Chiral Derivatives Research Articles

One-step selective synthesis of doubly and triply fused chiral boroloborole derivatives

Chiral 3a,6a-dihydroborolo[3,2-b]boroles are obtained in one diastereoselective step from the reactions of ortho-(dihaloboryl)arenes with stannole derivatives via a complex rearrangement of 1-borolyl-2-(dihaloboryl)arene intermediates.

Chiral phosphoric acid catalyzed enantioselective inverse-electron-demand oxa-Diels–Alder reactions to synthesize chiral tricyclic tetrahydropyran derivatives

A series of enantioenriched trans-fused octahydropyranofuran or octahydropyranopyran-containing tricyclic derivatives were accessed through chiral phosphoric acid catalyzed IEDODA reactions.

A hybrid Au/Ru catalyst for sequential alkyne hydration/asymmetric transfer hydrogenation reactions

A hybrid catalytic system was developed for sequential alkyne hydration/asymmetric transfer hydrogenation reactions through the confinement of an amphiphilic polymer supported ruthenium and gold catalysts within core/shell silica gel.

Circularly polarised luminescence from intramolecular excimer emission of bis-1,8-naphthalimide derivatives.

Chiral excimers exhibit unique photophysical behaviour. However, further molecular design is required along with systematic studies on the effect of spacer groups and solvent polarity. In this study, we prepared four circularly polarised luminescence (CPL)-active molecules that exhibit intramolecular excimer emission. Bis-1,8-naphthalimide (bNI) derivatives D-LybNI, L-LybNI, D-LyMebNI, and L-LyMebNI were prepared with chiral backbones and alkyl linkages between the NI rings with chain lengths of five carbon atoms, suitable for excimer fluorescence. The fluorescence properties were investigated experimentally and theoretically using density functional theory. The molecules exhibited intramolecular excimer fluorescence in polar organic solvents. Mirror-image circular dichroism and CPL spectra were obtained for the D and L forms. D- and L-LyMebNI exhibited relatively large luminescence dissymmetry factors (|glum|) in acetonitrile of 1.9 × 10-3 and 1.6 × 10-3, respectively. Thus, this study demonstrates chiral bNI derivatives with simple synthesis procedures that emit intramolecular excimer fluorescence and have effective CPL properties. These molecules are promising for developing organic molecular systems with bright, highly polarised emission.

Catalytic asymmetric ring-opening of aminocyclopropanes with oxygen nucleophiles: access to chiral γ-amino acid derivatives

Donor–acceptor aminocyclopropanes bearing both amino and carboxyl groups underwent catalytic asymmetric ring-opening reactions with diverse oxygen nucleophiles to afford chiral γ-oxygen-substituted γ-aminobutyric acid derivatives with good results.

Palladium-catalyzed enantioselective umpolung allylation of amido-tethered allylic carbonates with isatin-derived ketimines.

A palladium-catalyzed enantioselective umpolung allylation reaction of amido-tethered allyl carbonates with N-2,2,2-trifluoroethylisatin ketimines has been realized herein. The reaction worked well under mild reaction conditions to give various chiral oxindole derivatives in moderate to excellent yields with high enantioselectivities. Notably, this work represents the first Pd-catalyzed asymmetric umpolung allylation reaction of N-2,2,2-trifluoroethylisatin ketimines.

Ultraviolet circularly polarized light detection based on chiral BN-anthracene derivatives

BN-anthracene derivatives have been synthesized as novel visible-blind ultraviolet-absorbing chiral materials for ultraviolet circularly polarized light detection.

Strong chiroptical properties from thin films of chiral imidazole derivatives allowing for easy detection of circularly polarized luminescence

We report the synthesis and characterization of four similar chiral 1-methyl-1H-imidazole π-conjugated derivatives. In particular, we focus on the thin film chiroptical characterization (electronic circular dichroism and circular polarized luminescence),...

Rational design of naphthoquinone-based antibacterial agents through iridium-catalyzed enantioselective β-allenylation of 2-hydroxynaphthoquinones

The first Ir-catalyzed enantioselective β-allenylation of 2-hydroxynaphthoquinones is developed. The β-allenylic lawsone derivatives displayed remarkable potency against Gram-positive MRSA strain and low toxicity against mammalian cell lines.

Highly efficient synthesis of enantioenriched vicinal halohydrins via Ir-catalyzed asymmetric hydrogenation using dynamic kinetic resolution.

