fashion (see Scheme b).…”

Tantalum Ureate Complexes for Photocatalytic Hydroaminoalkylation

“…Also, less toxic and less expensive early-transition metals (ETM) from groups 3, 4 and 5, including earth abundant metals like titanium can be used as catalysts. [22][23][24][25][26] In recent years this strategy has proven to be an efficient, thermally promoted reaction. However, like many other C-H functionalization reactions, this transformation often requires very high reaction temperatures of up to 180 °C.…”

Direct, Catalytic α-Alkylation of N-Heterocycles by Hydroaminoalkylation: Substrate Effects for Regiodivergent Product Formation

“…Our group recently showed that highly active tantalum and titanium ureate hydroaminoalkylation catalysts can be prepared in situ for the efficient alkylation of both aryl and alkyl N -methylated secondary amines. − Although reactivity with N -heterocycles was not achieved, this earlier work showcased the tunable nature of ureate ligand salts to improve catalytic activity and enhance substrate scope. Here, we report a tantalum ureate catalyst for the rapid α-C–H alkylation of saturated N -heterocycles with activated and unactivated alkene coupling partners (Figure c).…”