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 .     

Lanthanide complexes coordinated by N-substituted (R)-1,1'-binaphthyl-2,2'-diamido ligands in the catalysis of enantioselective intramolecular hydroamination

A new family of lanthanide ionic complexes derived from chiral, substituted (R)-binaphthylamine ligands, [Li(thf)(4)][Ln{(R)-C(20)H(12)(NR)(2)}(2)] (Ln=Yb, Sm, Nd, or Lu), has been synthesized and characterized by X-ray crystal structure analyses. All complexes have been tested as new catalysts for the hydroamination/cyclization of 1-(aminomethyl)-1-allylcyclohexane. Ytterbium complexes proved to be both the most active and the most enantioselective, and the use of the complex [Li(thf)(4)][Yb{(R)-C(20)H(12)(NC(3)H(7))(2)}(2)], bearing isopropyl radicals on the nitrogen atoms, allowed the formation of the corresponding spiropyrrolidine in high yield with up to 70 % ee.     

An easy-to-use, regioselective, and robust bis(amidate) titanium hydroamination precatalyst: mechanistic and synthetic investigations toward the preparation of tetrahydroisoquinolines and benzoquinolizine alkaloids

Amidate-supported titanium amido complexes are efficient and regioselective precatalysts for intermolecular hydroamination of terminal alkynes with primary amines. The synthesis and characterization of the first bis(amidate)-supported titanium-imido complex is reported. Its role as the active catalytic species is suggested in the course of product distribution studies using deuterated substrates. The bis(amidate)-supported precatalysts exhibit good functional-group tolerance, even performing hydroaminations in the presence of ester and amide groups. This functional-group tolerance was exploited in the synthesis of a variety of 1-substituted tetrahydroisoquinoline alkaloids and a one-pot hydroaminative procedure for the high yielding preparation of the benzo[a]quinolizine skeleton.     

Synthesis and characterization of new biphenolate and binaphtholate rare-Earth-metal amido complexes: catalysts for asymmetric olefin hydroamination/cyclization

Monomeric diolate amido yttrium complexes [Y[diolate][N(SiHMe(2))(2)](thf)(2)] can be prepared in good yield by treating [Y[N(SiHMe(2))(2)](3)(thf)(2)] with either 3,3'-di-tert-butyl-5,5',6,6'-tetramethyl-1,1'-biphenyl-2,2'-diol (H(2)(Biphen)), 3,3'-bis(2,4,6-triisopropylphenyl)-2,2'-dihydroxy-1,1'-dinaphthyl (H(2)(Trip(2)BINO)) or 3,3'-bis(2,6-diisopropylphenyl)-2,2'-dihydroxy-1,1'-dinaphthyl (H(2)(Dip(2)BINO)) in racemic and enantiopure form. The racemic complex [Y(biphen)[N(SiHMe(2))(2)](thf)(2)] dimerizes upon heating to give the heterochiral complex (R,S)-[Y(biphen)[N(SiHMe(2))(2)](thf)](2). The corresponding dimeric heterochiral lanthanum complex was the sole product in the reaction of H(2)(Biphen) with [La[N(SiHMe(2))(2)](3)(thf)(2)]. Single-crystal X-ray diffraction of both dimeric complexes revealed that the two Ln(biphen)[N(SiHMe(2))(2)](thf) fragments are connected through bridging phenolate groups of the biphenolate ligands. The two different phenolate groups undergo an intramolecular exchange process in solution leading to their equivalence on the NMR timescale. All complexes were active catalysts for the hydroamination/cyclization of aminoalkynes and aminoalkenes at elevated temperature, with [Y((R)-dip(2)bino)[N(SiHMe(2))(2)](thf)(2)] being the most active one giving enantioselectivities of up to 57 % ee. Kinetic resolution of 2-aminohex-5-ene proceeded with this catalyst with 6.4:1 trans selectivity to give 2,5-dimethylpyrrolidine with a k(rel) of 2.6.     

Catalytic Intramolecular Aminofluorination,Oxyfluorination, and Carbofluorination with a Stable and Versatile Hypervalent Fluoroiodine Reagent

Application of a fluoroiodine analogue of the Togni reagent was studied in fluorocyclization reactions. In the presence of a transition‐metal catalyst the applied fluoroiodine reagent can be used for aminofluorination, oxyfluorination, and carbofluorination reactions. The described procedure has a very broad synthetic scope for preparation of functionalized hetero‐ and isocyclic compounds having a tertiary fluorine substituent.     

