Synthesis of α-trifluoromethyl-phenethylamines from α-trifluoromethyl β-aryl enamines and β-chloro-β-(trifluoromethyl)styrenes

A novel synthetic approach towards α-trifluoromethyl-phenethylamines was elaborated by reduction of the electron deficient β-aryl-α-trifluoromethyl enamines and imines with sodium cyanoborohydride in the presence of trifluoroacetic acid. The starting imines were prepared by the reaction of primary amines with β-aryl-α-trifluoromethyl enamines or β-chloro-β-(trifluoromethyl)styrenes.     

基于苯并硫氮杂卓的亚胺、烯胺在质子溶剂中的稳定性及其互变异构

用核磁共振法研究了亚胺型杂卓1和烯胺型杂卓2在不同质子溶剂—甲醇、乙醇、叔丁醇、乙酸及CF3CO2D的DMSO-d6溶液中的稳定性及互变异构.结果表明,烯胺型杂卓2在上述溶剂中稳定,亚胺型杂卓1在酸性较弱的质子溶剂中(乙醇、叔丁醇)及较低的温度下(≤30℃)基本稳定,在酸性较强的质子溶剂中(甲醇、乙酸、CF3CO2D的DMSO-d6溶液)向烯胺转化,而且随着溶剂酸性的增强、温度的升高以及反应物与溶剂接触时间的延长,亚胺向烯胺的转化进一步加强.本文还以1a和1b为例,研究了在乙酸溶液中亚胺型杂卓向烯胺型杂卓转化的热力学和动力学特征.研究表明,在283~333 K范围内,该转化的焓变(△H)和熵变(△S)均大于零,吉布斯自由能变(△G)小于零,因此其是吸热、自发及熵增加的过程,该过程可用二级动力学方程来描述,质子对亚胺向烯胺的转化起催化作用.     

Regioselectivity of enamine reactions,preferential 2,2-disubstitution of 2-methylcyclohexanone imines

Secondary enamines derived from imines of unsymmetrical α-substituted ketones react with electrophilic alkenes at the more substituted position to give α,α-disubstituted ketones on hydrolysis.     

(Dynamic) Kinetic Resolution of Enamines/Imines: Enantioselective N‐Heterocyclic Carbene Catalyzed [3+3] Annulation of Bromoenals and Enamines/Imines

The enantioselective N‐heterocyclic carbene catalyzed [3+3] annulation of α‐bromoenals by dynamic kinetic resolution (DKR) of enamines and normal resolution of α,α‐disubstituted imines were developed. The corresponding substituted dihydropyridones were isolated in good yields with excellent diastereo‐ and enantioselectivities, and a high selective factor (up to 83) was realized for the resolution of α,α‐disubstituted imines.     

金属催化端炔与亚胺衍生物亲核加成制备炔丙基胺的研究进展

综述了端炔与C=N双键亲核加成制备炔丙基胺的合成方法的研究进展.其中包括醛亚胺的间接或直接偶联反应,烯胺的间接偶联反应,酮亚胺的间接或直接偶联反应等.参考文献30篇.     

Chemo- and regioselectivity in the reactions between highly electrophilic fluorine containing dicarbonyl compounds and amines. Improved synthesis of the corresponding imines/enamines

Chemo- and regioselectivity in the reactions between highly electrophilic fluorine containing dicarbonyl compounds (ethyl 4,4,4-trifluoroacetoacetate, 3,3,3-trifluoropyruvate and 1,1,1,5,5,5-hexafluoropentane-2,4-dione) and various benzylamines were systematically studied. The results obtained lead to the development of a generalized and practical method for large-scale synthesis of the corresponding imines/enamines, useful starting materials for preparation fluorinated amines and amino acid.     

Palladium catalyzed amination of vinyl chlorides: a new entry to imines, enamines and 2-amino-1,3-butadienes

Vinyl chlorides are employed for the first time in palladium catalyzed cross-coupling reactions with amines to furnish imines and enamines. The new methodology has been applied to the synthesis of 2-amino-1,3-butadienes, that could not be achieved from the corresponding bromides.     

