Primary amine, thiourea-based dual catalysis motif for synthesis of stereogenic, all-carbon quaternary center-containing cycloalkanones

The enantioselective synthesis of α,α-disubstituted cycloalkanones has been developed using a primary amine, thiourea-based dual catalysis pathway. A range of electrophiles and ring sizes are tolerated under the reaction conditions. A possible catalytic cycle is presented to explain the reactivity.     

A New and Convenient Synthesis of Amino‐phthalimide (1H‐Isoindole‐1,3(2H)‐dione) Derivatives and Their Photoluminescent Properties

A new and convenient synthesis for amino‐phthalimide (1H‐isoindole‐1,3(2H)‐dione) derivatives has been developed starting from an α,β‐unsaturated ketone. The ketones were reacted with amines to give aromatic amine products. This is the first time that substituted amine groups have been incorporated in aromatic rings. The mechanism of the product formation is rationalized by the 1,2‐addition of amines to ketones. All aromatic compounds exhibited high fluorescence properties at the blue‐green region.     

Photocatalytic α-Tertiary Amine Synthesis via C−H Alkylation of Unmasked Primary Amines

A practical, catalytic entry to α,α,α-trisubstituted (α-tertiary) primary amines by C−H functionalisation has long been recognised as a critical gap in the synthetic toolbox. We report a simple and scalable solution to this problem that does not require any in situ protection of the amino group and proceeds with 100 % atom-economy. Our strategy, which uses an organic photocatalyst in combination with azide ion as a hydrogen atom transfer (HAT) catalyst, provides a direct synthesis of α-tertiary amines, or their corresponding γ-lactams. We anticipate that this methodology will inspire new retrosynthetic disconnections for substituted amine derivatives in organic synthesis, and particularly for challenging α-tertiary primary amines.     

Chiral Primary Amine Catalyzed α-Arylation of Simple Ketones via Asymmetric Retro-Claisen Cleavage

Highly enantioselective α-arylation of simple ketones has been achieved by chiral primary amine catalyzed asymmetric retro-Claisen cleavage of β-diketones. This mild organocatalytic strategy enables the construction of α-aryl tertiary carbon stereocenters in good yields and excellent enantioselectivities (up to 98 % ee) with the para-quinone monoimines as aryl sources. Furthermore, oxidative catalytic asymmetric α-arylation has also been realized with free p-aminophenols.     

Synthesis of a new 1,4-dihydropyridine containing the imidazo[1,5-α]pyridine nucleus

The synthesis of the new dihydropyridine diethyl 1,4-dihydro-4-(imidazo[1,5-α]pyridin-8-yl)-2,6-dimethyl-pyridine-3,5-dicarboxylate ( 1 ) is described. After many attempts to prepare the key intermediate aldehyde 2a by different approaches, this compound has been obtained in good yields from methyl 2-cyano-3-pyridinecar-boxylate ( 10 ). A three-step procedure involving reduction to the amine, formylation with concomitant cyclization and reduction of the ester group was used.     

Enamines—XXXIX : Enamines from cyclopropylketones

The enamines from cyclopropyl-methyl-, -ethyl- and -cyclopentylketone have been prepared by reaction of the ketone with a secondary amine and TiCl₄. Their vinylcyclopropane structure has been demonstrated by NMR. The reaction of dicyclopropylketone, cyclopropylphenylketone or cyclopropyl-α-thienylketone with secondary amines and TiCl₄ afforded homoallylic rearrangement products, namely 1-cyclopropyl-, 1-phenyl- and 1-(α-thienyl)-1,4-diamino-1-butene, respectively.     

‘Bis-ornithine’ (2,2-bis(aminopropyl)glycine): a new tetravalent template for assembling different functional peptides

Synthesis of bis-ornithine, a new C^α,α-disubstituted α-amino acid bearing orthogonally protected α and δ amine groups is reported. Bis-ornithine (bisOrn) and dipeptides containing bis-ornithine have been synthesized in solution up to multigram scale. As a first example, one of these compounds Boc-βAla-bisOrn(Alloc)₂-OH has been attached to a solid support and used as template for the synthesis of a symmetrical assemblage of peptides.     

Ni‐Catalyzed Asymmetric Cycloisomerization of Dienes by Using TADDOL Phosphoramidites

A library of α,α,α,α‐tetraaryl‐1,3‐dioxolane‐4,5‐dimethanol (TADDOL)‐based phosphoramidites has been synthesized and applied in the Ni‐catalyzed cycloisomerization of different dienes. Through the systematic variation of the three structural motifs of the lead structure, that is, the amine moiety, the protecting group, and the aryl substituents, the ligand features could be optimized for the asymmetric cycloisomerization of the model substrate diethyl diallylmalonate. The substrate scope of the new catalytic system was extended to other diallylic substrates, including unsymmetrical dienes. Overall remarkably high activities of up to approximately 13 500 h^?1, very high selectivities toward five‐membered exo‐methylenecyclopentanes, and enantioselectivities of up to 92 % ee have been achieved.     