A novel synthetic route was developed for the construction of chiral cis-vicinal halohydrins derivatives through Ir/f-phamidol-catalysed asymmetric hydrogenation of corresponding α-halogenated ketones with high yields (up to 99% yield), excellent diastereoselectivities (>20 : 1 dr), enantioselectivities (up to 99% ee), and high substrate catalyst ratio (S/C = 1000).

Correction: Ethanol-assisted mechanochemical asymmetric cross-dehydrogenative coupling reaction with recoverable chiral amine/NaCl for accessing chiral α-alkyl α-glycine derivatives

Correction for ‘Ethanol-assisted mechanochemical asymmetric cross-dehydrogenative coupling reaction with recoverable chiral amine/NaCl for accessing chiral α-alkyl α-glycine derivatives’ by Jingbo Yu et al., Green Chem., 2024, https://doi.org/10.1039/d4gc00947a.

Fe-BPsalan complex catalyzed asymmetric vinylogous Mukaiyama–Michael reaction of silyloxyfuran and α, β-unsaturated acyl imidazoles with high enantioselectivity and diastereoselectivity

An efficient iron catalyzed asymmetric vinylogous Mukaiyama–Michael reaction of silyloxyfuran and α, β-unsaturated acyl imidazoles was developed to afford chiral γ-butenolide derivatives (25 examples) in moderate to good yields (up...

Enantioselective synthesis of 4-aryl-3,4-dihydrocoumarins via N-heterocyclic carbene catalyzed β-arylation/cyclization of α-bromoenals.

4-Aryl-3,4-dihydrocoumarins are one of the most important structural motifs. Herein, we disclose an enantioselective N-heterocyclic carbene catalyzed β-arylation/cyclization of α-bromoenals with 3-aminophenols under mild conditions. The protocol allows for the rapid preparation of 4-aryl-3,4-dihydrocoumarins in acceptable yields with good enantioselectivities. The products of this reaction could be converted into chiral diarylpropanoic acid derivatives without erosion of the enantioselectivity.

Well-defined chiral dinuclear copper-catalyzed tandem asymmetric propargylic amination–carboxylative cyclization sequence toward chiral 2-oxazolidinone derivatives

A variety of chiral 2-oxazolidinones was obtained via a dinuclear copper-catalyzed asymmetric propargylic amination–carboxylative cyclization sequence of propargylic esters with alkyl amine hydrochlorides and CO2.

Ethanol-assisted mechanochemical asymmetric cross-dehydrogenative coupling reaction with recoverable chiral amine/NaCl for accessing chiral α-alkyl α-glycine derivatives

Ethanol-assisted grinding effectively facilitated aerobic asymmetric cross-dehydrogenative coupling of glycine esters/amides with ketones/aldehydes, deploying reusable chiral amine/NaCl for rapid synthesis of chiral α-alkyl α-glycine derivatives.

Molecular ordering-enhanced circularly polarized luminescence of chiral 1,10-phenanthroline derivatives.

2,9-Bis((1R,2S,5R)-2-isopropyl-5-methylcyclohexanoxy)-1,10-phenanthroline [2,9-di-L-menthoxy-1,10-phenanthroline] (Men2Phen) and 2,9-bis(2-(S)-methylbutoxy)-1,10-phenanthroline (MB2Phen) were synthesized as chiral derivatives of 1,10-phenanthroline (Phen). Differences in rigidity and bulkiness of the chiral substituents at the 2- and 9-positions of the Phen backbone led to distinctive molecular dissymmetry in the ground state resulting in remarkable differences in circular dichroism. Men2Phen exhibited efficient circularly polarized luminescence (CPLm) at an anisotropy factor of 10-2 in the solid state based on molecular ordering disclosed by X-ray crystal analysis, while it showed much lower anisotropy factor in solution. MB2Phen, which was rather amorphous and did not afford good crystals, showed only negligible CPLm both in the solid state and in solution.

Homochiral vs. heterochiral preference in chiral self-recognition of cyclic diols.

The structure and clustering propensity of a chiral derivative of cis-1,2-cyclohexanediol, namely, 1-phenyl-cis-1,2-cyclohexanediol (cis-PCD), has been studied under supersonic expansion conditions by combining laser spectroscopy with quantum chemistry calculations. The presence of the phenyl substituent induces conformational locking relative to cis-1,2-cyclohexanediol (cis-CD), and only one conformer of the bare molecule is observed by both Raman and IR-UV double resonance spectroscopy. The homochiral preference inferred for the dimer formation at low enough temperature is in line with the formation of a conglomerate in the solid state. The change in clustering propensity in cis-PCD relative to trans-1,2-cyclohexanediol (trans-CD), which shows heterochiral preference, is explained by the presence of the phenyl substituent rather than the effect of cis-trans isomerism. Indeed the transiently chiral cis-CD also forms preferentially heterodimers, whose structure is very close to that of the corresponding trans-CD dimer.

