An improved protocol for the selective hydroaminomethylation of arylethylenes

The hydroaminomethylation of arylethylenes with anilines proceeds under mild conditions in the presence of [Rh(cod)₂BF₄] and dppf as catalyst system to give the corresponding branched amphetamine derivatives in good selectivity and yield.     

A Multicatalytic Approach to the Hydroaminomethylation of α‐Olefins

We report an approach to conducting the hydroaminomethylation of diverse α‐olefins with a wide range of alkyl, aryl, and heteroarylamines at relatively low temperatures (70–80 °C) and pressures (1.0–3.4 bar) of synthesis gas. This approach is based on simultaneously using two distinct catalysts that are mutually compatible. The hydroformylation step is catalyzed by a rhodium diphosphine complex, and the reductive amination step, which is conducted as a transfer hydrogenation with aqueous, buffered sodium formate as the reducing agent, is catalyzed by a cyclometallated iridium complex. By adjusting the ratio of CO to H₂, we conducted the reaction at one atmosphere of gas with little change in yield. A diverse array of olefins and amines, including hetreroarylamines that do not react under more conventional conditions with a single catalyst, underwent hydroaminomethylation with this new system, and the pharmaceutical ibutilide was prepared in higher yield and under milder conditions than with a single catalyst.     

Highly selective hydroaminomethylation of internal alkenes to give linear amines

The application of phenoxaphosphino-modified Xantphos-type ligands (1-9) in the rhodium-catalyzed hydroaminomethylation of internal olefins to give linear amines is reported. Excellent chemo- and regioselectivities have been obtained through the use of 0.1 mol % [Rh(cod)2]BF(4)/0.4 mol % xantphenoxaphos (1), providing a practical and environmentally attractive synthetic route for the preparation of amines from internal alkenes. For the first time, both functionalized internal olefins and mixtures of internal and terminal olefins have been converted highly selectively into linear amines. Investigations of the effects of the calculated natural bite angles of ligands on hydroaminomethylation shows that the regioselectivity for the linear product follows a similar trend to that seen in the hydroformylation of internal alkenes with the aid of these ligands. Hydroaminomethylation and each of its individual steps were monitored by high-pressure infrared spectroscopy. The results suggest that hydroaminomethylations take place by a sequential isomerization/hydroformylation/amination/hydrogenation pathway.     

The First Efficient Hydroaminomethylation with Ammonia: With Dual Metal Catalysts and Two-Phase Catalysis to Primary Amines

Primary and unbranched secondary amines are obtained by the highly selective hydroaminomethylation of olefins with ammonia [Eq. (a)]. The selectivity is readily controlled with a new dual Rh/Ir catalyst in a two-phase system.     

Asymmetric Petasis Borono‐Mannich Allylation Reactions Catalyzed by Chiral Biphenols

Chiral biphenols catalyze the asymmetric Petasis borono‐Mannich allylation of aldehydes and amines through the use of a bench‐stable allyldioxaborolane. The reaction proceeds via a two‐step, one‐pot process and requires 2–8 mole % of 3,3′‐Ph₂‐BINOL as the optimal catalyst. Under microwave heating the reaction affords chiral homoallylic amines in excellent yields (up to 99 %) and high enantioselectivies (er up to 99:1). The catalytic reaction is a true multicomponent condensation reaction whereas both the aldehyde and the amine can possess a wide range of structural and electronic properties. Use of crotyldioxaborolane in the reaction results in stereodivergent products with anti‐ and syn‐diastereomers both in good diastereoselectivities and enantioselectivities from the corresponding E‐ and Z‐borolane stereoisomers.     

Metal and organo-catalysed asymmetric hydroaminomethylation of styrenes

A new protocol that enables asymmetric hydroaminomethylation of styrenes to afford chiral amines has been developed. Catalysed by an Rh-phosphine species and a chiral phosphoric acid, styrenes are converted into β-chiral amines with good enantioselectivities under syngas in the presence of an amine and Hantzsch ester. The reaction involves two key steps, hydroformylation and reductive amination, with the former catalysed by the Rh species whilst the latter by the phosphoric acid.     

