Comparison of yttrium binaphthylamido alkyl and amide complexes for enantioselective intramolecular hydroamination

A chiral trisamido yttrium complex Y[(R)-C₂₀H₁₂(NC₅H₉)₂][NiPr₂][THF]₂·LiCl coordinated by N-cyclopentyl binaphthylamine ligand has been prepared in situ and characterised by NMR spectroscopy. It has been revealed as an efficient catalyst for intramolecular hydroamination of aminoolefins. Comparison with neutral alkyl, ate alkyl or ate tetraamido complexes coordinated by the same ligand indicated that this complex was the most efficient catalyst of the series for its both activity and enantioselectivity values.     

Phenalenyl‐Based Organozinc Catalysts for Intramolecular Hydroamination Reactions: A Combined Catalytic,Kinetic, and Mechanistic Investigation of the Catalytic Cycle

Herein, we report the synthesis and characterization of two organozinc complexes that contain symmetrical phenalenyl (PLY)‐based N,N‐ligands. The reactions of phenalenyl‐based ligands with ZnMe₂ led to the formation of organozinc complexes [N(Me),N(Me)‐PLY]ZnMe ( 1 ) and [N(iPr),N(iPr)‐PLY]ZnMe ( 2 ) under the evolution of methane. Both complexes ( 1 and 2 ) were characterized by NMR spectroscopy and elemental analysis. The solid‐state structures of complexes 1 and 2 were determined by single‐crystal X‐ray crystallography. Complexes 1 and 2 were used as catalysts for the intramolecular hydroamination of unactivated primary and secondary aminoalkenes. A combined approach of NMR spectroscopy and DFT calculations was utilized to obtain better insight into the mechanistic features of the zinc‐catalyzed hydroamination reactions. The progress of the catalysis for primary and secondary aminoalkene substrates with catalyst 2 was investigated by detailed kinetic studies, including kinetic isotope effect measurements. These results suggested pseudo‐first‐order kinetics for both primary and secondary aminoalkene activation processes. Eyring and Arrhenius analyses for the cyclization of a model secondary aminoalkene substrate afforded ΔH^≠=11.3 kcal mol^?1, ΔS^≠=?35.75 cal K^?1 mol^?1, and E_a=11.68 kcal mol^?1. Complex 2 exhibited much‐higher catalytic activity than complex 1 under identical reaction conditions. The in situ NMR experiments supported the formation of a catalytically active zinc cation and the DFT calculations showed that more active catalyst 2 generated a more stable cation. The stability of the catalytically active zinc cation was further supported by an in situ recycling procedure, thereby confirming the retention of catalytic activity of compound 2 for successive catalytic cycles. The DFT calculations showed that the preferred pathway for the zinc‐catalyzed hydroamination reactions is alkene activation rather than the alternative amine‐activation pathway. A detailed investigation with DFT methods emphasized that the remarkably higher catalytic efficiency of catalyst 2 originated from its superior stability and the facile formation of its cation compared to that derived from catalyst 1 .     

Metal–Ligand Cooperation in Catalytic Intramolecular Hydroamination: A Computational Study of Iridium–Pyrazolato Cooperative Activation of Aminoalkenes

The present study comprehensively explores diverse mechanistic pathways for intramolecular hydroamination of prototype 2,2‐dimethyl‐4‐penten‐1‐amine by Cp*Ir chloropyrazole ( 1 ; Cp*=pentamethylcyclopentadienyl) in the presence of KOtBu base with the aid of density functional theory (DFT) calculations. The most accessible mechanistic pathway for catalytic turnover commences from Cp*Ir pyrazolato (Pz) substrate adduct 2 ?S, representing the catalytically competent compound and proceeds via initial electrophilic activation of the olefin C?C bond by the metal centre. It entails 1) facile and reversible anti nucleophilic amine attack on the iridium–olefin linkage; 2) Ir? C bond protonolysis via stepwise transfer of the ammonium N? H proton at the zwitterionic [Cp*IrPz–alkyl] intermediate onto the metal that is linked to turnover‐limiting, reductive, cycloamine elimination commencing from a high‐energy, metastable [Cp*IrPz–hydrido–alkyl] species; and 3) subsequent facile cycloamine liberation to regenerate the active catalyst species. The amine–iridium bound 2 a ?S likely corresponds to the catalyst resting state and the catalytic reaction is expected to proceed with a significant primary kinetic isotope. This study unveils the vital role of a supportive hydrogen‐bonded network involving suitably aligned β‐basic pyrazolato and cycloamido moieties together with an external amine molecule in facilitating metal protonation and reductive elimination. Cooperative hydrogen bonding thus appears pivotal for effective catalysis. The mechanistic scenario is consonant with catalyst performance data and furthermore accounts for the variation in performance for [Cp*IrPz] compounds featuring a β‐ or γ‐basic pyrazolato unit. As far as the route that involves amine N? H bond activation is concerned, a thus far undocumented pathway for concerted amidoalkene → cycloamine conversion through olefin protonation by the pyrazole N? H concurrent with N? C ring closure is disclosed as a favourable scenario. Although not practicable in the present system, this pathway describes a novel mechanistic variant in late transition metal–ligand bifunctional hydroamination catalysis that can perhaps be viable for tailored catalyst designs. The insights revealed herein concerning the operative mechanism and the structure–reactivity relationships will likely govern the rational design of late transition metal–ligand bifunctional catalysts and facilitate further conceptual advances in the area.     