Relative Stability of the Key Enamine,Oxazolidinone, and Imine Intermediates in Some Proline-catalyzed Asymmetric Reactions

Many proline-catalyzed asymmetric addition reactions with ketones as substrates were assumed to involve a key intermediate, an enamine, produced by the condensation of proline and ketone. In this paper, the key intermediate enamines derived from L-proline and cyclohexanone （or acetone） as well as the corresponding oxazolidinone and imine tautomers have been investigated by means of density functional calculations at the B3LYP/6-311＋G^＊＊ level. The predicted order of stability for these tautomers is oxazolidinones 〉 enamines 〉 imines in gas phase and oxazolidinones 〉 imines 〉 enamines in aprotic THF solvent. This prediction explains why enamine intermediate can not be observed experimentally. The predicted energy/enthalpy difference between the formal oxazolidinone structure and the zwitterionic imine structures is very small in THF solvent, suggesting the oxazolidinone-to-imine tautomerization can be readily induced in solvent. ^13C NMR chemical shifts of the oxazolidinone and imine structures have been computed and used to explain the experimental NMR spectra observed in oxazolidinone-to-imine tautomerization induced by protic solvent.     

Highly enantioselective Mannich reactions with α-aryl silyl ketene acetals and imines

Mannich reactions with chiral silicon Lewis acid activated acylhydrazones and α-aryl silyl ketene acetals and α-aryl,α-alkyl silyl ketene imines proceed efficiently and with good to excellent levels of both diastereoselectivity and enantioselectivity. The reactions provide access to α-aryl,β-hydrazido esters and α-aryl,α-alkyl,β-hydrazido nitriles, which are valuable analogs of β-amino acids.     

Phosphine-Catalyzed [4+1] Cycloadditions of Allenes with Methyl Ketimines,Enamines, and a Primary Amine

Unprecedented phosphine-catalyzed [4+1] cycloadditions of allenyl imides have been discovered using various N-based substrates including methyl ketimines, enamines, and a primary amine. These transformations provide a one-pot access to cyclopentenoyl enamines and imines, or (chiral) γ-lactams through two geminal C−C bond or two C−N bond formations, respectively. Several P-based key intermediates including a 1,4-(bis)electrophilic α,β-unsaturated ketenyl phosphonium species have been detected by ³¹P NMR and HRMS analyses, which shed light on the postulated catalytic cycle. The synthetic utility of this new chemistry has been demonstrated through a gram-scaling up of the catalytic reaction as well as regioselective hydrogenation and double condensation to form cyclopentanoyl enamines and fused pyrazole building blocks, respectively.     

Reversal of diastereoselectivity in reactions of the trifluoroacetaldehyde ethyl hemiacetal with enamines and imines: metal-free, complementary anti- and syn-selective synthesis of 4,4,4-trifluoro-1-aryl-3-hydroxy-2-methyl-1-butanones

A complete reversal of diastereoselectivity was observed for reactions of the trifluoroacetaldehyde ethyl hemiacetal with enamines and imines, derived from propiophenones, that produce 4,4,4-trifluoro-1-aryl-3-hydroxy-2-methyl-1-butanones. This process serves as the first reliable, metal-free, complementary anti- and syn-selective method to prepare 4,4,4-trifluoro-1-aryl-3-hydroxy-2-methyl-1-butanones.     

Mg-promoted double silylation of trifluoroacetimidoyl chlorides. A new entry to the fluorinated dianion equivalents

[reaction: see text] A Mg(0)/Me(3)SiCl system was found to be effective for the preparation of a novel fluorinated dianion equivalent. A one-pot reaction sequence involving reductive C-F and C-Cl bond cleavage reactions of trifluoroacetimidoyl chlorides afforded bis-silylated difluoroenamines. Subsequent carbon-carbon bond-forming reactions of the bis(silyl)enamines with two kinds of electrophiles gave a variety of difluorinated imines.     

Phosphine‐Catalyzed [4+1] Cycloadditions of Allenes with Methyl Ketimines,Enamines, and a Primary Amine

Unprecedented phosphine‐catalyzed [4+1] cycloadditions of allenyl imides have been discovered using various N‐based substrates including methyl ketimines, enamines, and a primary amine. These transformations provide a one‐pot access to cyclopentenoyl enamines and imines, or (chiral) γ‐lactams through two geminal C?C bond or two C?N bond formations, respectively. Several P‐based key intermediates including a 1,4‐(bis)electrophilic α,β‐unsaturated ketenyl phosphonium species have been detected by ³¹P NMR and HRMS analyses, which shed light on the postulated catalytic cycle. The synthetic utility of this new chemistry has been demonstrated through a gram‐scaling up of the catalytic reaction as well as regioselective hydrogenation and double condensation to form cyclopentanoyl enamines and fused pyrazole building blocks, respectively.     