Scalable Cu(Ⅱ)-mediated intramolecular dehydrogenative phenol-phenol coupling:Concise synthesis of enantiopure axially chiral homo-and hetero-diphenols

An intramolecular dehydrogenative homo-and hetero-coupling of phenols has been successfully developed for quick preparation of enantiopure axial diphenols under mild Cu(Ⅱ)-mediated conditions,using((4 S,5 S)-2,2-dimethyl-1,3-dioxolane-4,5-diyl)dimethanol as the chiral auxiliary.The commercially available(R)-α-met hylbenzy la mine was identified as the best amine ligand for Cu(Ⅱ) in the reactions.A variety of homo/hetero bis-dihydroxylbenzoate substrates were examined,affording the corresponding axially chiral diphenols with satis factory to excellent diastereomeric ratios,and a representative scalable preparation was also attempted.A formal synthesis of natural product(+)-deoxyschizandrin has been achieved in this work using one axially chiral diphenol as the synthetic intermediate.     

Asymmetrical nonbridgehead nitrogen—XXIII: Chiral 3,3-bis(trifluoromethyl)diaziridines

By means of the reaction of O-tosyloxime 1a with propargyl amine, esters of glycine and (S)-α-alanine, β-acetoxyethyl amine and β-dimethylaminoethyl amine functionally substituted 3,3-bis(trifluoromethyl)diaziridines 2a–g have been obtained. In the reactions with more bulky amines, (S)-phenylalanine Et ester, (R, S)-α-phenylethyl amine and t-butyl amine, 1a acts as a tosylating reagent. The ester group in diaziridine 2e is readily saponified by alcoholic alkali, whereas diaziridine 2c is rearranged in these conditions with ring-expansion. Complete asymmetric transformation has been found to take place on the formation of the solid phase of diastereomers 2d and 2j, and a closed cycle of diastereomeric transformations has been accomplished. Diaziridine 2g with chiral centres only at the nitrogen atoms has been obtained with the optical purity of 85.5% by resolution via salt 5c with d-(+)-camphor-3-carboxylic acid. The absolute configuration of (+)-2g and its quaternary salt, (+)-2h, has been determined from CD spectra. Optically active (?)-2h salt (optical purity 2.0%) has been also obtained by asymmetric synthesis on the basis of 1–10-camphorsulphonyl oxime 1b. From the kinetics of 2g, h racemization and 2d, e, i, j, k epimerization the energy parameters of the inversion of N atoms in 3,3-bis (trifluoromethyl)diaziridines have been determined.     

L-α-三氟乙酰基氧基丙酰基氯对外消旋胺及氨基酸的气相色谱拆分

L-乳酸与三氟乙酸酐反应, 生成L-α-三氟乙酰氧基乳酸, 再与二氯亚砜作用, 合成新的手性试剂----L-α-三氟乙酰氧基丙酰氯. 它与DL-α-苯乙胺及三种DL-α-氨基酸反应, 生成相应的非对映异构体酰胺, 在以Carbowax为固定相的毛细管柱上进行气相色谱拆分. 以相应的L-胺及L-氨基酸在相同条件下进行比较, 发现D-异构体的保留时间较短 .     

Quaternary ammonium polymers from 1,4-diaza[2.2.2]bicyclooctane

Menschutkin reactions of 1,4-diaza[2.2.2]bicyclooctane with various α,α-dibromoalkanes and α,α′-dibromoxylenes have been studied in two solvent systems and at different temperatures. It was found that quaternary ammonium polymers could easily be prepared from this rigid, bicyclic, ditertiary amine.     

Beyond the chiral pool: a general approach to β-amino-α-keto amides

A simple route was developed for the synthesis of optically enriched β-amino-α-keto amides. The highly diastereoselective addition of alkyl dithiolanecarboxylates to optically enriched sulfinimines affords the corresponding β-amino-α-keto esters in which the ketone carbonyl group is protected as a dithiolane. Amidation of the ester functionality with a primary amine proceeds readily at room temperature. Treatment with HCl cleaves the N-S bond of the sulfinyl group to provide a free amine functionality, which can then be incorporated into a peptide. Removal of the dithiolane protecting group under oxidative conditions proceeds without epimerization as exemplified by a model dipeptide.     

Total synthesis of (±)-α,γ-onoceradienedione and lansic acid

Unsymmetrical onoceranoid triterpenes,α,γ-onoceradienedione and lansic acid, have been synthesized effectively by means of mercury(II) triflate/amine complex-induced olefin cyclization.     

An amine-catalyzed enantioselective [3+2] cycloaddition of azomethine ylides and α,β-unsaturated aldehydes: applications and mechanistic implications

The catalytic enantioselective [3+2] cycloaddition between azomethine ylides and α,β-unsaturated aldehydes catalyzed by α,α-diphenylprolinol has been studied in detail. In particular, the reaction has been extended to the use of 2-alkenylidene aminomalonates generated in situ as azomethine ylide precursors. These reactions lead to the formation of pyrrolidines containing a 5-alkenyl side chain with potential for chemical manipulation. Moreover, a detailed and concise computational study has been carried out to understand the exact nature of the mechanism of this reaction and especially the consequences derived from the incorporation of the chiral secondary amine catalyst on the reaction pathway.     