Addition–Hydroamination Reactions of Propargyl Cyanamides: Rapid Access to Highly Substituted 2‐Aminoimidazoles

A valuable pharmacophore , the 2‐aminoimidazole moiety, can be accessed with a variety of substitution patterns through an addition–hydroamination–isomerization sequence (see scheme; R¹,R⁴,R⁵=alkyl; R³=alkyl, aryl; R²=H, alkyl, aryl). The synthesis of the propargyl cyanamide precursors through a three‐component coupling enables the preparation of this important heterocyclic core structure in just three steps.

     

A chiral phenoxyamine magnesium catalyst for the enantioselective hydroamination/cyclization of aminoalkenes and intermolecular hydroamination of vinyl arenes

If Grignard had only known! A chiral magnesium complex catalyzes the intramolecular hydroamination/cyclization of aminoalkenes with high efficiency at temperatures as low as ?20?°C and enantioselectivities as high as 93?%?ee. The high activity of this system also allows the catalytic intermolecular anti-Markovnikov addition of pyrrolidine and benzylamine to vinyl arenes.     

Copper(I)-catalyzed synthesis of 1-arylpyrazolo[5,1-b]quinazolin-9(1H)-one via intramolecular alkyne hydroamination

The 1-arylpyrazolo[5,1-b]quinazolin-9(1H)-one derivatives were obtained via intramolecular alkyne hydroamination reaction of 2-amino-N′-arylbenzohydrazide and alkynal diethyl acetal in the presence of CuBr and Cs₂CO₃. This new procedure provides an efficient method to construct fused tricyclic heterocycle containing both pyrazole and quinazoline analogues.     

Metal‐to‐Ligand Alkyl Migration Inducing Carbon–Sulfur Bond Cleavage in Dialkyl Yttrium Complexes Supported by Thiazole‐Containing Amidopyridinate Ligands: Synthesis,Characterization, and Catalytic Activity in the Intramolecular Hydroamination Reaction

Neutral Y^III dialkyl complexes supported by tridentate N^?,N,N monoanionic methylthiazole– or benzothiazole–amidopyridinate ligands have been prepared and completely characterized. Studies on their stability in solution revealed progressive rearrangement of the coordination sphere in the benzothiazole‐containing system through an unprecedented metal‐to‐ligand alkyl migration and subsequent thiazole ring opening. Attempts to synthesize hydrido species from the dialkyl precursor led to the generation of a dimeric yttrium species stabilized by a trianionic N^?,N,N^?,S^? ligand as the result of metal‐to‐ligand hydride migration with chemoselective thiazole ring opening and subsequent dimerization through intermolecular addition of the residual Y?H group to the imino fragment of a second equivalent of the ring‐opened intermediate. DFT calculations were used to elucidate the thermodynamics and kinetics of the process, in support of the experimental evidence. Finally, all isolated yttrium complexes, especially their cationic forms prepared by activation with the Lewis acid Ph₃C⁺[B(C₆F₅)₄]^?, were found to be good candidate catalysts for intramolecular hydroamination/cyclization reactions. Their catalytic performance with a number of primary and secondary amino alkenes was assessed.     

Well‐Defined Four‐Coordinate Iron(II) Complexes For Intramolecular Hydroamination of Primary Aliphatic Alkenylamines

Despite the growing interest in iron catalysis and hydroamination reactions, iron‐catalyzed hydroamination of unprotected primary aliphatic amines and unactivated alkenes has not been reported to date. Herein, a novel well‐defined four‐coordinate β‐diketiminatoiron(II) alkyl complex is shown to be an excellent precatalyst for the highly selective cyclohydroamination of primary aliphatic alkenylamines at mild temperatures (70–90 °C). Both empirical kinetic analyses and the reactivity of an isolated iron(II) amidoalkene dimer, [LFe(NHCH₂CPh₂CH₂CH?CH₂)]₂ favor a stepwise σ‐insertive mechanism that entails migratory insertion of the pendant alkene into an iron–amido bond associated with a rate‐determining aminolysis step.