Palladium-catalyzed cross-coupling reactions of amines with alkenyl bromides: a new method for the synthesis of enamines and imines

The palladium-catalyzed cross-coupling reaction of alkenyl bromides with secondary and primary amines gives rise to enamines and imines, respectively. This new transformation expands the applicability of palladium-catalyzed C-N bond forming reactions (the Buchwald-Hartwig amination), which have mostly been applied to aryl halides. After screening of different ligands, bases, and solvents, the catalytic combination [Pd(2)(dba)(3)]/BINAP in the presence of NaOtBu in toluene gave the best results in the cross-coupling of secondary amines with 1-bromostyrene (dba=dibenzylideneacetone, BINAP=2,2'-bis(diphenylphosphino)-1,1'-binaphthyl). The corresponding enamines are obtained cleanly and in nearly quantitative yields. However, steric hindrance seems to be a limitation of the reaction, as amines carrying large substituents are not well converted. The same methodology can be applied to the coupling of secondary amines with 2-bromostyrene. Moreover, the reaction with substituted 2-bromopropenes allows regioselective synthesis of isomerizable terminal enamines without isomerization of the double bond. The best catalytic conditions for the cross-coupling of 1-bromostyrene with primary amines include again the use of the Pd(0)/BINAP/NaOtBu system. The reaction gives rise to the expected imines in very short times and with low catalyst loadings. A set of structurally diverse imines can be prepared by this methodology through variations in the structure of both coupling partners. However, 2-bromostyrene failed to give good results in this coupling reaction, probably due to product inhibition of the catalytic cycle. Competition experiments of vinyl versus aryl amination reveal that the reaction occurs preferentially on vinyl bromides.     

Catalytic, asymmetric synthesis of α-phenoxy-β-aryl-β-lactams

The reactions of phenoxyacetyl chloride with aryl imines in the presence of catalytic quantities of a silyl cinchona alkaloid and an achiral Lewis acid affords α-phenoxy-β-aryl-β-lactams. These reactions presumably proceed by way of ketene or acyl ammonium enolate intermediates. These reactions occur in a high enantioselectivity regardless of the nature of the Lewis acid, however, a high diastereoselectivity depended on the use of a hindered lanthanide complex as the Lewis acidic co-catalyst.     

Asymmetric Conjugate Addition of Malonate Esters to α,β‐Unsaturated N‐Sulfonyl Imines: An Expeditious Route to Chiral δ‐Aminoesters and Piperidones

The asymmetric conjugate addition of malonate esters to α,β‐unsaturated N‐sulfonyl imines is catalyzed by PyBOX/La(OTf)₃ complexes in the presence of 4 Å MS. The reaction gives the corresponding E enamines bearing a stereogenic center at the allylic position with good yields and enantiomeric ratios up to 97:3. This reaction provides a synthetic entry to chiral δ‐aminoesters and piperidones.     

Pyridazines. LXX. Reactions of azidoazolopyridazines with unsaturated compounds

Cycloaddition reactions of azidoazolopyridazines with unsaturated esters, cyclic enol ethers, styrene, 2-vinyl-pyridine, bicyclo[2.2.1]heptene, dicyclopentadiene and dehydrobenzene were investigated. The reaction proceed via the intermediate Δ² -1,2,3-triazolines which were in most cases termolabile and decomposed further to give the final products which were enamines, imines of fused aziridines.     

An enantioselective Brønsted acid catalyzed enamine Mannich reaction

An enantioselective Br?nsted acid catalyzed Mannich reaction between acetophenone derived enamines and N-Boc imines has been developed. Simple diol (S)-H(8)-BINOL has been identified as the optimal catalyst, to afford versatile beta-amino aryl ketones in good yield and enantiomeric excess.     

Stereoselective α,α'-annelation reactions of 1,3-dioxan-5-ones

Pyrrolidine enamines derived from three 1,3-dioxan-5-ones undergo α,α'-annelation reactions with methyl α-(bromomethyl)acrylate to produce bridged 2,4-dioxabicyclo[3.3.1]nonane ring systems with complete stereocontrol. Stereochemical outcomes have been rationalized based on steric and stereoelectronic interactions in intermediate boat-like conformations of the 1,3-dioxane ring and subsequent kinetic protonation to set an axial ester group on the cyclohexanone ring. Base-mediated ester epimerization provides the stereochemical array found in the highly oxygenated cyclohexane ring of phyllaemblic acid and glochicoccins B and D.     

Imines et enamines stanniques : IV. Protolyse: synthese d'enamines secondaires; structure,isomerisation, reactivite vis a vis de l'acrylonitrile

The partial protolysis of organotin imines—enamines leads to organic secondary enamines, which we found to be stable in completely aprotic media.Their structure was determined by IR and NMR methods, and their reactivity towards acrylonitrile studied. The results show a much greater reactivity for enamines, as compared to that of the corresponding imine tautomers.