Rhodium-catalyzed anti-Markovnikov hydroamination of vinylarenes

The transition metal-catalyzed anti-Markovnikov hydroamination of unactivated vinylarenes with a rhodium complex of DPEphos is reported. The reaction of electron-neutral or electron-rich vinylarenes with a variety of secondary amines in the presence of catalyst forms the products from anti-Markovnikov hydroamination in high yields. Reactions of morpholine, N-phenylpiperazine, N-Boc-piperazine, piperidine, 2,5-dimethylmorpholine, and perhydroisoquinoline reacted with styrene to form the amine product in 51-71% yield. Reactions of a variety of vinylarenes with morpholine generated amine as the major product. Reactions of morpholine with electron-poor vinylarenes gave lower amine:enamine ratios than reactions of electron-rich vinylarenes at the same concentration of vinylarene, but conditions were developed with lower concentrations of electron-poor vinylarene to maintain formation of the amine as the major product. Reactions of dimethylamine with vinylarenes were fast and formed amine as the major product. Mechanistic studies on the hydroamination process showed that the amine:enamine ratio was lower for reactions conducted with higher concentrations of vinylarene and that one vinylarene influences the selectivity for reaction of another. A mechanism proceeding through a metallacyclic intermediate that opens in the presence of a second vinylarene accounts for these and other mechanistic observations.     

Mechanistic Studies of Ruthenium-Catalyzed Anti-Markovnikov Hydroamination of Vinylarenes: Intermediates and Evidence for Catalysis through pi-Arene Complexes

Studies are described that reveal the steps of the anti-Markovnikov hydroamination of vinylarenes with alkylamines catalyzed by Ru(COD)(2-methylallyl)2, bis(diphenylphosphino)pentane, and TfOH. Treatment of the catalyst components with an excess of styrene under the catalytic reaction conditions afforded a new ruthenium eta6-styrene complex with an ancillary tridentate PCP ligand. This ruthenium complex was active as catalyst for the hydroamination of styrene with morpholine to give the anti-Markovnikov adduct as a single regioisomer in high yield. Studies of the reactivity of the eta6-styrene complex revealed two reactions that comprise a catalytic cycle for anti-Markovnikov hydroamination: nucleophilic addition of morpholine to the ruthenium eta6-styrene complex to afford a ruthenium eta6-(2-aminoethyl)benzene complex and arene exchange of the ruthenium eta6-(2-aminoethyl)benzene complex with styrene to regenerate the ruthenium eta6-styrene complex. The addition of morpholine and the exchange of arene occurred with comparable rates. These results strongly suggest that the ruthenium-catalyzed anti-Markovnikov addition of alkylamines to vinylarenes occurs by a new reaction mechanism for hydroamination involving nucleophilic attack on the eta6-vinylarene complex and exchange of the aminoalkylarene complex product with free vinylarene. This mechanism is a rare example of catalytic chemistry through pi-arene complexes. These mechanistic data were used to select derivatives of the DPPP ligand that improve the rates of the catalytic process.     

Intermolecular, markovnikov hydroamination of vinylarenes with alkylamines

A transition metal-catalyzed intermolecular hydroamination of vinylarenes with alkylamines is reported. The combination of Pd(O2CCF3)4, DPPF, and TfOH was the most effective catalyst of those tested. Control experiments without palladium, acid, or ligand all occurred in low yield. The reaction of various vinylarenes with cyclic and acyclic alkylamines in the presence of 5 mol % of this catalyst formed the corresponding arylethylamine products in moderate to high yields. For example, reactions of morpholine, 4-phenylpiperazine, 4-Boc-piperazine, isoindoline, and tetrahydroisoquinoline with styrene all occurred in 58-75% yield. Acyclic amines such as N-benzylmethylamine and n-hexylmethylamine reacted with 2-vinylnaphthalene in 63% and 53% yields, respectively. Mechanistic investigations showed that the reaction occurred through an eta3-arylethyl palladium complex. The reactions of this complex with alkylamines generated product in combination with regenerating free vinylarene, Pd(0), and ammonium salt. Thus, one hurdle to developing hydroamination of vinylarenes with palladium complexes is the faster elimination of free vinylarene from the eta3-arylethyl complex than addition to form the C-N bond. The feasibility of conducting enantioselective hydroaminations with alkylamines was also examined. The product from addition of N-benzylmethylamine to 2-vinylnaphthalene was generated in 63% ee and 36% yield in the presence of Pd(OCOCF3)2, a ferrotane ligand, and TfOH cocatalyst.     