苯乙烯与4-氨基苯酚的氢氨甲基化反应研究北大核心CSCD

氢氨甲基化反应(HAM)是由简单烯烃、胺和合成气一锅法合成有价值胺的方法,具有较高的原子经济效率.然而,4-氨基苯酚作为一种特殊的反应底物,因其同时具有羟基和胺基官能团,在羰基化反应过程中能够选择性地在不同位点发生反应获得不同的产物.因此,我们系统研究了4-氨基苯酚与烯烃的HAM,通过筛选反应参数,确定了最优反应条件,并通过调控添加剂种类,选择性地在4-氨基苯酚的不同活性位点发生反应.结果表明,以甲醇为溶剂,三(3-甲氧基苯基)膦为配体,RhCl(PPh_(3))_(3)为催化剂前驱体,合成气压力4 MPa(H_(2)∶CO=3∶1),反应温度100℃,反应时间20 h时,该催化体系具有最高的反应活性.当以CH3COOH作为添加剂时,选择性的4-氨基苯酚的胺基官能团发生氢氨甲基化反应得到产物4-[(2-苯丙基)氨基]苯酚,收率为82%;当以DBU作为添加剂时,得到苯乙酮产物,收率为92%.最后,提出了该反应可能的机理,为4-氨基苯酚的选择性反应提供理论依据.     

Direct Catalytic Addition of Alkylnitriles to Aldehydes by Transition‐Metal/NHC Complexes

Direct catalytic addition of alkylnitriles to aldehydes allows for an atom‐economical access to β‐hydroxynitriles under proton transfer conditions. Direct use of alkylnitriles as pronucleophiles has been hampered due to their low acidity resulting in an inability to generate α‐cyano carbanions in a catalytic manner. A transition metal/N‐heterocyclic carbene (NHC) complex prepared from [{Rh(OMe)(cod)}₂] and an imidazolium‐based carbene was identified as an effective catalyst to promote the reaction with as little as 1.25 mol % of catalyst loading. The corresponding Rh complex, derived from chiral triazolium salt, rendered the reaction enantioselective, albeit with moderate enantioselectivity.     

Rhodium-catalyzed ring-opening reactions of N-boc-azabenzonorbornadienes with amine nucleophiles

In the presence of a rhodium catalyst (5 mol %) generated in situ from [Rh(cod)Cl](2) and (S,S')-(R,R')-C(2)-ferriphos (4a), the asymmetric ring-opening reaction of azabenzonorbornadienes (1a-m) with various aliphatic and aromatic amines (2a-l) proceeded with high enantioselectivity (up to >99% ee) to give the corresponding 1,2-diamine derivatives 3 in high yields. In the specific case of pyrrolidine as nucleophile, Et(3)NHCl was necessary as an additive for good reactivity and enantioselectivity. Additionally, a practical protocol was developed for the ring-opening of 1a with volatile amines at elevated temperatures and standard pressure, using R(2)NH(2)I and i-Pr(2)NEt. The experimental results showed that the nature of the chiral ligand has the significant impact on the reactivity of the catalyst and the use of excess amount (2.2 eq to Rh) of the chiral ligand plays an important role to improve the enantioselectivity in the present asymmetric reaction.     

Highly efficient AgNO3‐catalyzed approach to 2‐(benzo[d]azol‐2‐yl)phenols from salicylaldehydes with 2‐aminothiophenol, 2‐aminophenol and benzene‐1,2‐diamine

A new, convenient and efficient AgNO₃‐catalyzed strategy for the preparation of 2‐(benzo[d]azol‐2‐yl)phenol derivatives in good to excellent yields (63–98%) is described. The reaction proceeds via condensation/intramolecular nucleophilic addition/oxidation process between substituted salicylaldehydes and 2‐aminothiophenol, 2‐aminophenol or benzene‐1,2‐diamine under mild reaction conditions. Notably, this reaction utilizes cheap AgNO₃ as a readily available and low‐cost benign oxidant at low catalyst loadings with excellent functional group tolerance.     

