Copper‐Catalyzed 8‐Amido Chelation‐Induced Remote C−H Amination of Quinolines

A copper‐catalyzed 8‐amide chelation‐induced remote C?H amination of quinolines has been developed. This direct amination with readily available azodicarboxylates proceeded with perfect C5‐regioselectivity offering amino‐substituted 8‐aminoquinolines, important bioactive molecular scaffolds, in very high yields (up to 96 %). A single‐electron transfer (SET)‐mediated mechanism with k_H/k_D=1.1 was proposed after trapping of the radical intermediate.     

Palladium‐Catalyzed Amination of Aryl Sulfides with Anilines

A combination of a palladium–NHC catalyst and potassium hexamethyldisilazide enables the amination of aryl sulfides with anilines to afford a wide variety of diarylamines. The reaction conditions are versatile enough for the reaction of even bulky ortho‐substituted aryl sulfides. This amination can be applied to the modular synthesis of N‐aryl carbazoles from the corresponding ortho‐bromothioanisoles. As aryl sulfoxides undergo extended Pummerer reactions to afford ortho‐substituted aryl sulfides, the Pummerer products are thus useful substrates for the amination to culminate in efficient syntheses of a 2‐anilinobenzothiophene and an indole as proof‐of‐principle of the utility of the extended Pummerer reaction/amination cascade.     

Tetrahydro‐1,5‐benzoxazepines and tetrahydro‐1H‐1,5‐benzodiazepines by a tandem reduction‐reductive amination reaction

A tandem reduction‐reductive amination reaction has been applied to the synthesis of (±)‐4‐alkyl‐2,3,4,5‐tetrahydro‐1,5‐benzoxazepines and (±)‐4‐alkyl‐1‐benzoyl‐2,3,4,5‐tetrahydro‐1H‐1,5‐benzodiazepines. The nitro aldehydes and ketones required for 1,5‐benzoxazepine ring closures were prepared by nucleophilic aromatic substitution of the alkoxides from several 3‐buten‐1‐ol derivatives with 2‐fluoro‐1‐nitrobenzene followed by ozonolysis. Precursors for the 1,5‐benzodiazepines were prepared by similar addition of N‐(3‐butenyl)benzamide anions to 2‐fluoro‐1‐nitrobenzene followed by ozonolysis. Catalytic hydrogenation of the nitro carbonyl compounds using 5% palladium‐on‐carbon in methanol then gave the target heterocycles by a tandem reduction‐reductive amination sequence. The 1,5‐benzoxazepines were isolated in high yield following chromatographic purification; the 1,5‐benzodiazepines were isolated as solids directly from the hydrogenation mixture and possessed differentiated functionality on the two nitrogen atoms.     

Tandem Hydroformylation/Reductive Amination of 3‐Allyl‐2‐methylquinazolin‐4(3H)‐one

The 3‐allyl‐2‐methylquinazolin‐4(3H)‐one ( 1 ), a model functionalized terminal olefin, was submitted to hydroformylation and reductive amination under optimized reaction conditions. The catalytic carbonylation of 1 in the presence of Rh catalysts complexed with phosphorus ligands under different reaction conditions afforded a mixture of 2‐methyl‐4‐oxoquinazoline‐3(4H)‐butanal ( 2 ) and α,2‐dimethyl‐4‐oxoquinazoline‐3(4H)‐propanal ( 3 ) as products of ‘linear’ and ‘branched’ hydroformylation, respectively (Scheme 2). The hydroaminomethylation of quinazolinone 1 with arylhydrazine derivatives gave the expected mixture of [(arylhydrazinyl)alkyl]quinazolinones 5 and 6 , besides a small amount of 2 and 3 (Scheme 3). The tandem hydroformylation/reductive amination reaction of 1 with different amines gave the quinazolinone derivatives 7 – 10 . Compound 10 was used to prepare the chalcones 11a and 11b and pyrazoloquinazolinones 12a and 12b (Scheme 4).     

Selective Monoarylation of Primary Amines Using the Pd‐PEPPSI‐IPentCl Precatalyst

A single set of reaction conditions for the palladium‐catalyzed amination of a wide variety of (hetero)aryl halides using primary alkyl amines has been developed. By combining the exceptionally high reactivity of the Pd‐PEPPSI‐IPent^Cl catalyst (PEPPSI=pyridine enhanced precatalyst preparation, stabilization, and initiation) with the soluble and nonaggressive sodium salt of BHT (BHT=2,6‐di‐tert‐butyl‐hydroxytoluene), both six‐ and five‐membered (hetero)aryl halides undergo efficient and selective amination.     

Cobalt‐Catalyzed Electrophilic Amination of Aryl‐ and Heteroarylzinc Pivalates with N‐Hydroxylamine Benzoates

Aryl‐ and heteroarylzinc pivalates can be aminated with O‐benzoylhydroxylamines at 25 °C within 2–4 h in the presence of 2.5–5.0 % CoCl₂?2 LiCl to furnish the corresponding tertiary arylated or heteroarylated amines in good yields. This electrophilic amination also provides access to diarylamines and aryl(heteroaryl)amines. A new tuberculosis drug candidate (Q203) was prepared in six steps and 56 % overall yield by using this cobalt‐catalyzed amination as the key step.     

