One-Pot Synthesis of Chiral N-Arylamines by Combining Biocatalytic Aminations with Buchwald–Hartwig N-Arylation

The combination of biocatalysis and chemo-catalysis increasingly offers chemists access to more diverse chemical architectures. Here, we describe the combination of a toolbox of chiral-amine-producing biocatalysts with a Buchwald–Hartwig cross-coupling reaction, affording a variety of α-chiral aniline derivatives. The use of a surfactant allowed reactions to be performed sequentially in the same flask, preventing the palladium catalyst from being inhibited by the high concentrations of ammonia, salts, or buffers present in the aqueous media in most cases. The methodology was further extended by combining with a dual-enzyme biocatalytic hydrogen-borrowing cascade in one pot to allow for the conversion of a racemic alcohol to a chiral aniline.     

Organocatalytic asymmetric fulvene formation

The first catalytic asymmetric formation of a fulvene from a racemic α,α-disubstituted aldehyde has been developed. Dynamic kinetic resolution of rac-2-phenylpropanal by a simple, modularly designed supramolecular organocatalyst consisting of inexpensive components has been established, producing the desired fulvene in good yields and moderate enantioselectivities. Herein we propose a mechanistic interpretation of the observed solvent- and additive-induced stereoselectivity reversal.     

Reactions of 5,6,7,8-tetrafluoro-4-hydroxycoumarin derivatives with benzylamine and aniline

5,6,7,8-Tetrafluoro-4-hydroxycoumarin reacted with benzylamine under mild conditions to give a stable salt, while its refluxing with aniline or benzylamine in xylene afforded 5,6,7,8-tetrafluoro-4-phenyl(benzyl)aminocoumarins. Reactions of 3-acetyl(acetimidoyl)-5,6,7,8-tetrafluoro-4-hydroxycoumarins with benzylamine followed different pathways, depending on the solvent. Condensation at the acyl substituent can be accompanied by replacement of the F atom in position 7. 3-Acetylcoumarin formed a salt, while 3-acetimidoylcoumarin yielded a 7-monosubstituted product. 3-Acetyl(acetimidoyl)-5,6,7,8-tetrafluoro-4-hydroxycoumarins reacted with aniline to give only 5,6,7,8-tetrafluoro-4-hydroxy-3-(N-phenylacetimidoyl)coumarin. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1170–1174, July, 2006.     

Micellar electrokinetic biofluid analysis of biogenic amines using on-line sample concentration and UV laser-induced native fluorescence detection

A simple and sensitive sweeping micellar electrokinetic chromatography method coupled with UV laser-induced native fluorescence detection has been developed for quantitative analysis of biogenic amines in biofluids. The background electrolyte comprised 30 mmol L⁻¹ phosphoric acid and 20 mmol L⁻¹ sodium dodecyl sulfate. The concentration limits of detection of analytes using sweeping-micellar electrokinetic chromatography (sweeping-MEKC) were in the range 7–100 nmol L⁻¹, which were 250–3600-fold improvement for dopamine, DOPA and epinephrine compared with conventional capillary zone electrophoresis. An improvement of approximately 20-fold was observed for all analytes compared with typical micellar electrokinetic chromatography conditions. Baseline separation was achieved for the all analytes within 12 min and migration-time and peak-area repeatability were better than RSD 0.35% and 5.68%, respectively. The developed method was applied to measure the biogenic amines in biofluids extracted from wheat phloem sap, human plasma and human urine.     