Ind(2)TiMe(2)]: a general catalyst for the intermolecular hydroamination of alkynes

[Ind(2)TiMe(2)] (Ind=indenyl) is a highly active and general catalyst for the intermolecular hydroamination of alkynes. It catalyzes the reaction of primary aryl-, tert-alkyl-, sec-alkyl-, and n-alkylamines with internal and terminal alkynes. In the case of unsymmetrically substituted 1-phenyl-2-alkylalkynes, the reactions occur with modest to excellent regioselectivities, whereby formation of the anti-Markovnikov regioisomers is favored. While the major product of hydroamination reactions of terminal arylalkynes is always the anti-Markovnikov isomer, alkylalkynes react with arylamines to preferably give the Markovnikov products. To achieve reasonable rates for the addition of sterically less hindered n-alkyl- and benzylamines to alkynes, these amines must be added slowly to the reaction mixtures. This behavior is explained by the fact that the catalytic cycle proposed on the basis of an initial kinetic investigation includes the possibility that the rate of the reaction increases with decreasing concentration of the employed amine. Furthermore, no dimerization of the catalytically active imido complex is observed in the hydroamination of 1-phenylpropyne with 4-methylaniline in the presence of [Ind(2)TiMe(2)] as catalyst. In general, a combination of [Ind(2)TiMe(2)]-catalyzed hydroamination of alkynes with subsequent reduction leads to the formation of secondary amines with good to excellent yields. Particularly impressive is that [Ind(2)TiMe(2)] makes it possible for the first time to perform the reactions of n-alkyl- and benzylamines with 1-phenylpropyne in a highly regioselective fashion.     

Rhodium-catalyzed intramolecular, anti-Markovnikov hydroamination. Synthesis of 3-arylpiperidines

The intramolecular anti-Markovnikov hydroamination of 1-(3-aminopropyl)vinylarenes in the presence of a readily available rhodium catalyst to form 3-arylpiperidines is reported. In contrast to intermolecular hydroamination of vinylarenes, which occurred in high yields in the presence of rhodium catalysts containing DPEphos, the intramolecular reaction occurred in high yield in the presence of [Rh(COD)(DPPB)]BF4 as catalyst. Reactants with substituents beta to the nitrogen occurred in high yield, and these reactions formed 3,5-disubstituted piperidines with high diastereomeric excess. The regiochemistry of these cyclizations contrasts with the regiochemistry of intramolecular hydroaminations catalyzed by lanthanide complexes, group III metal complexes, and platinum complexes, all of which have been reported to form cyclization products from Markovnikov addition.     

Anti-Markovnikov Hydroamination of Racemic Allylic Alcohols to Access Chiral γ-Amino Alcohols

A ruthenium-catalyzed formal anti-Markovnikov hydroamination of allylic alcohols for the synthesis of chiral γ-amino alcohols is presented. Proceeding via an asymmetric hydrogen-borrowing process, the catalysis allows racemic secondary allylic alcohols to react with various amines, affording enantiomerically enriched chiral γ-amino alcohols with broad substrate scope and excellent enantioselectivities (68 examples, up to >99 % ee).     

Amination of aromatic olefins with anilines: a new domino synthesis of quinolines

A new catalytic amination of aromatic olefins with anilines is presented. In a domino reaction, substituted quinoline derivatives are obtained in the presence of cationic rhodium complexes, such as [Rh(cod)2]BF4, and PPh3. Ethylbenzene is formed as a by-product in this new oxidative reaction. The first transition metal catalyzed anti-Markovnikov hydroamination of styrene with anilines occurs as a side reaction. Mechanistic investigations strongly support the regioselective oxidative amination of styrene as the key reaction step.     

