Co-Assembly of Chiral Amines and a Four-Armed Cyano-Substituted Luminophore through Hydrogen Bonds for Potential Development of Smart Chiroptical Materials

Chirality transfer from chiral molecules to assemblies is of vital importance to the design of functional chiral materials. In this work, selective co-assembly behaviors between chiral molecules and an achiral luminophore, potentially driven by the intermolecular salt-bridge type hydrogen bonds are reported. Cyano-substituted tetrakis(arylthio)benzene carboxylic acid ( TA ) served as the luminophore and hydrogen bond donors, which underwent co-assembly with different chiral amines. It was found that structures of chiral amines affect the chirality transfer and the properties of co-assemblies due to effects on hydrogen bonds and stacking pattern. Only in specific co-assemblies, the chiroptical properties occurred at both ground state and excited states based on the emerged Cotton effects and circularly polarized luminescence (CPL) signals, revealing that the chirality was successfully transferred from molecular level to supramolecular level. In addition, accurate quantitative examination of chiral amines was realized by circular dichroism (CD) spectra. This work demonstrates the characteristic chirality response and transfer through co-assembly, providing a potential method to develop smart chiroptical materials.     

Dynamic Covalent Chemistry within Biphenyl Scaffolds: Reversible Covalent Bonding,Control of Selectivity,and Chirality Sensing with a Single System

Axial chirality is a prevalent and important phenomenon in chemistry. Herein we report a combination of dynamic covalent chemistry and axial chirality for the development of a versatile platform for the binding and chirality sensing of multiple classes of mononucleophiles. An equilibrium between an open aldehyde and its cyclic hemiaminal within biphenyl derivatives enabled the dynamic incorporation of a broad range of alcohols, thiols, primary amines, and secondary amines with high efficiency. Selectivity toward different classes of nucleophiles was also achieved by regulating the distinct reactivity of the system with external stimuli. Through induced helicity as a result of central‐to‐axial chirality transfer, the handedness and ee values of chiral monoalcohol and monoamine analytes were reported by circular dichroism. The strategies introduced herein should find application in many contexts, including assembly, sensing, and labeling.     

Dynamic Covalent Chemistry within Biphenyl Scaffolds: Reversible Covalent Bonding,Control of Selectivity,and Chirality Sensing with a Single System

Axial chirality is a prevalent and important phenomenon in chemistry. Herein we report a combination of dynamic covalent chemistry and axial chirality for the development of a versatile platform for the binding and chirality sensing of multiple classes of mononucleophiles. An equilibrium between an open aldehyde and its cyclic hemiaminal within biphenyl derivatives enabled the dynamic incorporation of a broad range of alcohols, thiols, primary amines, and secondary amines with high efficiency. Selectivity toward different classes of nucleophiles was also achieved by regulating the distinct reactivity of the system with external stimuli. Through induced helicity as a result of central‐to‐axial chirality transfer, the handedness and ee values of chiral monoalcohol and monoamine analytes were reported by circular dichroism. The strategies introduced herein should find application in many contexts, including assembly, sensing, and labeling.     

Structurally diverse polyamides obtained from monomers derived via the ugi multicomponent reaction

The combination of the Ugi four-component reaction (Ugi-4CR) with acyclic diene metathesis (ADMET) or thiol-ene polymerization led to the formation of poly-1-(alkylcarbamoyl) carboxamides, a new class of substituted polyamides with amide moieties in the polymer backbone, as well as its side chains. 10-Undecenoic acid, obtained by pyrolysis of ricinoleic acid, the main fatty acid of castor oil, was used as the key renewable building block. The use of different primary amines, as well as isonitriles (isocyanides) for the described Ugi reactions provided monomers with high structural diversity. Furthermore, the possibility of versatile post-modification of functional groups in the side chains of the corresponding polymers should be of considerable interest in materials science. The obtained monomers were polymerized by ADMET, as well as thiol-ene, chemistry and all polymers were fully characterized. Finally, ortho-nitrobenzylamide-containing polyamides obtained by this route were shown to be photoresponsive and exhibited a dramatic change of their properties upon irradiation with light.     

Synthesis of Some Functionalized Peptomers via Ugi Four-Component Reaction

This article describes the synthesis of new peptomers through a simple and efficient route using a one-pot Ugi four-component reaction. The synthesis started from either carboxylic acids or protected amino acids, primary amines, aldehydes, and isocyanides in anhydrous methanol and proceeded under stirring at room temperature. The reaction produced several functionalized peptomers in good yields (67–80%). These compounds are versatile multifunctional intermediates that can be further unprotected or functionalized to generate new molecules with numerous applications in the field of biomedicine.     

A simple synthesis of ferrocenyl bis-amides by a Ugi four-component reaction

An efficient and simple synthesis of ferrocenyl bis-amides by the Ugi four-component reaction of ferrocenecarboxaldehyde, carboxylic acids, isocyanides and amines in methanol at room temperature is reported.     

