Intramolecular Aza‐Diels‐Alder Cyclization of a Dimerized Citral with Anilines Catalyzed by InCl3

A series of aza‐polycyles containing octahydroacridine core were prepared via an intramolecular aza‐Diels‐Alder reaction of a dimerized citral with various aromatic amines. This reaction is efficiently catalyzed by InCl₃ at ambient temperature to afford the corresponding cyclized products in moderate to good yields.     

Continuous Synthesis of Aryl Amines from Phenols Utilizing Integrated Packed‐Bed Flow Systems

Aryl amines are important pharmaceutical intermediates among other numerous applications. Herein, an environmentally benign route and novel approach to aryl amine synthesis using dehydrative amination of phenols with amines and styrene under continuous‐flow conditions was developed. Inexpensive and readily available phenols were efficiently converted into the corresponding aryl amines, with small amounts of easily removable co‐products (i.e., H₂O and alkanes), in multistep continuous‐flow reactors in the presence of heterogeneous Pd catalysts. The high product selectivity and functional‐group tolerance of this method allowed aryl amines with diverse functional groups to be selectively obtained in high yields over a continuous operation time of one week.     

Azabrendanes. III. Synthesis of stereoisomeric exo‐ and endo‐5‐acylaminomethyl‐exo‐2,3‐epoxybicyclo[2.2.1]heptanes and their reduction by lithium aluminum hydride

A number of stereoisomeric N‐[aryl(alkyl, cycloalkyl)carbonyl]‐exo(endo)‐5‐aminomethylbicyclo[2.2.1]hept‐2‐enes have been synthesized from bicyclo[2.2.1]hept‐2‐en‐exo(endo)‐5‐carbonitrile via reduction of the latter by lithium aluminum hydride and subsequent reactions of the resulting amines with aryl(alkyl, cycloalkyl)carbonyl chlorides and anhydrides. The direction of reaction of amides with peroxy acids does not depend on orientation of substituents in the bicyclic fragment: that is, for both exo‐ and endo‐isomers the epoxidations are completed by the formation of N‐[aryl(alkyl, cycloalkyl)carbonyl]‐exo(endo)‐5‐aminomethyl‐exo‐2,3‐epoxybicyclo[2.2.1] heptanes. The reduction of stereoisomeric epoxides by lithium aluminium hydride proceeds in different directions; that is, isomers with an exo‐oriented amido group form the substituted exo‐5‐alkylaminomethyl‐exo‐2,3‐epoxybicyclo[2.2.1]heptanes and the reactions of epoxides of endo‐amides are accompanied by intramolecular cyclization and completed by the formation of N‐[aryl(alkyl, cycloalkyl)]‐exo‐2‐hydroxy‐4‐azatricyclo[4.2.1.0^3,7]nonanes. The structures and stereochemical homogenity of the products have been confirmed by the analysis of ¹H and ¹³C NMR spectra, correlation spectroscopy, and nuclear Overhauser enhancement spectroscopy experiments. We discuss the behavior of epoxides and provide an analysis of the coefficients of the atomic orbitals in the molecular orbital–linear combination of atomic orbitals equation (AM1 method). © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:119–130, 2001     

Ring Opening of N‐Sulfonyl Aziridines by Amines in Silica‐Water

Ring opening reactions of N‐sulfonyl aziridines by primary and secondary amines in silica gel (SG)‐water system were achieved, which provided a mild, practical and environmentally benign method to synthesize mono‐ and bis‐sulfonyl substituted amines. When primary and secondary amines were used in excess, they reacted with N‐sulfonyl aziridines smoothly at room temperature, mainly affording 1:1 ring opening products. Reactions of primary amines with 2 equiv. of aziridines produced 2:1 ring opening products. Some 1:1 products can be cyclized with CS₂ to synthesize N‐sulfonyl cyclothioureas also in water.     

Copper-catalyzed amination of potassium aryl trifluoroborates using aqueous ammonia

The conversion of potassium aryl trifluoroborates containing different functionalities into the corresponding aryl amines using a catalytic amount of CuSO₄·5H₂O is described. The methodology uses water as a solvent under aerobic conditions to give the products in good yields.     

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.     

高选择性N-单甲基化芳香胺的合成

本文报道了一种高效专一性合成N-单甲基芳胺的方法。芳胺先与醋酐反应生成乙酰胺,再与碘甲烷在氢化钠作用下反应生成相应的N-甲基乙酰芳胺。在乙二醇中用酸水解高产率得到相应的N-单甲基芳胺。并将该方法用于药物中间体的合成。     

A Convenient Synthesis of 1‐Alkoxy‐2‐alkyl‐1,2‐dihydroisoquinoline‐3,4‐diones Utilizing the Reaction of 2‐(Dialkoxymethyl)phenyllithiums with Dimethyl Oxalate

A new and convenient method for the preparation of 1,2‐dihydroisoquinoline‐3,4‐diones with alkoxy and alkyl groups at the 4‐ and 3‐positions, respectively, using an easily operated three‐step sequence starting from 2‐(dialkoxymethyl)phenyl bromides has been developed. Thus, the starting materials are treated with BuLi to generate 2‐(dialkoxymethyl)phenyllithiums, which are allowed to react with (COOMe)₂ to give methyl 2‐(dialkoxymethyl)phenyl‐2‐oxoacetates. These are then transformed into the corresponding secondary amides by the reaction with primary amines. Treatment of these keto amides with a catalytic amount of TsOH?H₂O affords the desired products. In order to demonstrate the synthetic utility of these products, transformation of one of them into the corresponding isoquinoline‐1,3,4(2H)‐trione derivative by the oxidation with PCC was achieved.     

