Cyclic Ureate Tantalum Catalyst for Preferential Hydroaminoalkylation with Aliphatic Amines: Mechanistic Insights into Substrate Controlled Reactivity

Abstract

The efficient and catalytic amination of unactivated alkenes with simple secondary alkyl amines is preferentially achieved. A sterically accessible, N,O-chelated cyclic ureate tantalum catalyst was prepared and characterized by X-ray crystallography. This optimized catalyst can be used for the hydroaminoalkylation of 1-octene with a variety of aryl and alkyl amines, but notably enhanced catalytic activity can be realized with challenging N-alkyl secondary amine substrates. This catalyst offers turnover frequencies of up to 60 h–1, affording full conversion at 5 mol% catalyst loading in approximately 20 min with these nucleophilic amines. Mechanistic investigations, including kinetic isotope effect (KIE) studies, reveal that catalytic turnover is limited by protonolysis of the intermediate 5-membered azametallacycle. A Hammett kinetic analysis shows that catalytic turnover is promoted by electron rich amine substrates that enable catalytic turnover. This more active catalyst is shown to be effective for late stage drug modification.

Ni-catalyzed hydroalkylation of olefins with N-sulfonyl amines

“…ompounds featured with a carbon-carbon double bond serve as important precursors for complex aliphatic molecules because of their ready availability and versatility in transition-metal-catalyzed functionalizations [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] . In this respect, advances in nickel-complex-catalyzed hydrocarbonation of olefins have expanded the chemical space of accessible structures and enabled new synthetic disconnections [17][18][19][20][21] .…”

Commodity Polymers to Functional Aminated Materials: Single-Step and Atom-Economic Synthesis by Hydroaminoalkylation

“…HAA is a transition-metal catalyzed, green, amination method that operates by activating the C–H bond α to an amine nitrogen and adding it across a carbon–carbon unsaturation . Advances in HAA catalyst design have enabled the coupling of a broad scope of commercial amines and small molecule alkenes. − Efforts to apply HAA for the functionalization of macromolecules with first generation HAA catalysts showed promise but suffered from long reaction times, of at least 18 h, and were limited to N -methylaniline. − Our group has developed a highly active N , O -chelated tantalum catalyst ( [Ta] , Scheme ), which promotes catalysis in minutes and displays excellent reactivity with both aryl and alkyl amines. Here we show that this improved catalyst is efficient for catalytic postpolymerization amination to prepare functional materials, with no byproduct formation, thereby affording polymers suitable for further synthetic elaboration.…”

“…The amine substrates, N -methylaniline (HNMePh), N -methylbutylamine (HNMeBu), and N -methylcyclohexylamine (HNMeCy) were selected to vary electronic characteristics and steric bulk at the terminus. It is known that [Ta] gives the branched product exclusively with 1-octene . This trend continues with the VTPPs, as observed by the diagnostic doublet at about δ = 3.15–2.30 ppm in the 1 H NMR spectrum.…”

“…Unactivated alkyl amines are generally challenging substrates in HAA, and HNMeBu is particularly challenging due to the minimal steric bulk of this amine. HAA catalysis is known to require a degree of steric congestion to optimize catalytic turnover . For reactions with VT300 and VT3000 with HNMePh, the TOF is comparable to the 13 h –1 reported for 1-octene with HNMePh, showing that macromolecular substrates are readily accommodated by this catalyst .…”

“…HAA catalysis is known to require a degree of steric congestion to optimize catalytic turnover . For reactions with VT300 and VT3000 with HNMePh, the TOF is comparable to the 13 h –1 reported for 1-octene with HNMePh, showing that macromolecular substrates are readily accommodated by this catalyst . Although 5 mol % was used for in situ experiments, loadings as low as 1 and 2 mol % [Ta] could be used to aminate VT300 and VT3000 with HNMePh within 24 h at the 0.1 g scale.…”