Intramolecular Hydroamination Of Alkenes Research Articles

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination.

Kinetic studies on the intramolecular hydroamination of protected variants of 2,2-diphenylpent-4-en-1-amine were carried out under a variety of conditions with cationic gold catalysts supported by phosphine ligands. The impact of ligand on gold, protecting group on nitrogen, and solvent and additive on reaction rates was determined. The most effective reactions utilized more Lewis basic ureas, and more electron-withdrawing phosphines. A DCM/alcohol cooperative effect was quantified, and a continuum of isotope effects was measured with low KIE's in the absence of deuterated alcoholic solvent, increasing to large solvent KIE's when comparing reactions in pure MeOH to those in pure MeOH-d4. The effects are interpreted both within the context of a classic gold π-activation/protodeauration mechanism and a general acid-catalyzed mechanism without intermediate gold alkyls.

Silver Dependent Enantiodivergent Gold(I) Catalysed Asymmetric Intramolecular Hydroamination of Alkenes: A Theoretical Study

We report a theoretical study of the first silver-dependent enantiodivergent gold-catalysed reaction. The combination of a single chiral binuclear gold(I) chloride complex and silver perchlorate catalyses the asymmetric intramolecular hydroamination of alkenes and affords both enantiomers of the products by applying a simple solvent change from toluene to methanol. A gold-silver chloride adduct that occurs only in methanol appears to control the enantioinversion. If one gold atom coordinates and activates the alkene moiety, the other gold is included in an adduct with silver chloride, which coordinates a methanol solvent molecule and further interacts with the amine function. If the use of toluene implies free anions and affords (S)-enantiomer, methanol allows a proximal interaction with the amine, leads to an opposite stereodifferentiation of the two diastereomeric intermediates during the final protodeauration step and results in the (R)-enantiomer.

Intramolecular Alkene Hydroamination with Hybrid Catalysts Consisting of a Metal Salt and a Neutral Organic Base

Hybrid catalysts consisting of alkaline earth iodides (AeI2) and the Schwesinger base tBuP4 catalyse the intramolecular alkene hydroamination of H2C=CHCH2CR2CH2NH2 [CR2=CPh2, C(CH2)5, CMe2]. Activities decrease along the row: Ca > Sr >> Mg > Ba. Hybrid catalysts consisting of tBuP4 and ZnI2, AlI3, FeCI3 or NaI were found to be fully inactive. Also, the hybrid catalyst tBuP3/CaI2 was not active which means that the base strength of the non‐nucleophilic organic base must be higher than that of tBuP3 (pKa BH+ = 38.6). Combinations of tBuP4 with CaX2 (X = Cl, Br, OiPr, OTf, NTf2) were found to be fully inactive which may in part be explained by poor solubility. The hybrid catalysis method is therefore limited to the combination tBuP4/CaI2 but the iodide ligands may be partially or fully replaced by chiral ligands. Chiral modifications of the hybrid catalysts gave in intramolecular alkene hydroamination ee values up to 33 %.

Enantioselective Hydroamination of Alkenes with Sulfonamides Enabled by Proton-Coupled Electron Transfer.

An enantioselective, radical-based method for the intramolecular hydroamination of alkenes with sulfonamides is reported. These reactions are proposed to proceed via N-centered radicals formed by proton-coupled electron transfer (PCET) activation of sulfonamide N-H bonds. Noncovalent interactions between the neutral sulfonamidyl radical and a chiral phosphoric acid generated in the PCET event are hypothesized to serve as the basis for asymmetric induction in a subsequent C-N bond forming step, achieving selectivities of up to 98:2 er. These results offer further support for the ability of noncovalent interactions to enforce stereoselectivity in reactions of transient and highly reactive open-shell intermediates.

Bulky guanidinate calcium and zinc complexes as catalysts for the intramolecular hydroamination

Mixed guanidinato-amido supported complexes of calcium, LCaN(SiMe3)2∙2THF (1) [L = {ArNC(NiPr2)NAr} (Ar = 2,6-Me2-C6H3)] and zinc, LZnN(SiMe3)2 (2) & L1ZnN(SiMe3)2 (3) [L1 = {Ar'NC(NiPr2)NAr'} (Ar' = 2,6- iPr2-C6H3)] have been synthesized by salt metathesis method. Reaction between LH or L1H and two equivalents of KN(SiMe3)2 in THF and the resultant reaction mixture upon treatment with CaI2 or ZnCl2 led to the formation of heteroleptic calcium or zinc complexes. All three compounds (1–3) were characterized by multinuclear (1H, 13C, 29Si) magnetic resonance spectroscopy, elemental analysis and single crystal X-ray diffraction methods. Solid state structures confirm that all are monomeric species. Furthermore, we have shown the catalytic application of these complexes for intramolecular hydroamination of amino alkenes. Interestingly, compound 1 exhibits as an excellent pre-catalyst for intramolecular hydroamination of various primary amino alkenes in the absence of any additional activator (co-catalyst). However, both compounds 1 and 2 show very good catalytic activity of hydroamination of various secondary amines in the presence of co-catalyst.