PEG‐4000‐promoted palladium‐catalyzed N‐allylation in water: aminonaphthalene as an example

An environmentally friendly, efficient catalytic process using palladium associated with ligands in a PEG4000–water system leading to N‐allylation was described in this study. PEG‐4000 was found to improve the palladium‐catalyzed allylic amination of allylic acetates with aminonaphthalenes and gave overall good to high yields of the corresponding N‐allylic aminonaphthalenes. Copyright © 2012 John Wiley & Sons, Ltd.     

Enantioselective Allylic Amination of Morita‐Baylis‐Hillman Acetates Catalyzed by Chiral Thiourea‐Phosphine

The enantioselective allylic amination of Morita‐Baylis‐Hillman acetates catalyzed by chiral cyclohexane‐based thiourea‐phosphine catalysts was investigated. In the presence of 20 mol% rosin‐derived thiourea‐phosphine 3j , the chiral amines were obtained in up to 88% yield and up to 85% ee.     

Regio‐ and Enantioselective Synthesis of N‐Allylindoles by Iridium‐Catalyzed Allylic Amination/Transition‐Metal‐Catalyzed Cyclization Reactions

Regio‐ and enantioselective synthesis of N‐allylindoles was realized through an iridium‐catalyzed asymmetric allylic amination reaction with 2‐alkynylanilines and subsequent transition‐metal‐catalyzed cyclization reactions. The highly enantioenriched allylic amines prepared from Ir‐catalysis were treated with catalytic amount of NaAuCl₄ ? 2 H₂O or PdCl₂ providing various substituted N‐allylindoles in excellent yields and enantioselectivities.     

Solvent‐Enhanced Diastereo‐ and Regioselectivity in the PdII‐Catalyzed Synthesis of Six‐ and Eight‐Membered Heterocycles via cis‐Aminopalladation

The Pd^II‐catalyzed intramolecular oxidative cyclization of tosyl‐protected cis‐ and trans‐N‐allyl‐2‐aminocyclohexanecarboxamides was examined, and efficient syntheses of cyclohexane‐fused pyrimidin‐4‐ones and 1,5‐diazocin‐6‐ones were developed. In the course of the research, a marked solvent effect was observed on both the regio‐ and diastereoselectivity. Additionally, a novel Pd^II‐mediated domino oxidation, oxidative amination reaction was discovered. Our experimental and theoretical findings suggest that the reactions proceed via a cis‐aminopalladation mechanism.     

Application of a Palladium‐Catalyzed C−H Functionalization/Indolization Method to Syntheses of cis‐Trikentrin A and Herbindole B

We describe herein formal syntheses of the indole alkaloids cis‐trikentrin A and herbindole B from a common meso‐hydroquinone intermediate prepared by a ruthenium‐catalyzed [2+2+1+1] cycloaddition that has not been used previously in natural product synthesis. Key steps include a sterically demanding Buchwald–Hartwig amination as well as a unique C(sp³)?H amination/indole formation. Studies toward a selective desymmetrization of the meso‐hydroquinone are also reported.     

Artificial Multi‐Enzyme Networks for the Asymmetric Amination of sec‐Alcohols

Various artificial network designs that involve biocatalysts were tested for the asymmetric amination of sec‐alcohols to the corresponding α‐chiral primary amines. The artificial systems tested involved three to five redox enzymes and were exemplary of a range of different sec‐alcohol substrates. Alcohols were oxidised to the corresponding ketone by an alcohol dehydrogenase. The ketones were subsequently aminated by employing a ω‐transaminase. Of special interest were redox‐neutral designs in which the hydride abstracted in the oxidation step was reused in the amination step of the cascade. Under optimised conditions up to 91 % conversion of an alcohol to the amine was achieved.     

Highly Regio‐ and Enantioselective Synthesis of N‐Substituted 2‐Pyridones: Iridium‐Catalyzed Intermolecular Asymmetric Allylic Amination

The first iridium‐catalyzed intermolecular asymmetric allylic amination reaction with 2‐hydroxypyridines has been developed, thus providing a highly efficient synthesis of enantioenriched N‐substituted 2‐pyridone derivatives from readily available starting materials. This protocol features a good tolerance of functional groups in both the allylic carbonates and 2‐hydroxypyridines, thereby delivering multifunctionalized heterocyclic products with up to 98 % yield and 99 % ee.     

