Chiral Research Articles

Theoretical Study of the Addition of Cu-Carbenes to Acetylenes to Form Chiral Allenes.

Terminal alkynes have become one of the most versatile building blocks for C-C bond construction in the past few decades, and they are usually considered to convert to acetylides before further transformations. In this study, a novel direct nucleophilic addition mode for Cu(I)-catalyzed cross-coupling of terminal alkynes and N-tosylhydrazones to synthesize chiral allenes is proposed, and it was investigated by density functional theory with the M11-L density functional. Three different reaction pathways were considered and investigated. The computational results show that the proposed reaction pathway, which includes direct nucleophilicattack of protonated acetylene, deprotonation of the vinyl cation, and catalyst regeneration, is the most favorable pathway. Another possible deprotonation-carbenation-insertion pathway is shown to be unfavorable. The direct nucleophilic addition step is the rate- and enantioselectivity-determining step in the catalytic cycle. Noncovalent interaction analysis shows that the steric effect between the methyl group of the carbene moiety and the naphthalyl group of the bisoxazoline ligand is important to control the enantioselectivity. In addition, calculation of a series of chiral bisoxazoline ligands shows that a bulky group on the oxazoline ring is favorable for high enantioselectivity, which agrees with experimental observations. Moreover, copper acetylides are stable, and their generation is a favorable pathway in the absence of chiral bisoxazoline ligands.

Photo-responsive dye-doped liquid crystals for smart windows.

An electric field drives most dye-doped liquid crystal devices. Here, we demonstrate a new photo-responsive dye-doped self-organized cholesteric liquid crystal device. Upon UV or blue light exposure, the helical twisting power of the chiral azobenzene changes because of the trans-cis isomerization. As a result, the initially vertically aligned liquid crystal directors and dye molecules will change from transparent state to dark state. Such a polarizer-free photo-activated dimmer can be used for wide range of applications, such as diffractive photonic devices, portable information system, vehicular head-up displays, and as a smart window for energy-saving buildings.

Catalytic enantioselective construction of axial chirality in 1,3-disubstituted allenes

Metal-catalyzed enantioselective construction of the loosening axial allene chirality spreading over three carbon atoms using a chiral ligand is still a significant challenge. In the literature, steric effect of the substrates is the major strategy applied for such a purpose. Herein, we present a general palladium-catalyzed asymmetrization of readily available racemic 2,3-allenylic carbonates with different types of non-substituted and 2-substituted malonates using (R)-(−)-DTBM-SEGPHOS as the preferred ligand to afford 1,3-disubstituted chiral allenes with 90~96% ee. This protocol has been applied to the first enantioselective synthesis of natural product, (R)-traumatic lactone. Control experiments showed that in addition to the chiral ligand, conducting this transformation via Procedure C, which excludes the extensive prior coordination of the allene unit in the starting allene with Pd forming a species without the influence of the chiral ligand, is crucial for the observed high enantioselectivity.

Synthesis of Chiral Alkylboronic Esters via Carbosulfenylation

Synthesis of Chiral Alkylboronic Esters via Carbosulfenylation

Synthesis of chiral allene moiety from Morita–Baylis–Hillman adduct of isatin derivatives via Claisen rearrangement

Chiral allenes are synthesized from Morita–Baylis–Hillman adduct of isatin derivatives via Claisen rearrangement for the first time. The chiral 1,3-substituted allene entity is achieved using (R)-but-3-yn-2-ol. The details of the work are elaborately discussed in this letter.

Catalytic Regio- and Enantioselective Proton Migration from Skipped Enynes to Allenes

Summary Chiral allenes are highly valuable as versatile synthetic intermediates and core skeletons of various functional organic molecules. Despite marked recent advances, the straightforward catalytic enantioselective synthesis of hydrocarbon allenes from readily available starting materials without relying on polar functional groups is still very challenging. Here, we report a copper(I)-catalyzed enantioselective proton migration from skipped enynes to allenes as an efficient approach in chiral allene synthesis. With catalyst loading as low as 0.5 mol %, the reaction proceeds smoothly under mild conditions without the need for additional stoichiometric reagents or generation of waste. Novel chiral ligand L6 plays a critical role in furnishing high catalyst activity, promoting regioselective protonation to produce allenes instead of conjugated enynes, and inducing axial chirality of allenes. The multiple roles of the chiral ligand are rationalized by density functional theory calculations.

Theoretical analysis of chirality and scale effects on critical bucklingload of zigzag triple walled carbon nanotubes under axial compression embedded in polymeric matrix

Using the non-local elasticity theory, Timoshenko beam model is developed to study the non- local buckling of Triple-walled carbon nanotubes (TWCNTs) embedded in an elastic medium under axial compression. The chirality and small scale effects are considered. The effects of the surrounding elastic medium based on a Winkler model and van der Waals\'(vdW) forces between the inner and middle, also between the middle and outer nanotubes are taken into account. Considering the small-scale effects, the governing equilibrium equations are derived and the critical buckling loads under axial compression are obtained. The results show that the critical buckling load can be overestimated by the local beam model if the small-scale effect is overlooked for long nanotubes. In addition, significant dependence of the critical buckling loads on the chirality of zigzag carbon nanotube is confirmed. Furthermore, in order to estimate the impact of elastic medium on the non-local critical buckling load of TWCNTs under axial compression, the use of these findings are important in mechanical design considerations, improve and reinforcement of devices that use carbon nanotubes.

Catalytic deracemization of chiral allenes by sensitized excitation with visible light.