A Simple Chiral 1H NMR Method for the Discrimination of (R)- and (S)-Cannabichromene in Complex Natural Mixtures and Their Effects on TRPA1 Activity.

In recent years, the enantiomeric ratio of cannabichromene (CBC) within the cannabis plant has attracted significant attention. Cannabichromene is one of the well-known cannabinoids found in cannabis, along with THC (tetrahydrocannabinol) and CBD (cannabidiol). Cannabichromene exists as a scalemic mixture, meaning it has two enantiomers, (S)-cannabichromene and (R)-cannabichromene, with the ratio between these enantiomers varying among different cannabis strains and even within individual plants. This study presents an accurate and robust chiral NMR method for analyzing cannabichromene's enantiomeric ratio, a well-investigated cannabinoid with numerous pharmacological targets. The use of Pirkle's alcohol as the chiral solvating agent (CSA) or, alternatively, the use of (S)-ibuprofen as a chiral derivatizing agent (CDA) facilitated this analysis. Moreover, the chiral NMR method proves to be a user-friendly tool, easily applicable within any NMR facility, and an expanded investigation of cannabichromene chirality may provide insights into the origin, cultivation, treatment, and processing of Cannabis sativa plants. This study also undertakes a pharmacological examination of the (R)- and (S)-cannabichromenes concerning their most extensively studied pharmacological target, the TRPA1 channels, with the two enantiomers showing the same strong agonistic effect as the racemic mixture.

Design, enantioselective synthesis, and antiviral activities against potato virus Y of axially chiral thiazine derivatives

AbstractA series of novel thiazine derivatives featuring axial chirality in both (R) and (S) configurations were successfully synthesized by N‐heterocyclic carbene (NHC)‐catalyzed enantioselective [3 + 3] annulations, and their potential as anti‐plant virus agents against potato virus Y (PVY) was evaluated. Biological activity results demonstrated that most of these chiral thiazine derivatives exhibited significant activities against PVY. Notably, compound (S)‐3g displayed a remarkable 58% inactivation effect against PVY at a concentration of 500 μg/mL, slightly surpassing the effectiveness of Ningnanmycin (NNM) at 57%. Additionally, (S)‐3g exhibited curative activity of 57%, which is superior to NNM (53%). Molecular docking studies revealed preliminary insights into the distinct biological properties of the two different enantiomers, (R) or (S)‐3g against PVY, wherein single enantiomer (S)‐3g formed a more stable interaction with PVY‐CP, as indicated by its lower binding free energy (−41.18 kcal/mol) compared to (R)‐3g (−36.9 kcal/mol). The findings in this study with a new class of axially chiral thiazine derivatives shall inspire further development of chiral heterocycles as potential drug candidates for the protection of plant virus infections.

Investigation of the Binary System of Proxyphylline Enantiomers: Structural Resolution and Phase Diagram Determination.

The solid-state landscape of proxyphylline (PXL), a chiral derivative of theophylline crystallizing as a racemic compound, was extensively investigated by means of thermal analyses and diffraction techniques. This study revealed the presence of five distinct polymorphic forms that were characterized: two polymorphs of the racemic mixture and three polymorphs of the pure enantiomer. The nature of each solid phase was confirmed by combining the different analytical techniques, revealing the presence of a thermodynamically stable racemic compound, RI (TFus= 134 °C), in equilibrium with the stable enantiopure crystal form, EI (TFus = 148.3 °C). Additionally, other crystal forms could be evidenced: a polymorph of the racemic compound, RII (TFus= 111.5 °C), as well as two metastable conglomerates, cEI and cEII, and two other polymorphs of the pure enantiomer, EII and EIII. The crystal structures of RI and EI are reported and discussed, highlighting the diversity of molecular conformations that can be adopted by the PXL molecule, which accounts for the versatility of the crystallization behaviors observed in this system. These findings enhance our understanding of the crystallization behavior of chiral pharmaceutical compounds and have implications for optimizing their crystallization processes in the pharmaceutical industry.