Chiral Nβ-Fmoc-amino alkyl isonitriles in Ugi-4CR: an assembly of novel 1,1′-iminodicarboxylated peptidomimetics

Enantiopure N^β-Fmoc-amino alkyl isonitriles and amino acid esters have been employed as building blocks in Ugi four-component reaction (U-4CR) to yield 1,1′-iminodicarboxylated peptidomimetics. By employing trifluoroacetic acid as one of the components, a different outcome has been observed and rationalized. Ugi products are obtained as trifluoroacetamide adducts, which on further reaction under mild acidic conditions lead to the title compounds. The method has also been proven to be useful for the preparation of ethyl, benzyl and tert-butyl esters.     

Diastereoselective Ugi reaction without chiral amines: the synthesis of chiral pyrroloketopiperazines

The three-component Ugi reaction with chiral 2-(2-formyl-1H-pyrrol-1-yl)acetic acids prepared from natural l-aminoacids was investigated. The reaction opens a new route to chiral substituted pyrroloketopiperazines. One of the first examples of an asymmetric Ugi reaction without chiral amines is described. The reaction proceeds with moderate diastereoselectivity to give the target compounds in good yields. The scope and limitation of the approach are discussed.     

Determination of Enantiomeric Excess in Amine Derivatives with Molecular Self‐Assemblies

We report the first fluorescence‐based assay for the rapid determination of the ee value of amines, amino alcohols, and amino acid esters. The method uses the self‐assembly of 2‐formylphenylboronic acid with a chiral diol and a chiral amine or derivatives (of unknown chirality) to produce two diastereomeric iminoboronates that differ in their fluorescence intensity and polarization. The approach allows for the accurate determination of the ee value of chiral amines with errors of just 1–2 %. We believe that this application of orthogonal dynamic covalent self‐assembly in the determination of the enantioselectivity will lead to the development of high‐throughput procedures for the determination of chirality.     

A novel highly selective chiral auxiliary for the asymmetric synthesis of L- and D-alpha-amino acid derivatives via a multicomponent Ugi reaction

This paper describes the synthesis of a bicyclic beta-amino acid scaffold in both pure enantiomeric forms and its application as chiral auxiliary in an intramolecular version of the Ugi multicomponent reaction (U-5C-4CR) to prepare alpha-amino acid derivatives of both D- and L-series in a straightforward and very stereoselective manner. The mild conditions required for the Ugi condensation and for the removal of the chiral auxiliary make this method very attractive to prepare a wide range of differently structured N-alkylated and unalkylated amino acid derivatives.     

Highly substituted pyrrolidinones and pyridones by 4-CR/2-CR sequence

[reaction: see text] By combining a Ugi four-component reaction of isocyanides, phosphonoacetic acids, primary amines, and glyoxals or alternatively 3-keto aldehydes with a subsequent Wittig ring-closing reaction (using the Horner/Wadsworth/Emmons variant (HWE)), highly substituted 5-oxo-2,5-dihydro-1H-pyrrole-2-carboxylic acid amides and 6-oxo-1,2,3,6-tetrahydro-pyridine-2-carboxylic acid amides can be assembled, respectively. The corresponding tandem of a Passerini reaction on 3-keto aldehydes and subsequent Wittig ring closure does not afford the expected six-membered 6-oxo-3,6-dihydro-2H-pyran-2-carboxylic acid amides but instead leads to the formation of 4-oxo-pent-2-enoic acid amides via an elimination route.     

Synthesis of diverse phenylglycine derivatives via transformation of Ugi four-component condensation primary adducts

3-(N-Substituted)amino-4-arylamino-1H-isochromenones (isocoumarins) which can be regarded as the enediamine tautomers of the Ugi four-component condensation primary adducts between 2-formylbenzoic acids, arylamines, and isocyanides undergo a facile ring cleavage with amines to give a series of phenylglycine derivatives. Thus, a synthetically useful post-condensation transformation of Ugi four-component condensation primary adducts is described for the first time.     

Supramolecular chirogenesis in zinc porphyrins: mechanism, role of guest structure, and application for the absolute configuration determination.

The achiral syn folded (face-to-face conformation) host molecule of the ethane-bridged bis(zinc porphyrin) transforms into the corresponding chiral extended anti bis-ligated species in the presence of enantiopure amine guests. The mechanism of the supramolecular chirogenesis is based upon the screw formation in bis(zinc porphyrin), arising from steric interactions between the largest substituent at the ligand's asymmetric carbon and peripheral alkyl groups of the neighboring porphyrin ring pointing toward the covalent bridge. The screw direction is determined by the guest's (amines) absolute configuration resulting in a positive chirality induced by (S)-enantiomers due to formation of the right-handed screw, and a negative chirality produced by the left-handed screw of (R)-enantiomers. The screw magnitude is strongly dependent upon the structure of the chiral guests. The amines with bulkier substituents result in stronger CD signals and larger (1)H NMR resonance splittings of enantiotopic protons. This system possesses a high degree of chiroptical activity, which allows the differentiation of one of the smallest homologous elements of organic chemistry, that is, the methyl and ethyl groups attached to the asymmetric carbon, and additionally, which senses a remote chiral center at a position beta to the amine binding group.     

