In Situ Generation of a Regio- and Diastereoselective Hydroaminoalkylation Catalyst Using Commercially Available Starting Materials

Abstract

The design of an easy to use catalyst system for the regio- and diastereoselective intermolecular hydroaminoalkylation of alkenes with secondary amines is reported. The method utilizes commercially available ligands and tantalum starting materials, and does not require the isolation of air and water sensitive organometallic complexes. The in situ prepared catalyst is active toward a variety of secondary amine substrates, including those with ethyl substituents which yield α- and β-alkylated amines as a single diastereomer. This catalytic transformation can be used to prepare amines containing functionality that promotes ring closure to achieve the diastereoselective synthesis of di- and trialkylated N-heterocycles.

Zirconium Catalyzed Hydroaminoalkylation for the Synthesis of α‐Arylated Amines and N‐Heterocycles

“…This work shows that steric parameters also play a role with this zirconium catalyst. Literature reports on tantalum [24] and titanium [13] HAA with vinylsilane show the formation of mixture of regioisomers or exclusive formation of the linear product, respectively. To date, steric effects dominate over electronic parameters in zirconium catalyzed reactivity.…”

“…[16,23] This work shows that steric parameters also play ar ole with this zirconium catalyst. Literature reports on tantalum [24] and titanium [13] HAA with vinylsilane show the formation of mixture of regioisomers or exclusive formation of the linear product, respectively.T od ate, steric effectsd ominate over electronic parameters in zirconium catalyzed reactivity. The five-membered ring intermediates J and K undergo protonolysis to afford complexes L or M,r espectively.T he final CÀH activation event happens via hydrogen abstraction,l eadingt o the reformation of zirconaaziridine I with concomitantl iberation of the desired a-(hetero)arylated amines.…”

Hydroamination and Hydroaminoalkylation of Alkenes by Group 3–5 Elements: Recent Developments and Comparison with Late Transition Metals

“…Comparative kinetic investigations with these systems led to the identification of numerous and intricate off-cycle equilibria, drastically linked to the ligand environments and specifically to the presence of dimethylamido goups. The practicality of this procedure could be demonstrated by the easy in situ preparation of the active precatalysts from commercially available stable precursors to synthesize branched alkylamines regio- and diastereoselectively . A more recent example, from this year, proposed again a facile in situ synthesis of very active tantalum precatalysts ( 15 , Scheme ) from ureate salts and the more thermally stable Ta­(CH 2 SiMe 3 ) 3 Cl 2 complex .…”

“…The practicality of this procedure could be demonstrated by the easy in situ preparation of the active precatalysts from commercially available stable precursors to synthesize branched alkylamines regio-and diastereoselectively. 48 A more recent example, from this year, proposed again a facile in situ synthesis of very active tantalum precatalysts (15, Scheme 11) from ureate salts and the more thermally stable Ta(CH 2 SiMe 3 ) 3 Cl 2 complex. 49 These complexes allowed the reaction between N-methylaniline derivatives and terminal olefins to be almost complete in 2 h and in 5 h when cyclic internal alkenes are concerned.…”

Hydrogen-bonding chain and dimer motifs in pyridinium and morpholinium hydrogen oxalate salts

“…In compound 3, the hydrogen oxalate is the trans conformer and produces a chain along the a-axis direction and is comparable to compounds reported in the Cambridge Structural Database (CSD version 5.39, updated August 2018, Groom et al, 2016, such as ACOQER (Mora et al, 2017) and FOMBIU (Traut-Johnstone et al, 2014). The hydrogen oxalates in compound 2 are in the cis conformation and form a hydrogen-bonded pair, as seen in a small handful of structures: the combination of this pair-wise interaction with a birfurcated hydrogen bond to a pyridinium cation is also seen in EZECOC (Androš et al, 2011;Chen et al 2012,), GULQOV (Thomas et al, 2015;Suresh et al, 2015), LOFMAW (Hu et al, 2014), YEPBAX (Said et al, 2006), YINVUO (Martin et al, 2013) and XEJRIQ (Edwards & Schafer, 2017). The chain type in 1 is not seen in any hydrogen oxalate compounds in the CSD.…”