Mechanism and exo-regioselectivity of organolanthanide-mediated intramolecular hydroamination/cyclization of 1,3-disubstituted aminoallenes: a computational study

The complete catalytic reaction course for the organolanthanide-assisted intramolecular hydroamination/cyclization (IHC) of 4,5-heptadien-1-ylamine by a prototypical [(eta(5)-Me5C5)2LuCH(SiMe3)2] precatalyst has been critically scrutinized by employing a reliable DFT method. A computationally verified mechanistic scenario for the IHC of 1,3-disubstituted aminoallene substrates has been proposed that is consistent with the empirical rate law determined by experiment and accounts for crucial experimental observations. It involves kinetically rapid substrate association and dissociation equilibria, facile and reversible intramolecular allenic C=C insertion into the Ln-N bond, and turnover-limiting protonation of the azacycle's tether functionality, with the amine-amidoallene-Ln adduct complex representing the catalyst's resting state. This mechanistic scenario bears resemblance to the mechanism that has been recently proposed in a computational exploration of aminodiene IHC. The unique features of the IHC of the two substrate classes are discussed. Furthermore, the thermodynamic and kinetic factors that control the regio- and stereoselectivity of aminoallene IHC have been elucidated. These achievements have provided a deeper insight into the catalytic structure-reactivity relationships in organolanthanide-assisted cyclohydroamination of unsaturated C-C functionalities.     

Bis(phosphinimino)methanide rare earth amides: synthesis, structure, and catalysis of hydroamination/cyclization, hydrosilylation, and sequential hydroamination/hydrosilylation

A series of yttrium and lanthanide amido complexes [Ln{N(SiHMe(2))2}2{CH(PPh(2)NSiMe(3))2}] (Ln=Y, La, Sm, Ho, Lu) were synthesized by three different pathways. The title compounds can be obtained either from [Ln{N(SiHMe(2))2}3(thf)2] and [CH(2)(PPh(2)NSiMe(3))2] or from KN(SiHMe(2))2 and [Ln{CH(PPh(2)NSiMe(3))2}Cl(2)]2, while in a third approach the lanthanum compound was synthesized in a one-pot reaction starting from K{CH(PPh(2)NSiMe(3))2}, LaCl3, and KN(SiHMe(2))2. All the complexes have been characterized by single-crystal X-ray diffraction. The new complexes, [Ln{N(SiHMe(2))2}2{CH(PPh(2)NSiMe(3))2}], were used as catalysts for hydroamination/cyclization and hydrosilylation reactions. A clear dependence of the reaction rate on the ionic radius of the center metal was observed, showing the lanthanum compound to be the most active one in both reactions. Furthermore, a combination of both reactions--a sequential hydroamination/hydrosilylation reaction--was also investigated.     

Selective synthesis of tricyclopentadiene from dicyclopentadiene with homogeneous Pd catalysts

We explored a simple synthetic strategy with homogeneous palladium catalysts to afford a [2 + 2] isomer of tricyclopentadiene in good yield (up to 98% from cyclopentadiene and up to 78% from dicyclopentadiene) with high selectivity. The effects of a variety of palladium precursors, phosphorus ligands and acids were investigated to improve the productivity and selectivity of the tricyclopentadiene synthesis. The reaction conditions were evaluated and their effects on the product distribution were also discussed. Copyright © 2014 John Wiley & Sons, Ltd.     

Metal‐Free Intramolecular Carbocyanation of Alkenes: Catalytic Stereoselective Construction of Pyrrolo[2,1‐a]isoquinolines with Multiple Substituents

The first catalytic stereoselective approach to prepare multiple substituted cyclic nitriles by means of a novel metal‐free intramolecular carbocyanation strategy has been developed, which provided an efficient protocol to construct densely functionalized diastereoenriched pyrrolo[2,1‐a]isoquinoline derivates under mild reaction conditions (up to 20/1 d.r., 98 % yield).     

Experimental and Theoretical Study of an Intramolecular CF3‐Group Shift in the Reactions of α‐Bromoenones with 1,2‐Diamines

The reactions of trifluoromethylated 2‐bromoenones and N,N′‐dialkyl‐1,2‐diamines have been studied. Depending on the structures of the starting compounds, the formation of 2‐trifluoroacetylpiperazine or 3‐trifluoromethylpiperazine‐2‐ones was observed. The mechanism of the reaction is discussed in terms of multistep processes involving sequential substitution of bromine in the starting α‐bromoenones and intramolecular cyclization of the captodative aminoenones as key intermediates to form the target heterocycles. The results of theoretical calculations are in perfect agreement with the experimental data. The unique role of the trifluoromethyl group in this reaction is demonstrated.     

Enantioselective Construction of Vicinal Tetrasubstituted Stereocenters by the Mannich Reaction of Silyl Ketene Imines with Isatin‐Derived Ketimines

A highly enantioselective Mannich reaction of silyl ketene imines with isatin‐derived ketimines has been realized by using a chiral N,N′‐dioxide/Zn^II catalyst. A variety of β‐amino nitriles containing congested vicinal tetrasubstituted stereocenters were obtained with excellent outcomes (up to 98 % yield, >19:1 d.r. and 99 % ee). Based on the experimental investigations, a possible transition state has been proposed to explain the origin of the asymmetric induction.