Synthesis of Chiral Resorcinarene-based Hosts and a Mass Spectrometric Study of their Chemistry in Solution and the Gas Phase

The syntheses and characterization of new chiral tetrabenzoxazine and tetrakis-(dialkylaminomethyl) resorcinarenes can be achieved through the reaction of resorcinarene with chiral amines and formaldehyde. In order to examine their host–guest chemistry, chiral quaternary ammonium guests were synthesized by methylation of different amines and amino acid methyl esters through a reductive methylation followed by addition of methyl iodide. Subsequent anion exchange of the iodide against tetraphenylborate helps to improve solubility of the salts in organic solvents. After characterization in solution, mass spectrometry is used to examine the resorcinarenes’ chemistry in the gas phase. Interesting implications of the fragmentation behavior for their solution phase chemistry arise, for which a first example is presented. Ammonium ion binding is indicated by mass spectrometry. Nevertheless, chiral recognition between the chiral hosts and pseudoracemic 1:1 mixtures of appropriately deuterium-labeled chiral guest cations is however not observed.     

Enantioselective CD analysis of amino acids based on chiral amplification with a stereodynamic probe

The condensation between stereolabile 1,8-bis(3′-formyl-4′-hydroxyphenyl)naphthalene, 1, and two amino acid molecules results in the formation of chiral diimines exhibiting strong CD signals. This reaction has been used to develop a chiroptical sensing method for the determination of the absolute configuration and enantiomeric composition of unprotected amino acids. This sensing approach is based on distinctive chiral amplification due to central-to-axial chirality induction within the diimine scaffold formed and does not require the use of an enantiopure ligand or metal complex.     

Three‐Component Asymmetric Catalytic Ugi Reaction—Concinnity from Diversity by Substrate‐Mediated Catalyst Assembly

The first chiral catalyst for the three‐component Ugi reaction was identified as a result of a screen of a large set of different BOROX catalysts. The BOROX catalysts were assembled in situ from a chiral biaryl ligand, an amine, water, BH₃?SMe₂ , and an alcohol or phenol. The catalyst screen included 13 different ligands, 12 amines, and 47 alcohols or phenols. The optimal catalyst system (LAP 8‐5‐47) provided α‐amino amides from an aldehyde, a secondary amine, and an isonitrile with excellent asymmetric induction. The catalytically active species is proposed to be an ion pair that consists of the chiral boroxinate anion and an iminium cation.     

Driving Helical Packing of a Cyanine Dye on Dendron Nanofiber: Gel‐Shrinkage‐Triggered Chiral H‐Aggregation and Enhanced Enantiodiscrimination

An intelligent molecular hydrogel with a volume phase transition was constructed to regulate the chiral packing of a well‐known cyanine dye on a dynamically self‐assembled chiral nanofiber by using a pH trigger. During the shrinkage of the gel, the chiral nanofiber hierarchically assembled into a superhelix and simultaneously drove the dye molecules to stack, from a predominantly monomer form, in an unexpected helical H‐aggregation manner. Through such a transformation, the supramolecular chirality of the system was significantly enhanced and a new property of visual discrimination for chiral amines emerged.     

Trimesic acid is a suitable building block in triple four-component Ugi reaction: access to unique trivalent compounds

Monatshefte für Chemie - Chemical Monthly - A triple four-component Ugi reaction of isocyanide, amine, aldehyde, and trimesic acid as the acid component with three acidic functional groups in...     

Ugi/Smiles access to pyrazine scaffolds

New pyrazine and quinoxaline scaffolds were obtained via an Ugi/Smiles four-component coupling of pyrazinone or quinoxalinone derivatives with isocyanides, aldehydes, and primary amines.     

A novel one-pot synthesis of highly diverse indole scaffolds by the Ugi/Heck reaction

A novel one-pot two-step multi component reaction of acrylic aldehydes, bromoanilines, acids and isocyanides yielding polysubstituted indoles is described. The reaction is based on the combination of an Ugi four-component reaction followed by an intramolecular Heck-reaction. The simultaneous use of formic acid and cinnamaldehydes affords in situ generation of 1H-indoles. Convertible isocyanides can also be used with success in this Ugi/Heck strategy and enable synthesis of 1H-indole-2-carboxylic acid building blocks.