Tetranuclear Strontium and Barium Siloxide/Amide Clusters in Metal‐Ligand Cooperative Catalysis

One‐pot reaction of 2,6‐iPr2‐aniline (DIPP‐NH2) with (Me2SiO)3 and Sr[N(SiMe3)2]2 (SrN′′2) gave a tetranuclear cluster consisting of four dianions [OSiMe2N‐DIPP]2– and four Sr2+ ions solvated each by one THF ligand. The general applicability of this method was investigated by variation of amine and metal. Anilines with smaller substituents led to insoluble uncharacterized coordination polymers, whereas bulkier anilines gave soluble product mixtures that could not be purified. Primary alkylamines neither led to isolable products. Introduction of a tBu group in para‐position of DIPP‐NH2, however, gave an isostructural cluster with increased solubility. Similar clusters could be obtained with barium. Both, the Sr and Ba clusters, were found to be active catalysts for a wide range of transformations: intramolecular alkene hydroamination, alkene hydrophoshination, pyridine hydroboration, pyridine hydrosilylation, and alkene hydrosilylation. The Ba catalysts were generally more active than the Sr catalysts. The tBu‐substituent in para‐position also had an accelerating effect, which is likely due to improved solubility.

Syntheses of Heteroleptic Amidinate Strontium Complexes Using a Superbulky Ligand

Strontium complexes are presented with two different bulky amidinate ligands (Am): tBuC(N-DIPP)2 (DIPP = 2,6-diisopropylphenyl), abbreviated here as tBuAmDIPP, and (p-tolyl)C(N-Ar‡)2 (Ar‡ = 2,6-Ph2CH-4-iPr-phenyl) abbreviated here as pTolAmAr‡. The amidine tBuAmDIPP-H was deprotonated by Sr[N(SiMe3)2]2 in benzene at 60 °C. Although the product, tBuAmDIPPSrN(SiMe3)2, could be characterized by NMR, attempts to isolate it led to ligand scrambling via a Schlenk equilibrium. Reaction of in situ prepared tBuAmDIPPSrN(SiMe3)2 with PhSiH3 gave PhH2SiN(SiMe3)2 and presumably the intermediate tBuAmDIPPSrH, but the latter is not stable and the homoleptic complex (tBuAmDIPP)2Sr was isolated and structurally characterized. Deprotonation of the bulkier amidine pTolAmAr‡-H with Sr[N(SiMe3)2]2 needed forcing conditions, inevitably giving rise to deprotonation of the Ph2CH substituent as well. Reaction of pTolAmAr‡-H with the less bulky and less basic Sr[N(SiHMe2)2]2, however, gave the heteroleptic product pTolAmAr‡SrN(SiHMe2)2, which has been structurally characterized. The latter was also at 60 °C stable toward ligand scrambling. Reaction with PhSiH3 did give hydride exchange, but the product pTolAmAr‡SrH decomposed even at −30 °C. Instead, an amidinate complex with a deprotonated Ph2CH substituent was isolated and structurally characterized (7). The latter catalyzed the intramolecular alkene hydroamination.

Intramolecular alkene hydroamination and degradation of amidines: divergent behavior of rare earth metal amidinate intermediates

The methods for catalytic intramolecular alkene hydroamination and degradation of amidines have been established. Furthermore, a tandem reconstruction/cyclization of amidines has also been developed.

Visible light-driven photocatalytic generation of sulfonamidyl radicals for alkene hydroamination of unsaturated sulfonamides.

A visible light-driven photocatalytic generation of sulfonamidyl radicals, and application to intramolecular alkene hydroamination, has been accomplished, providing a mild and efficient approach to various functionalized isoxazolidines. The success of this protocol is based on the strategy of oxidative deprotonation electron transfer by merging the base and the photocatalyst under visible light irradiation, obviating installation of a photolabile handle or stoichiometric external oxidants.