N‐Heterocyclic Carbene Iron(III) Porphyrin‐Catalyzed Intramolecular C(sp3)–H Amination of Alkyl Azides

Metal‐catalyzed intramolecular C?H amination of alkyl azides constitutes an appealing approach to alicyclic amines; challenges remain in broadening substrate scope, enhancing regioselectivity, and applying the method to natural product synthesis. Herein we report an iron(III) porphyrin bearing axial N‐heterocyclic carbene ligands which catalyzes the intramolecular C(sp³)–H amination of a wide variety of alkyl azides under microwave‐assisted and thermal conditions, resulting in selective amination of tertiary, benzylic, allylic, secondary, and primary C?H bonds with up to 95 % yield. 14 out of 17 substrates were cyclized selectively at C4 to give pyrrolidines. The regioselectivity at C4 or C5 could be tuned by modifying the reactivity of the C5–H bond. Mechanistic studies revealed a concerted or a fast re‐bound mechanism for the amination reaction. The reaction has been applied to the syntheses of tropane, nicotine, cis‐octahydroindole, and leelamine derivatives.     

Heterogeneous Aromatic Amination of Aryl Halides with Arylamines in Water with PS‐PEG Resin‐Supported Palladium Complexes

Catalytic aromatic amination is achieved in water under heterogeneous conditions by the use of immobilized palladium complexes coordinated with the amphiphilic polystyrene‐poly(ethylene glycol) resin‐supported di(tert‐butyl)phosphine ligand. Aromatic amination of aryl halides with diphenylamine and N,N‐double arylation of anilines with bromobenzene were found to proceed in water with broad substrate tolerance to give the triarylamines in high yield with high recyclability of the polymeric catalyst beads. Very little palladium leached from the polymeric catalyst under the water‐based reaction conditions to provide a green and clean (metal‐uncontaminated) protocol for the preparation of triarylamines, including the optoelectronically active N,N,N′,N′‐tetraaryl‐1,1′‐biphenyl‐4,4′‐diamines (TPDs).     

Design of Bowl‐Shaped N‐Hydroxyimide Derivatives as New Organoradical Catalysts for Site‐Selective C(sp3)−H Bond Functionalization Reactions

A series of new bowl‐shaped N‐hydroxyimide derivatives has been designed and used as selective organoradical catalysts. A number of these bowl‐shaped N‐hydroxyimide derivatives exhibit excellent site‐selectivity in the amination of benzylic C(sp³)?H bonds in aromatic hydrocarbon substrates.     

Copper‐Catalyzed α‐Amination of Phosphonates and Phosphine Oxides: A Direct Approach to α‐Amino Phosphonic Acids and Derivatives

A direct approach to important α‐amino phosphonic acids and its derivatives has been developed by using copper‐catalyzed electrophilic amination of α‐phosphonate zincates with O‐acyl hydroxylamines. This amination provides the first example of C? N bond formation which directly introduces acyclic and cyclic amines to the α‐position of phosphonates in one step. The reaction is readily promoted at room temperature with as little as 0.5 mol % of catalyst, and demonstrates high efficiency on a broad substrate scope.     

固相合成甲胺基阿维菌素苯甲酸盐

To implement the solid phase synthesis of 4““-epi-methylamino-4““-deoxyavermecfin B1 benzoate, tert-butyldimethylsilylchloride was chosen for the first solution synthesis. Then a novel silyl chloride resin 1, achieved from hydroxymethyl polystyrene resin and dimethyldichlorosilane, was used successfully for the attachment of avermectin B1 2. Through oxidation, amination formation, cleavage, and benzoate formation, resin bounded avermectin B1 9 gave 4““-epi-methylamino-4““-deoxyavermectin B1 benzoate 3.     

Studies on the Synthesis and Bioactivities of 4‐Amino Derivatives of Tetramic Acid

In order to study the potential bioactivities of 4‐amino tetramic acid derivatives, the 4‐amination products of pyrrolidine‐2,4‐diones ( 5 ) and 4‐hydroxy‐2‐oxo‐2,5‐dihydro‐1H‐pyrrole‐3‐carboxylates ( 4 ) were prepared. The 4‐amination of 5 took place in high yield when catalyzed by acetic acid, whereas the 4‐amination of 4 was achieved through a 4‐ethoxy intermediate, which was prepared by acidic etherification. Their herbicidal, fungicidal, insecticidal, and antitumor activities were tested. The bioassays showed that two of the compounds exhibited good herbicidal activity against dicot Arabidopsis thaliana at a concentration of 10 µg/mL, and one compound gave instinct fungicidal activity against Pythium sp. at a concentration of 2 µg/mL.     

Simple palladium‐catalyzed C–N bond formation for poor nucleophilicity of aminonaphthalenes

Aromatic amines is not used commonly in allylic amination, presumably because of their less nucleophilic nature compared with the more extensively used benzylamine or relatively stable anionic nitrogen nucleophiles. An eco‐friendly method for C–O bond activation of allylic acetates using palladium associated with ligands in water leading to N‐allylation was described in this study. The palladium‐catalyzed allylic amination of allylic acetate with aminonaphthalenes gave 34–95% yields to the corresponding N‐allylic aminonaphthalenes. Copyright © 2011 John Wiley & Sons, Ltd.