ABSTRACT
A strategy for the ß-sp3 functionalisation of cyclic amines is described. Regioselective conversion of protected amines to enecarbamates is achieved through electrochemical oxidation; these intermediates can be derivatised by functionalised alkyl halides under photoredox catalysis. The potential of the methods is highlighted by direct growth of a DCP2B-binding fragment.
ABSTRACT
A new chemoselective (enzymatic desymmetrization/Ru-catalyzed C-H activation) sequence to obtain differently substituted furans from the largely available 2,5-furandicarboxylic acid (FDCA) was developed. Series of di- and trisubstituted furans were prepared in very good yields and excellent chemoselectivity. This study discloses a new approach towards valorization of the furanics platform through the use of FDCA as a stable intermediate, thus circumventing the chemical instability of the parent 5-hydroxymethylfurfural.
ABSTRACT
A new, irreversible aldehyde conjugation reaction in aqueous media was developed. α-Aminooxy acetohydrazides undergo irreversible condensation reactions with aliphatic, aromatic, or unsaturated aldehydes and isatins in a mixture of acetonitrile and acetate buffer at pH 4 to yield 1,2,4-oxadiazinan-5-one heterocycles in excellent isolated yields (40-99%). This class of heterocycles proved to be hydrolytically stable throughout a wide range of temperatures and pH (4.5-7).
ABSTRACT
The first general protocol for the preparation of symmetric triarylmethanes bearing secondary anilines by ytterbium-catalyzed Friedel-Crafts reaction of hetero(aryl) aldehydes and secondary anilines is reported. Mechanistic studies indicated that the iminium ion intermediate is the electrophilic partner. The reaction is greatly accelerated by high pressure (9 kbar) and showed a broad substrate scope on the hetero(aryl) aldehyde. The new triarylmethanes exhibited activity against HT-29 cancer cell lines, with the best result scoring an IC50 of 1.74 µM.
ABSTRACT
The selective ε-functionalization of 5-substituted furfurals via trienamine intermediates is reported herein. This methodology was successfully applied to several 5-substituted furfurals with different amines via formation of a trienamine through the furan ring. The rationalized reaction mechanism involves the addition of the trienamine intermediate to its corresponding iminium-ion producing new furan-containing scaffolds.
Subject(s)
Amines/chemistry , Furaldehyde/analogs & derivatives , Furans/chemistry , Imines/chemistry , Catalysis , Molecular Structure , StereoisomerismABSTRACT
Folic acid targeting by functionalization of the terminal γ-carboxylic acid is one of the most important strategies to selectively deliver chemotherapeutics and dyes to cancer cells which overexpress folate receptors. However, conjugation of folic acid is limited by its unique solubility and by selectivity issues imposing the need for expensive preparative reverse-phase chromatographic purification to isolate γ-folate conjugates. Herein is provided a novel synthetic tool for the synthesis of new folic acid conjugates with excellent γ-purity based on strain-promoted alkyne-azide cycloadditions with a γ-folate-cyclooctyne conjugate 3. To demonstrate the potential of this methodology several new folate conjugates were synthesized with high γ-purity and without using any type of chromatographic purification by reacting conjugate 3 with several fluorescent probes, polymers and siliceous materials bearing azide. In addition, the cycloaddition reaction between conjugate 3 and an azido-derived fluorescent dye was successfully performed in cellular media leading to an increase of fluorescence in the cells which overexpress folate receptors (NCI-H460).
Subject(s)
Click Chemistry/methods , Folic Acid/chemistry , Chromatography, High Pressure Liquid , Chromatography, Reverse-Phase , Ethanolamine/chemistry , HEK293 Cells , Humans , Microscopy, Confocal , Spectrometry, FluorescenceSubject(s)
Alkenes/chemistry , Imines/chemistry , Ketones/chemistry , Organometallic Compounds/chemistry , Sulfides/chemistry , Alkenes/chemical synthesis , Catalysis , Conservation of Natural Resources , Imines/chemical synthesis , Ketones/chemical synthesis , Stereoisomerism , Sulfides/chemical synthesisABSTRACT
In this paper, we compare and discuss the very different crystal structures and supramolecular arrangements obtained when using different crystallization solvents with the same organometallic moiety. The new title tetrahydrofuran (THF) solvate, [Rh(2)(C(2)H(3)O(2))(4)(C(27)H(36)N(2))(2)] x 4 C(4)H(8)O, is compared with the toluene trisolvate reported previously by us [Góis, Trindade, Veiros, Andre, Duarte, Afonso, Caddick & Cloke (2007). Angew. Chem. Int. Ed. 46, 5750-5753]. The molecular structures of the two complex molecules display a similar conformation, but due to the presence of different solvent molecules, the two solvates crystallize in different space groups and exhibit quite diverse supramolecular assemblies. The toluene solvate crystallizes in the triclinic space group P1, while in the presence of THF, the monoclinic P2(1)/c space group is obtained, with the complex molecule residing on an inversion centre. The resulting crystal packing displays no classical hydrogen bonds but different supramolecular synthons give rise to different packing motifs. In this work, we highlight the different supramolecular architectures obtained when organometallic moieties crystallize with different solvent molecules. We compare the novel structure of the THF derivative with that of the toluene solvate of a dirhodium(II) complex belonging to a new family of catalyst compounds exhibiting very high performance in arylation processes.
Subject(s)
Organometallic Compounds/chemistry , Crystallization , Crystallography, X-Ray , Furans/chemistry , Hydrogen Bonding , Toluene/chemistryABSTRACT
An efficient new methodology for the arylation of aldehydes is disclosed which uses dirhodium(II) catalysts and N-heterocyclic carbene (NHC) ligands. Complexes of Rh 2(OAc) 4 with one and two NHCs attached on the axial positions were successfully isolated, fully characterized, and used as catalysts in the reaction. The saturated monocomplex ((NHC 5)Rh 2(OAc) 4) 31 was shown to be the most active catalyst and was particularly efficient in the arylation of alkyl aldehydes. DFT calculations support participation of complexes with one axial NHC in the reaction as the catalysts active species and indicate that hydrogen bonds involving dirhodium unit, reactants, and solvent (alcohol) play an important role on the reaction mechanism.