Intramolecular Hydroamination by a Primary Amine of an Unactivated Alkene on Gold Nanoclusters: A DFT Study

AbstractDensity functional theory calculations have been used to investigate the mechanism of intramolecular hydroamination of unactivated alkenes by using primary amines on gold nanoclusters (NCs) under aerobic conditions. By examining the activation modes in the cyclization process, the olefin activation mechanism was calculated to be the most energetically feasible of the three possible pathways. The amine activation pathway suffered from a high activation barrier, which means that this pathway is unlikely to take place on gold NCs. The catalytic cycle comprises five elementary steps: (1) adsorption of O2 on Au NCs results in superoxo‐like species and provides Lewis acidic sites that allow the nucleophilic substrate, 2,2‐diphenyl‐4‐penten‐1‐amine, to be adsorbed effectively; (2) intramolecular cyclization (C−N bond formation) takes place on the Au NCs through anti‐addition of the amino group; (3) hydroperoxy moiety formation by hydrogen transfer from the cyclic intermediate to superoxo‐like species; (4) the formation of hydrogen peroxide and (5) product involves hydrogen transfer from a hydrated formic acid. Natural bond orbital analysis of the transition states that arise during C−N bond formation reveals that anti‐addition of the substrate is preferred over the syn‐addition mechanism. A possible side reaction, the formation of 2‐methylene‐4,4‐diphenylpyrrolidine through β‐hydrogen elimination, is also discussed.

Gold(I)-Catalysed Asymmetric Hydroamination of Alkenes: A Silver- and Solvent-Dependent Enantiodivergent Reaction.

In the present study, we report the first silver-dependent enantiodivergent gold-catalysed reaction. The asymmetric intramolecular hydroamination of alkenes catalysed by the combination of a single chiral binuclear gold(I) chloride complex and silver perchlorate can afford both enantiomers of the products by a simple solvent change from toluene to methanol. Such an enantiodivergent reaction is strictly independent of the reaction temperature or of the nature of the catalyst anion and displays the same first-order kinetic rate law with respect to substrate concentration in both solvents. Beyond a simple solvent effect the enantioinversion is controlled by gold-silver chloride adducts which occur only in methanol and allow a dual activation of the reagent. While one single gold atom activates the alkene moiety, the other gold atom forms an oxophilic gold-silver chloride adduct which is likely to interact with the carbamate function. By comparison with toluene, which affords (S)-enantiomer, this proximal and bimetallic activation would allow an opposite stereodifferentiation of the two diastereomeric intermediates during the final protodeauration step and lead therefore to the (R)-enantiomer.

Gold(I)-Catalyzed Intramolecular Hydroamination of Unactivated Terminal and Internal Alkenes with 2-Pyridones.

The cationic gold phosphine complex [(P1)Au(NCMe)]+SbF6- [P1 = P(t-Bu)2o-biphenyl; 2] catalyzes the intramolecular hydroamination of 6-alkenyl-2-pyridones to form 1,6-carboannulated 2-pyridones in high yield. The hydroamination of 6-(γ-alkenyl)-2-pyridones was effective for monosubstituted and 1,1- and 1,2-disubstituted aliphatic alkenes, and the method was likewise effective for the hydroamination of 6-(δ-alkenyl)-2-pyridones. Spectroscopic analysis of mixtures of 6-(3-butenyl)-2-pyridone, (P1)AuCl, and AgSbF6 established the N-bound 2-hydroxypyridine complex [(P1)Au(NC6H3-2-OH-6-CH2CH2CH═CH2)]+ SbF6- as the catalyst resting state.

Bora-amidinate as a cooperative ligand in group 2 metal catalysis.

Syntheses and crystal structures of the monomeric bora-amidinate (bam) complexes DIPPNBN-Mg·(THF)3 and DIPPNBN-Ca·(THF)4 are presented; DIPPNBN = HB[N(2,6-iPr2-C6H3)]2. The simplicity of their 1H NMR spectra in THF-d8 suggest that their monomeric solid state structures are retained in solution. DIPPNBN-Mg·(THF)3 in C6D6, however, is in equilibrium with a dimeric species. Calculations (B3PW91/6-311++G**) reveal a very high localized negative charge (NPA: -1.103) on the N atoms in DIPPNBN-Mg. The strongly basic properties of the bam ligand are in agreement with catalytic activity of these complexes in the intramolecular alkene hydroamination. A mechanism is proposed in which the bam ligand is non-innocent and cooperative, playing an active role in substrate deprotonation and product protonation.

Brønsted acid-catalysed intramolecular hydroamination of unactivated alkenes: metal triflates as an in situ source of triflic acid

Hydroamination of alkenes or alkynes is one of the most straightforward methods to form C-N bonds and nitrogen-containing heterocycles. A simple Lewis acid Al(OTf)3 was found to be an effective precatalyst for the hydroamination of unactivated primary and secondary alkenylamines between 110 and 150 °C. Subsequent studies show that other metal triflates are also effective precatalysts for the hydroamination reactions. For metal triflate salts, mechanistic studies, including kinetics, are consistent with the in situ generation of triflic acid, which likely serves as the active catalyst.