A general study of [(eta5-Cp')2Ti(eta2-Me3SiC2SiMe3)]-catalyzed hydroamination of terminal alkynes: regioselective formation of Markovnikov and anti-Markovnikov products and mechanistic explanation (Cp'=C5H5, C5H4Et, C5Me5)

A general study of the regioselective hydroamination of terminal alkynes in the presence of [(eta5-Cp)2Ti(eta2-Me3SiC2SiMe3)] (1), [(eta5-CpEt)2Ti(eta2-Me3SiC2SiMe3)] (CpEt=ethylcyclopentadienyl) (2), and [(eta5-Cp*)2Ti(eta2-Me3SiC2SiMe3)] (Cp*=pentamethylcyclopentadienyl) (3) is presented. While aliphatic amines give mainly the anti-Markovnikov products, anilines and aryl hydrazines yield the Markovnikov isomer as main products. Interestingly, using aliphatic amines such as n-butylamine and benzylamine the different catalysts lead to a significant change in the observed regioselectivity. Here, for the first time a highly selective switch from the Markovnikov to the anti-Markovnikov product is observed simply by changing the catalyst. Detailed theoretical calculations for the reaction of propyne with different substituted anilines and tert-butylamine in the presence of [(eta5-C5H5)Ti(=NR)(NHR)] (R=4-C6H4X; X=H, F, Cl, CH3, 2,6-dimethylphenyl) reveal that the experimentally observed regioselectivity is determined by the relative stability of the corresponding pi-complexes 10. While electrostatic stabilization favors the Markovnikov performance for aniline, the steric repulsive destabilization disfavors the Markovnikov performance for tert-butylamine.     

Synthesis of tertiary alkyl amines from terminal alkenes: copper-catalyzed amination of alkyl boranes

A method for highly selective anti-Markovnikov hydroamination of terminal alkenes is reported. The one-pot procedure involves hydroboration of the alkene followed by a novel electrophilic amination of the alkyl borane catalyzed by an NHC-Cu complex. Terminal alkenes are successfully transformed into tertiary alkyl amines in the presence of a variety of functional groups in yields ranging from 80 to 97% with excellent regioselectivity. Results of a preliminary study of the reaction mechanism are also described.     

Chemoselective anti-Markovnikov hydroamination of α,β-ethylenic compounds with amines using montmorillonite clay

The catalytic activity of montmorillonite clays as a catalyst for the hydroamination of α,β-ethylenic compounds with amines was tested. Aniline and substituted anilines reacted with α,β-ethylenic compounds in the presence of catalytic amount of commercially available clay to afford exclusively anti-Markovnikov adduct in excellent yields. Aniline reacted with ethyl acrylate to yield only anti-Markovnikov adduct N-[2-(ethoxycarbonyl)ethyl]aniline (mono-addition product). No Markovnikov adduct (N-[1-(ethoxycarbonyl)ethyl]aniline and double addition product N,N-bis[2-(ethoxycarbonyl)ethyl]aniline were formed under selected reaction conditions. For a better exploitation of the catalytic activity in terms of increased activity and improved selectivity for the mono-addition product, the reaction parameters were optimized in terms of temperature, solvent, reactant mole ratio. Under optimized reaction conditions, montmorillonite clay K-10 showed a superior catalytic performance in the hydroamination of ethyl acrylate with aniline with a conversion of aniline to mono-addition product (almost 100% chemoselectivity) with a high rate constant 0.3414 min⁻¹ compared to the reported protocols. The dependence of conversion of aniline over different types of montmorillonite clays (K-10, K-20, K-30, Al-Pillared clay and untreated clay) has also been discussed. The activities of clay for the hydroamination of different aromatic and aliphatic amines have also been investigated. Under harsh reaction conditions (increased temperature and long reaction time) small amounts of di-addition products were observed. The kinetics data has been interpreted using the initial rate approach model.     