Unexpected regioselectivity in the palladium‐catalyzed reaction of silacyclobutanes with aryl iodides

The reaction of aryl iodides with 1,1‐diphenyl‐silacyclobutane in the presence of a catalytic amount of Pd(PPh₃)₄ affords unexpected ring‐opening adducts, 1‐ and 2‐propenyl(triaryl)‐silanes, in good yields. On the other hand, the PdCl₂(PhCN)₂‐catalyzed reaction of 1,1‐diphenylsilacyclobutanes with aryl halides gives ­unexpected products, triarylsilanols, after ­hydrolysis in moderate yields. The catalysis involves the reaction of aryl–palladium intermediates with silacyclobutanes along with ­regioselective aryl–silicon bond formation. Copyright © 2001 John Wiley & Sons, Ltd.     

Suzuki Coupling of Cyclopropylboronic Acid With Aryl Halides Catalyzed by a Palladium–Tetraphosphine Complex

The tetraphosphine all‐cis‐1,2,3,4‐tetrakis(diphenylphosphinomethyl)cyclopentane (Tedicyp) in combination with [Pd(C₃H₅)Cl]₂ affords a very efficient catalyst for the coupling of cyclopropylboronic acid with aryl bromides and aryl chlorides. Higher reactions rates were observed with aryl bromides than with aryl chlorides; however, even in the presence of 1–0.4% of catalyst, a few aryl chlorides gave the coupling products in good yields. A wide variety of substituents such as alkyl, methoxy, trifluoromethyl, acetyl, benzoyl, formyl, carboxylate, nitro, and nitrile on the aryl halides are tolerated. The coupling reaction of sterically very congested aryl bromides such as bromomesitylene or 2,4,6‐triisopropylbromobenzene also proceeds in good yields.     

Facile N-arylation of amines and sulfonamides

[reaction: see text] A facile, transition-metal-free N-arylation procedure for amines and sulfonamides has been developed, which affords good to excellent yields of arylated products under very mild reaction conditions. A methoxy-substituted aryl triflate affords N-arylated products in high yields with excellent regioselectivity. This chemistry tolerates a variety of functional groups.     

Stereoselective synthesis of 2-alkenylaziridines and 2-alkenylazetidines by palladium-catalyzed intramolecular amination of alpha- and beta-amino allenes.

Whereas palladium-catalyzed reaction of N-arylsulfonyl-alpha-amino allenes with an aryl iodide (4 equiv) in the presence of potassium carbonate (4 equiv) in DMF at around 70 degrees C affords the corresponding 3-pyrroline derivatives, the reaction in refluxing 1,4-dioxane under otherwise identical conditions yields exclusively or most predominantly the corresponding 2-alkenylaziridines bearing an aryl group on the double bond. Similarly, N-arylsulfonyl-beta-amino allenes can be also cyclized into the corresponding alkenylazetidines bearing a 2,4-cis-configuration under palladium-catalyzed cyclization conditions in DMF.     

Selenium‐Containing Heterocycles from Isoselenocyanates: Synthesis of 5‐Amino‐2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐selones

The reaction of S‐methylisothiosemicarbazide hydroiodide (=S‐methyl hydrazinecarboximidothioate hydroiodide; 1 ), prepared from thiosemicarbazide by treatment with MeI in EtOH, and aryl isoselenocyanates 5 in CH₂Cl₂ affords 3H‐1,2,4‐triazole‐3‐selone derivatives 7 in good yield (Scheme 2, Table 1). During attempted crystallization, these products undergo an oxidative dimerization to give the corresponding bis(4H‐1,2,4‐triazol‐3‐yl) diselenides 11 (Scheme 3). The structure of 11a was established by X‐ray crystallography.     

Stereospecific 2-vinylcyclohexanol formation via internal attack of an allylsilane moiety on an aldehyde group

Acid catalyzed cyclization of ($\text{E}$)-HCO-(CH₂)-₄-CH=C(Me)-CH(SPh)SiMe₃ affords $\text{cis}$-2-substituted cyclohexanol, while ($\text{Z}$) compound affords the $\text{trans}$ isomer. Those cyclized products are transformed to the corresponding α-methyl γ-lactones.     