High-yielding synthesis of 2-arylacrylamides via homogeneous catalytic aminocarbonylation of α-iodostyrene and α,α′-diiodo-1,4-divinylbenzene

Highly reactive iodoalkenes (α-iodostyrene and α,α′-diiodo-1,4-divinylbenzene) were prepared and used as substrates in palladium-catalysed aminocarbonylation reaction. Regardless of the type of amine nucleophile the corresponding N-substituted phenylacrylamides have been formed chemoselectively in nearly quantitative yields. High isolated yields (up to 83%) have been achieved both with unfunctionalised simple amines and amino acid methyl esters under mild reaction conditions.     

Investigating the reaction mechanism and organocatalytic synthesis of α,α'-dihydroxy ketones

A biomimetic TK one-pot reaction using hydroxypyruvate and aldehydes to generate α,α'-dihydroxy ketones in water has recently been described. To investigate this tertiary-amine mediated reaction mechanism two approaches were used. Firstly, (13)C labelled lithium hydroxypyruvate was synthesised and used to establish where hydroxypyruvate is incorporated in the product. In separate experiments reaction intermediates were also successfully intercepted and structurally identified using ESI-MS with tandem mass spectrometry ESI-MS/MS. These studies indicated that two mechanisms appear to be operating, one involving the addition of the tertiary amine catalyst to hydroxypyruvate, the other an aldol-based mechanism. Since the first mechanism may enable facial stereodifferentiation in the addition of intermediates to the aldehyde, a preliminary study on the use of chiral catalysts was performed and the first asymmetric organocatalytic synthesis of α,α'-dihydroxy ketones in aqueous media achieved, in up to 50% ee, using a quinine ether catalyst.     

Photocatalytic α‐Tertiary Amine Synthesis via C−H Alkylation of Unmasked Primary Amines

A practical, catalytic entry to α,α,α‐trisubstituted (α‐tertiary) primary amines by C?H functionalisation has long been recognised as a critical gap in the synthetic toolbox. We report a simple and scalable solution to this problem that does not require any in situ protection of the amino group and proceeds with 100 % atom‐economy. Our strategy, which uses an organic photocatalyst in combination with azide ion as a hydrogen atom transfer (HAT) catalyst, provides a direct synthesis of α‐tertiary amines, or their corresponding γ‐lactams. We anticipate that this methodology will inspire new retrosynthetic disconnections for substituted amine derivatives in organic synthesis, and particularly for challenging α‐tertiary primary amines.     

磁性碱木素胺稳定的Ru纳米粒子催化α-蒎烯加氢反应

通过Mannich反应在碱木素结构中引入胺源,再结合共沉淀法制备了包裹Fe₃O₄磁核的稳定金属粒子的碱木素胺载体,并进一步构建了催化可再生资源α-蒎烯加氢反应的Ru纳米粒子催化剂.通过元素分析、粉末X射线衍射、傅里叶变换红外光谱、电感耦合等离子体原子发射光谱、透射电子显微镜、热重分析和X射线光电子能谱等方法对该催化剂进行表征.结果表明,碱木素中的苯环和含氧基团均对金属粒子有稳定作用,但胺源的引入可更加有效地稳定金属粒子.经过对催化剂制备工艺、木质素类型、胺源类型和胺源含量的筛选,得到活性最优的催化剂Fe₃O₄@0.8ALN₁-Ru,Ru负载量为1.92 mmol/g,Ru粒子粒径为（2.1±0.5）nm.该催化剂在n（α-蒎烯）/n（Ru）=65.8,1 MPa H₂条件下70℃催化1 mL α-蒎烯加氢反应2 h,可获得99.64%的α-蒎烯转化率和96.52%的顺式蒎烷选择性,并表现出良好的重复使用稳定性.     

NHC-catalysed retro-aldol/aldol cascade reaction enabling solvent-controlled stereodivergent synthesis of spirooxindoles

An N-heterocyclic carbene (NHC)-catalysed retro-aldol/aldol cascade reaction of spirooxindole-based β-hydroxyaldehyde has been developed. The ring opening-closure process enables the diastereodivergent synthesis of spirocyclopentaneoxindole products with four consecutive stereocenters by simply changing the reaction solvents (THF or DCE). The Michael/aldol/retro-aldol/aldol sequential protocol allows the diastereodivergent synthesis of spirocyclopentaneoxindoles from 3-substituted oxindole and α,β-unsaturated aldehyde under the relay catalysis of a chiral secondary amine and an NHC catalyst. Moreover, four stereoisomers of the product can be selectively provided by using different combinations of a chiral secondary amine and a solvent.