Anti-Markovnikov intermolecular hydroamination: a bis(amidate) titanium precatalyst for the preparation of reactive aldimines

[reaction: see text] A bulky bis(N-2',6'-diisopropylphenyl(phenyl)-amidate)titanium-bis(diethylamido) complex was identified as a highly active and regioselective precatalyst for the anti-Markovnikov hydroamination of a wide range of terminal alkyl alkynes with alkylamines. This titanium complex was fully characterized, including its X-ray crystal structure. The reactive aldimine products generated have been further elaborated using one-pot procedures to give substituted amines, aldehydes, and the isoquinoline framework.     

新型可回收高聚物负载手性配体在苯乙烯类化合物均相不对称双羟化反应中的催化性能研究

在多聚磷酸和AlCl3存在下，邻苯二甲酸酐与对二氟苯中通过Friedel-Crafts反应环化，以60％的产率生成1，4-二氟蒽醌．在碱性条件下，聚乙二醇单甲醚(HO-OPEG-OMe)与1，4-二氟蒽醌进行亲核单取代反应生成中间体F-AQN-OPEG-OMe，产率88％．然后F-AQN-OPEG-OMe与奎尼丁的锂盐再进行亲核取代反应，以91．7％的产率得到新型手性配体QD-AQN-OPEG-OMe．QD-AQN-OPEG-OMe与OsO4原位配位生成的均相催化剂在4种苯乙烯类化合物的不对称双羟化反应中表现出高的立体选择性(80％～94％ee)和催化活性(产率88％～96％)．催化活性和立体选择性与Sharpless手性配体(DHQD)2AQN相当．反应结束后，加入乙醚可使配体沉淀和回收，配体的回收率均在95％～97％之间．循环使用5次，催化剂的催化活性和立体选择性无明显改变．     

Ir(I)-catalyzed intermolecular regio- and enantioselective hydroamination of alkenes with heteroaromatic amines

A cationic Ir(I)-C(3)-TUNEPHOS complex catalyzed an intermolecular hydroamination of styrene derivatives with various heteroaromatic amines. The reaction gave Markovnikov products with perfect regioselectivity and good enantioselectivity under solvent-free conditions.     

Microwave-enhanced bismuth triflate-catalyzed epoxide opening with aliphatic amines

In the presence of a catalytic amount of Bi(OTf)₃·4H₂O and under microwave irradiation, neat mixtures of epoxides and amines afforded smoothly the corresponding 2-amino alcohols. A wide variety of aliphatic amines were reacted with cycloalkene oxide, styrene oxide, and stilbene oxide. The reaction proceeded rapidly and afforded the 2-amino alcohols in high up to quantitative yields. All products could be obtained without aqueous work-up by simple filtration.     

Oligomerization and hydroamination of terminal alkynes promoted by the cationic organoactinide compound [(Et2N)3U][BPh4

The three ancillary amido moieties in the cationic complex [(Et2N)3U][BPh4] are highly reactive and are easily replaced when the complex is treated with primary amines. The reaction of [(Et2N)3U][BPh4] with excess tBuNH2 allows the formation of the cationic complex [(tBuNH2)3(tBuNH)3U][BPh4]. X-ray diffraction studies on the complex indicate that three amido and three amine ligands are arranged around the cationic metal center in a slightly distorted octahedral mer geometry. The cationic complex reacts with primary alkynes in the presence of external primary amines to primarily afford the unexpected cis dimer and, in some cases, the hydroamination products are obtained concomitantly. The formation of the cis dimer is the result of an envelope isomerization through a metal-cyclopropyl cationic complex. In the reaction of the bulkier alkyne tBuC identical to CH with the cationic uranium complex in the presence of various primary amines, the cis dimer, one trimer, and one tetramer are obtained regioselectively, as confirmed by deuterium labeling experiments. The trimer and the tetramer correspond to consecutive insertions of an alkyne molecule into the vinylic CH bond trans to the bulky tert-butyl group. The reaction of (TMS) C identical to CH with the uranium catalyst in the presence of EtNH2 followed a different course and produced the gem dimer along with the hydroamination imine as the major product. However, when other bulkier amines were used (iPrNH2 or tBuNH2) both hydroamination isomeric imines Z and E were obtained. During the catalytic reaction, the E (kinetic) isomer is transformed into the most stable Z (thermodynamic) isomer. The unique reactivity of the alkyne (TMS) C identical to CH with the secondary amine Et2NH is remarkable because it afforded the trans dimer and the corresponding hydroamination enamine. The latter probably results from the insertion of the alkyne into a secondary metal-amide bond, followed by protonolysis.     