Scope and limitations of the Pd/BINAP-catalyzed amination of aryl bromides

Mixtures of Pd(2)(dba)(3) or Pd(OAc)(2) and BINAP catalyze the cross-coupling of amines with a variety of aryl bromides. Primary amines are arylated in high yield, and certain classes of secondary amines are also effectively transformed. The process tolerates the presence of several functional groups including methyl and ethyl esters, enolizable ketones, and nitro groups provided that cesium carbonate is employed as the base. Most reactions proceed to completion with 0.5-1.0 mol % of the palladium catalyst; in some cases, catalyst levels as low as 0.05 mol % Pd may be employed. Reactions are considerably faster if Pd(OAc)(2) is employed as the precatalyst, and the order in which reagents are added to the reaction has a substantial effect on reaction rate. It is likely that the catalytic process proceeds via bis(phosphine)palladium complexes as intermediates. These complexes are less prone to undergo undesirable side reactions which lead to diminished yields or catalyst deactivation than complexes of the corresponding monodentate triarylphosphines.     

2,2,2‐Trifluoroacetophenone as an Organocatalyst for the Oxidation of Tertiary Amines and Azines to N‐Oxides

A cheap, mild and environmentally friendly oxidation of tertiary amines and azines to the corresponding N‐oxides is reported by using polyfluoroalkyl ketones as efficient organocatalysts. 2,2,2‐Trifluoroacetophenone was identified as the optimum catalyst for the oxidation of aliphatic tertiary amines and azines. This oxidation is chemoselective and proceeds in high‐to‐quantitative yields utilizing 10 mol % of the catalyst and H₂O₂ as the oxidant.     

Cation-exchange resin as an efficient hetero-geneous catalyst for one-pot three-component synthesis of 2,3-dihydro-4(1H)-quinazolinones

Various mono- and disubstituted 2,3-dihydro-4(1H)-quinazolinones were synthesized efficiently by a one-pot three-component condensation of isatoic anhydride, aromatic aldehydes, and ammonium salts or primary amines using a strong acidic cation-exchange resin as the catalyst in EtOH–H₂O solution. The catalyst is cheap, efficient, stable, and reusable under the reaction conditions. The novel method offers several advantages, such as excellent yields, environmentally friendly reaction media, and simple procedure.     

Phosphine‐ and Hydrogen‐Free: Highly Regioselective Ruthenium‐Catalyzed Hydroaminomethylation of Olefins

A highly regioselective ruthenium‐catalyzed hydroaminomethylation of olefins is reported. Using easily available trirutheniumdodecacarbonyl an efficient sequence consisting of a water‐gas shift reaction, hydroformylation of olefins, with subsequent imine or enamine formation and final reduction is realized. This novel procedure is highly practical (ligand‐free, one pot) and economic (low catalyst loading and inexpensive metal). Bulk industrial as well as functionalized olefins react with various amines to give the corresponding tertiary amines generally in high yields (up to 92 %), excellent regioselectivities (n/iso>99:1), and full chemoselectivity in favor of terminal olefins.     

氧化铝负载的银纳米颗粒高选择性催化合成亚胺(英)

The oxidative dehydrogenation of alcohols to aldehydes catalyzed by Ag nanoparticles supported on Al₂O₃ was studied.The catalyst promoted the direct formation of imines by tandem oxidative dehydrogenation and condensation of alcohols and amines.The reactions were performed under mild conditions and afforded the imines in high yield（up to 99%） without any byproducts other than H₂O.The highest activity was obtained over 5 wt%Ag/Al₂O₃ in toluene with air as oxidant.The reactions were also performed under oxidant-free conditions where the reaction was driven to the product side by the production of H₂ in the gas phase.The use of an efficient and selective Ag catalyst for the oxidative dehydrogenation of alcohol in the presence of amines gives a new green reaction protocol for imine synthesis.     