Fast tin-free hydrodehalogenation and reductive radical cyclization reactions: a new reduction process

The photostimulated reactions of several aryl and alkyl chlorides and bromides with the monoanion of reduced ethyl benzoate 5H furnish the reduced products in high yields. If the aryl moieties have suitable double bonds, the cyclized reduced products are obtained in high yields. The photostimulated reaction of 1-allyloxy-2-bromobenzene (1a) with 5H affords 3-methyl-2,3-dihydro-benzofuran (2a) in 97% yield. When 1-allyloxy-2-chlorobenzene (1b) is used, the yield of 2a is only 55%, which increases up to 91% when acetone enolate ion is added to the reaction mixture as entrainment reagent. With diallyl-(2-bromophenyl)amine (3a), and 2-allyloxy-1-halonaphthalenes (chloro, 4b, and bromo, 4a) the cyclized reduced products are obtained in yields above 96%. By competition experiments, 5H reacts ca. 5 times faster with 1-naphthyl radicals than benzenethiolate ions do, which is near the diffusion limit rate.     

Tuning the Reactivity of Isocyano Group: Synthesis of Imidazoles and Imidazoliums from Propargylamines and Isonitriles in the Presence of Multiple Catalysts

The reaction of propargyl amines with tert‐butylisonitrile in the presence of a catalytic amount of both Yb(OTf)₃ and AgOTf afforded imidazoles, whereas the same reaction with primary and secondary alkylisonitriles, as well as arylisonitriles, in the presence of three metal salts [Yb(OTf)₃/AgOTf/KOTf] resulted in the 1,3,4,5‐tetrasubstituted imidazoliums in excellent yields. Both chiral amines and chiral isonitriles can be used to provide corresponding chiral heterocycles without racemization. In this multiple catalytic system, Yb(OTf)₃ catalyzed the insertion of isonitriles to the N? H bond of amines, AgOTf catalyzed the 5‐exo‐dig cyclization of the resulting amidine nitrogen to the tethered triple bond, and KOTf promoted the salt metathesis, thus providing at the same time the counterion to the imidazolium. Against common knowledge, the isocyano group acted in these reactions as a polarized triple bond instead of conventional carbene‐like function.     

A versatile method for the synthesis of diaryl and alkyl aryl ketones via palladium‐catalysed cross‐coupling reaction of arylboronic acids with acyl chlorides

An efficient catalytic system using 1‐benzyl‐4‐aza‐1‐azoniabicyclo[2.2.2]octane chloride and PdCl₂ was developed for the cross‐coupling reaction of arylboronic acids with acyl chlorides. The catalytic amount of this homogeneous catalytic system affords the corresponding diaryl and alkyl aryl ketones in good to excellent yields under mild reaction conditions. Copyright © 2015 John Wiley & Sons, Ltd.     

Well-defined NHC–Pd(II)–Im (NHC=N-heterocyclic carbene; Im=1-methylimidazole) complex catalyzed C–N coupling of primary amines with aryl chlorides

We report herein a well-defined NHC–Pd(II)–Im (NHC=N-heterocyclic carbene; Im=1-methylimidazole) complex catalyzed C–N coupling of primary amines with aryl chlorides. Under the optimal reaction conditions, a variety of primary amines can be coupled with aryl chlorides to give the amination products in good to high yields within 4 h. It is worthy of noting here that the NHC–Pd(II)–Im complex showed especially high catalytic activity toward challenging sterically hindered substrates including both of aryl amines and aryl chlorides. In addition, alkyl amines were also proved to be suitable reaction partners to give the corresponding amination products in good to high yields.     

Substrate‐Controlled Product Divergence: Conversion of CO2 into Heterocyclic Products

Substituted epoxy alcohols and amines allow substrate‐controlled conversion of CO₂ into a wide range of heterocyclic structures through different mechanistic manifolds. This new approach results in an unusual scope of CO₂‐derived products by initial activation of CO₂ through either the amine or alcohol unit, thus providing nucleophiles for intramolecular epoxy ring opening under mild reaction conditions. Control experiments support the crucial role of the amine/alcohol fragment in this process with the nucleophile‐assisted ring‐opening step following an S_Ni pathway, and a 5‐exo‐tet cyclization, thus leading to heterocyclic scaffolds.     

Synthesis and applications of a new palladacycle as a high active catalyst in the Suzuki couplings

The reaction of biphenyl-based phosphine P(o-C₆H₄Me)Ph₂ (1) with Pd(OAc)₂ in toluene affords the air and water stable palladacycle (2) as a binuclear compound which has been characterized by multi-nuclear NMR spectroscopy and elemental analysis as a mixture of cis and trans isomers with relative intensity of 1:3, respectively. This palladacycle is a highly efficient catalyst precursor for the coupling of aryl boronic acids and aryl halides. Both activated and deactivated aryl bromides and chlorides are efficiently coupled in the presence of 2 to furnish the corresponding cross-coupled products in excellent yields, and a wide variety of functional groups are tolerated in aryl halides. This methodology has also been extended for the coupling of bromoarylphosphines and bromoarylphosphine oxides with aryl boronic acids for the generation of hindered corresponding products.