氟喹诺酮作为钯催化Heck反应有效配体的研究

研究了氟喹诺酮作为钯催化Heck反应的有效配体. 碘苯、溴苯和其它芳基卤衍生物与丙烯酸丁酯、苯乙烯等取代乙烯类化合物在钯和氟喹诺酮的催化下发生Heck反应. 讨论了配体、催化剂用量、碱和溶剂对Heck反应产率的影响. 该反应的最优化条件是: 钯源为Pd(OAc)2 (0.1 mol%), 诺氟沙星作为配体(0.2 mol%), K2CO3作为碱, DMA作为溶剂, 取代碘苯及溴苯和它们的衍生物与丙烯酸丁酯、苯乙烯等乙烯基化合物的反应均可以得到高收率的目标偶联产物.     

Gold-catalyzed hydrofunctionalization of allenes with nitrogen and oxygen nucleophiles and its mechanistic insight

A wide range of nucleophiles, such as amines and alcohols, reacted intermolecularly with various allenes in the presence of gold catalysts to give the corresponding hydrofunctionalization products in high yields. The intermolecular hydroamination of chiral allenes with aromatic and aliphatic amines proceeded with high to good enantioface selectivities to afford the corresponding chiral allylic amines. On the other hand, in the case of the intermolecular hydroalkoxylation of chiral allenes, no chirality transfer was observed. This marked contrast on the chirality transfer indicates that the mechanisms of gold-catalysis between hydroamination and hydroalkoxylation are different.     

用H2O2氧化苯乙烯合成苯甲酸

摘要：以30％H2O2做为氧化剂,钨酸钠与含O双齿有机配体(草酸)形成的络合物为催化剂,在无有机溶剂、无相转移剂的条件下,研究了苯乙烯氧化制苯甲酸的反应。研究结果表明,最佳反应条件为：苯乙烯100．0mmol,n(钨酸钠)：n(草酸)：n(苯乙烯)：n(30％H2O2)=2．0：3．2：100．0：440．0,于92℃反应24h,苯甲酸收率98．6％。用GC—MS跟踪了氧化过程中4种主要物质苯乙烯、1-苯基邻二醇、羟基苯乙酮及苯甲酸含量随反应时间的变化关系,提出了其主要氧化机理为苯乙烯经过环氧化反应、水解生成生成1-苯基邻二醇,1-苯基邻二醇再氧化为羟基苯乙酮、最后氧化为苯甲酸。     

Intermolecular hydroamination of vinyl arenes using tungstophosphoric acid as a simple and efficient catalyst

The intermolecular hydroamination of vinyl arene derivatives has been efficiently carried out using a tungstophosphoric acid (TPA) catalyst under solvent free and mild reaction conditions. The present protocol provides an environmentally benign, easy to handle and highly active solid acid catalyst for hydroamination of vinyl arenes. The catalyst yields both hydroamination and hydroarylation products and the selectivity mostly depends on the reaction conditions.     

Rhodium-catalyzed anti-Markovnikov addition of secondary amines to arylacetylenes at room temperature

An efficient method for synthesis of E-enamines by the anti-Markovnikov addition of secondary amines to terminal alkynes is described. The reaction of a variety of aryl- and heteroarylacetylenes proceeded at room temperature using a combination of a 8-quinolinolato rhodium complex and P(p-MeOC(6)H(4))(3) as a catalyst. The products were obtained as enamines by simple bulb-to-bulb distillation.