A New N‐Trityl‐Substituted Aminopyridinato Titanium Catalyst for Hydroamination and Hydroaminoalkylation Reactions – Unexpected Intramolecular C–H Bond Activation

AbstractSterically demanding 2,6‐bis(tritylamino)pyridine is used for the synthesis of a mono(2,6‐diaminopyridinato) titanium complex that undergoes unexpected intramolecular C–H bond activation to give access to an unusual 1‐titanaisoindoline derivative. Both titanium complexes do not show high catalytic activity for hydroaminoalkylation reactions of alkenes but exceptional results are obtained in the field of alkene, alkyne, and allene hydroamination including room temperature activity for intramolecular alkene hydroamination, excellent regioselectivity of intermolecular alkyne and allene hydroamination as well as selectivity for hydroamination over hydroaminoalkylation during cyclization reactions of primary aminoalkenes.

Brønsted Acid Catalyzed Asymmetric Hydroamination of Alkenes: Synthesis of Pyrrolidines Bearing a Tetrasubstituted Carbon Stereocenter

AbstractThe first highly enantioselective Brønsted acid catalyzed intramolecular hydroamination of alkenes enables the efficient construction of a series of chiral (spirocyclic) pyrrolidines with an α‐tetrasubstituted carbon stereocenter with excellent functional group tolerance. A unique feature of this strategy is the use of a thiourea group acting as both the activating and the directing group through cooperative multiple hydrogen bonding with a Brønsted acid and the double bond. The utility of this method is highlighted by the facile construction of chiral synthetic intermediates and important structural motifs that are widely found in organic synthesis.

Brønsted Acid Catalyzed Asymmetric Hydroamination of Alkenes: Synthesis of Pyrrolidines Bearing a Tetrasubstituted Carbon Stereocenter.

The first highly enantioselective Brønsted acid catalyzed intramolecular hydroamination of alkenes enables the efficient construction of a series of chiral (spirocyclic) pyrrolidines with an α-tetrasubstituted carbon stereocenter with excellent functional group tolerance. A unique feature of this strategy is the use of a thiourea group acting as both the activating and the directing group through cooperative multiple hydrogen bonding with a Brønsted acid and the double bond. The utility of this method is highlighted by the facile construction of chiral synthetic intermediates and important structural motifs that are widely found in organic synthesis.

Early main group metal catalysis: how important is the metal?

Organocalcium compounds have been reported as efficient catalysts for various alkene transformations. In contrast to transition metal catalysis, the alkenes are not activated by metal-alkene orbital interactions. Instead it is proposed that alkene activation proceeds through an electrostatic interaction with a Lewis acidic Ca(2+) . The role of the metal was evaluated by a study using the metal-free catalysts: [Ph2 N(-) ][Me4 N(+) ] and [Ph3 C(-) ][Me4 N(+) ]. These "naked" amides and carbanions can act as catalysts in the conversion of activated double bonds (CO and CN) in the hydroamination of ArNCO and RNCNR (R=alkyl) by Ph2 NH. For the intramolecular hydroamination of unactivated CC bonds in H2 CCHCH2 CPh2 CH2 NH2 the presence of a metal cation is crucial. A new type of hybrid catalyst consisting of a strong organic Schwesinger base and a simple metal salt can act as catalyst for the intramolecular alkene hydroamination. The influence of the cation in catalysis is further evaluated by a DFT study.

Early Main Group Metal Catalysis: How Important is the Metal?

AbstractOrganocalcium compounds have been reported as efficient catalysts for various alkene transformations. In contrast to transition metal catalysis, the alkenes are not activated by metal–alkene orbital interactions. Instead it is proposed that alkene activation proceeds through an electrostatic interaction with a Lewis acidic Ca2+. The role of the metal was evaluated by a study using the metal‐free catalysts: [Ph2N−][Me4N+] and [Ph3C−][Me4N+]. These “naked” amides and carbanions can act as catalysts in the conversion of activated double bonds (CO and CN) in the hydroamination of ArNCO and RNCNR (R=alkyl) by Ph2NH. For the intramolecular hydroamination of unactivated CC bonds in H2CCHCH2CPh2CH2NH2 the presence of a metal cation is crucial. A new type of hybrid catalyst consisting of a strong organic Schwesinger base and a simple metal salt can act as catalyst for the intramolecular alkene hydroamination. The influence of the cation in catalysis is further evaluated by a DFT study.

Enantioselective Intramolecular Hydroamination of Unactivated Alkenes Catalyzed by Mono‐ and Bis(gold) Phosphine Complexes

AbstractA 1:2 mixture of (P1)(AuCl)2 [P1=(S)‐DTBM‐MeO‐BIPHEP] and silver tetrafluoroborate (AgBF4) in methanol catalyzes the intramolecular hydroamination of unactivated alkenes with carbamates and ureas to form pyrrolidine derivatives with up to 85% ee.magnified image