Preparation of monodispersed vinylpyridine–divinylbenzene porous copolymer resins and their application to high-performance liquid chromatographic separation of aromatic amines

For the separation of aromatic amines, two types of monodispersed porous polymer resins were prepared by the copolymerization of 2-vinylpyridine and 4-vinylpyridine with divinylbenzene in the presence of template silica gel particles (particle size 5 μm), followed by dissolution of the template silica gel in an alkaline solution. The transmission electron micrographs and the scanning electron micrograph revealed that these templated polymer resins have a spherical morphology with a good monodispersity and porous structure. Using these monodispersed polymer resins, the high-performance liquid chromatographic separation of aromatic amines in the mobile phases of pHs 2.0, 2.9, 4.1, 7.2 and 11.7 were carried out. The 2-vinylpyridine–divinylbenzene copolymer resins showed slightly stronger retentions for aromatic amines than the 4-vinylpyridine–divinylbenzene copolymer resins. Under acidic conditions (around pH 2.0), aniline and the toluidines showed no retention on these copolymer resins due to the repulsion between the cationic forms of these amines and pyridinium cations in the stationary phase, whereas less basic aromatic amines or non-basic acetanilide showed slight retentions. Above pH 4.1, the separation of aromatic amines with these polymer resins showed a typical reversed-phase mode separation. Therefore, the separation patterns of aromatic amines are effectively tunable by changing the pH value of the mobile phases. A good separation of eight aromatic amines was achieved at pH 2.9 using the 2-vinylpyridine–divinylbenzene copolymer resins.     

Separation and identification of aliphatic amine derivatives with a new fluorescent reagent using high-performance liquid chromatography and thin-layer chromatography

Summary The use of 1,2-naphthoylenebenzimidazole-6-sulphochloride has been proposed as the reagent for derivatization of aliphatic amines prior to their separation, identification and quantitation both in HPLC and in TLC. The reaction of amines with this compound is quantitative and highly fluorescent derivatives are formed that provide favourable detection limits and sensitivity as compared to Dansyl derivatives of aliphatic amines. Actual detection limits achieved correspond to ca. 10^–10 mol of the amine in a spot after elution from the thin-layer plate and to ca. 5·10^–14 mol of the amine in a sample volume of 10 l injected into the liquid chromatograph. The use of this derivatization reagent offers good potential for the analysis of trace amounts of amines in environmental samples and in biological material.Presented at the 14th International Symposium on Chromatography London, September, 1982     

Efficient copper(II)-catalyzed transamidation of non-activated primary carboxamides and ureas with amines

Amid(e) them all: primary carboxamides and ureas react with aromatic and aliphatic amines in the presence of a copper catalyst to give a wide range of functionalized amides.     

Interaction of Methyl 5,6-Dialkyl-2-amino-3-cyanopyridine-4-carboxylates with Primary Amines

An unusual direction has been found for the interaction of alkyl 5,6-dialkyl-2-amino-3-cyanopyridine-4-carboxylates with primary amines leading to the formation of 2,6,7-trialkyl-4-amino-2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-1,3-diones.     

Aldehyde cruciforms: dosimeters for primary and secondary amines

We demonstrate that aldehyde-substituted donor-acceptor cruciforms [1,4-bis(arylethynyl)-2,5-distyrylbenzenes] are useful dosimeters for primary amines, primary diamines, and secondary amines. The 1,n-diamines are particularly reactive towards this dosimeter and can be detected in less than 100 ppm concentration. Using a single aldehyde-functionalized cruciform in seven different solvents allowed us to discern fourteen different amines by digital photography and statistical evaluation of the response patterns extracted as red, green, blue (RGB) values.     

Lanthanide‐Catalyzed Reversible Alkynyl Exchange by Carbon–Carbon Single‐Bond Cleavage Assisted by a Secondary Amino Group

Lanthanide‐catalyzed alkynyl exchange through C?C single‐bond cleavage assisted by a secondary amino group is reported. A lanthanide amido complex is proposed as a key intermediate, which undergoes unprecedented reversible β‐alkynyl elimination followed by alkynyl exchange and imine reinsertion. The in situ homo‐ and cross‐dimerization of the liberated alkyne can serve as an additional driving force to shift the metathesis equilibrium to completion. This reaction is formally complementary to conventional alkyne metathesis and allows the selective transformation of internal propargylamines into those bearing different substituents on the alkyne terminus in moderate to excellent yields under operationally simple reaction conditions.