Highly regioselective hydroaminomethylation of terminal olefins to linear amines using Rh complexes with a Tetrabi phosphorus ligand

A highly regioselective hydroaminomethylation of terminal olefins catalyzed by Rh complexes with 2, 2′, 6, 6′‐tetrakis ((diphenylphosphino)methyl)‐1, 1′‐biphenyl (Tetrabi) ligand has been developed. Up to 99 % amine selectivity, 168 linear/branched amine product ratio (n/i), and 97.4 % linear amine yield has been obtained at a substrate/rhodium precursor ratio (S/Rh) of 1000 with this methodology. The turnover number was achieved 6930 at 10000 S/Rh ratio, and the n/i can reach up to >525. Several different olefins and secondary amines have been applied successfully with high chemoselectivity (99 %), yield (>98 %), and regioselectivity (>120).     

Branched Tertiary Amines from Aldehydes and α-Olefins by Combined Multiphase Tandem Reactions

This study presents the transformation of olefins to branched amines by combining a hydroformylation/aldol condensation tandem reaction with the reductive amination in a combined multiphase system that can be recycled 9 times. The products are branched amines that are precursors for surfactants. Since the multiphase hydrofomylation/aldol condensation system has already been studied, the first step was to develop the partial hydrogenation of unsaturated aldehydes together with a subsequent reductive amination. The rhodium/phosphine catalyst is immobilized in a polar polyethylene phase which separates from the product phase after the reaction. Reaction and catalyst recycling are demonstrated by the conversion of the C₁₄-aldehyde 2-pentylnonenal with the dimethylamine surrogate dimethylammonium dimethylcarbamate to the corresponding tertiary amine with yields up to 88 % and an average rhodium leaching of less than 0.1 % per recycling run. Furthermore, the positive influence of a Bronsted acid and carbon monoxide on the selectivity are discussed. Finally, the two PEG based systems have been merged in one recycling approach, by using the product phase of the hydroformylation aldol condensation reaction for the reductive amination reaction. The yields are stable during a nine recycling runs and the leaching low with 0.09 % over the two recycling stages.     

Direct Synthesis of Protoberberine Alkaloids by Rh‐Catalyzed C−H Bond Activation as the Key Step

A one‐pot reaction of substituted benzaldehydes with alkyne–amines by a Rh‐catalyzed C?H activation and annulation to afford various natural and unnatural protoberberine alkaloids is reported. This reaction provides a convenient route for the generation of a compound library of protoberberine salts, which recently have attracted great attention because of their diverse biological activities. In addition, pyridinium salt derivatives can also be formed in good yields from α,β‐unsaturated aldehydes and amino–alkynes. This reaction proceeds with excellent regioselectivity and good functional group compatibility under mild reaction conditions by using O₂ as the oxidant.     

Synthesis of biologically active amines via rhodium-bisphosphite-catalyzed hydroaminomethylation

[reaction: see text] We report the use of a highly regioselective rhodium-bisphosphite catalyst for olefin hydroaminomethylation. This catalyst system was successfully applied in the synthesis of two biologically active tertiary amines, ibutilide and aripiprazole.     

“One pot” synthesis of tertiary amines: Ru(II) catalyzed direct reductive N-benzylation of imines with benzyl bromide derivatives

The direct reductive N-benzylation of imines by reaction with benzyl bromide derivatives, in the presence of [RuCl₂(p-cymene)]₂ catalyst and PhSiH₃, is performed under mild conditions without additional base. This reaction proceeds by a tandem imine hydrosilylation/nucleophilic substitution with benzyl bromide derivatives to result the tertiary amines.