Chiral compounds exist asenantiomers that are non-superimposable mirror images of each other. Owing to the importance of enantiomerically pure chiral compounds1-for example, as active pharmaceutical ingredients-separation of racemates (1:1 mixtures of enantiomers) is extensively performed2. Frequently, however, only a single enantiomeric form of a chiral compound is required, which raises the question of how a racemate can be selectively converted into a single enantiomer. Such a deracemization3 process is entropically disfavoured and cannot be performed by a conventional catalyst in solution. Here we show that it is possible to photochemically deracemize chiral compounds with high enantioselectivity using irradiation with visible light (wavelength of 420 nanometres) in the presence of catalytic quantities (2.5 mole per cent) of a chiral sensitizer. We converted an array of 17 chiral racemic allenes into the respective single enantiomers with 89 to 97 per cent enantiomeric excess. The sensitizer is postulated to operate by triplet energy transfer to the allene, with different energy-transfer efficiencies for the two enantiomers. It thus serves as a unidirectional catalyst that converts one enantiomer but not the other, and the decrease in entropy is compensated by light energy. Photochemical deracemization enables the direct formation of enantiopure materials from a racemic mixture of the same compound, providing a novel approach to the challenge of creating asymmetry.

Water-Soluble Palladium Complex of N′-(pyridin-2-yl)propane-1,3-diamine modified β-Cyclodextrin: An efficient Catalyst for Transfer Hydrogenation of Carbonyl Compounds

Synthesis of a water-soluble Pd(II) complex of N′-(pyridin-2-yl)propane-1,3-diamine modified β-cyclodextrin (Pd(II)@PyPDA:β-CD) is reported. The synthesized Pd(II)@PyPDA:β-CD, characterized by FT–I...

Catalytic asymmetric synthesis of chiral trisubstituted heteroaromatic allenes from 1,3-enynes

Chiral allene and N-heteroaryl motifs are present in an ever-growing list of biologically active natural products and synthetic drugs. Although significant progress has been made in asymmetric syntheses of chiral allenes, general and practical protocols for enantioselective syntheses of chiral N-heteroaryl-substituted allenes from readily available starting materials still remain rare. Here we report a highly enantioselective synthesis of quinolinyl-substituted chiral allenes through a copper-catalyzed asymmetric allenylation of quinoline N-oxides with readily available 1,3-enynes. A variety of 1,3-enynes react with quinoline N-oxides, affording the corresponding quinolinyl-substituted allenes in high yields (up to 95%) and high enantioselectivities (up to 99% ee). This transformation tolerates a variety of functional groups, such as chloro, bromo, trifluoromethyl ether, tertiary amine, siloxy, carboxylic ester, imide, pyridine, and thiophene moieties. DFT calculations suggest a pathway involving an intramolecular nucleophilic addition of an allenyl copper intermediate with a coordinated quinoline N-oxide through a five-membered, rather than seven-membered, transition state.

Enhancing the Activity of LkTADH by Site-Directed Mutagenesis to Prepare Key Chiral Block of Statins

Enhancing the Activity of LkTADH by Site-Directed Mutagenesis to Prepare Key Chiral Block of Statins

Enantio- and Diastereoselective Synthesis of Chiral Allenes by Palladium-Catalyzed Asymmetric [3+2] Cycloaddition Reactions.

A protocol for the asymmetric synthesis of highly substituted chiral allenes with control of point and axial chirality has been developed. A palladium-catalyzed [3+2] cycloaddition using readily available racemic allenes gives access to densely functionalized chiral allenes with excellent yields and functional group tolerance. The catalytic asymmetric protocol utilizes a broad range of allenyl TMM (trimethylenemethane) donors to form cyclopentanes, pyrrolidines, and spirocycles with very good control of regio-, enantio-, and diastereoselectivity. The chiral allene moiety is shown to be a valuable functional group for rapid elaboration towards complex targets.

Enantio‐ and Diastereoselective Synthesis of Chiral Allenes by Palladium‐Catalyzed Asymmetric [3+2] Cycloaddition Reactions

AbstractA protocol for the asymmetric synthesis of highly substituted chiral allenes with control of point and axial chirality has been developed. A palladium‐catalyzed [3+2] cycloaddition using readily available racemic allenes gives access to densely functionalized chiral allenes with excellent yields and functional group tolerance. The catalytic asymmetric protocol utilizes a broad range of allenyl TMM (trimethylenemethane) donors to form cyclopentanes, pyrrolidines, and spirocycles with very good control of regio‐, enantio‐, and diastereoselectivity. The chiral allene moiety is shown to be a valuable functional group for rapid elaboration towards complex targets.

Enantioseparation and purity determination of Ondansetron by amylose based Chiral HPLC method: A Chemometric approach

Amylose based chiral HPLC method for enantioselective separation of ondansetron was developed, optimized and validated on Chiral Pak AS-3R analytical column (150 mm × 4.6 mm i.d., 3 μm). Mobile phase comprising of Acetonitrile: 0.2% Triethylamine: Methanol (15.49:30:54.51) and at a flow rate of 1.33mL/min. The separation was detected at a wavelength of 254 nm and run time was achieved within 6.0 min. Applied Central composite design (CCD) to validate the impact of three independent variables: 0.2% triethylamine (TEA), Acetonitrile (ACN) and flow rate (FL) keeping the methanol concentration constant and the responses selected were capacity factor (k1), resolution (Rs2,1), and retention time (tR2). Using this approach, a mathematical model was elucidated and response surface plots were acquired for the separation. CCD results were integrated into a multi-criteria decision-making approach in order to prevail a set of optimal experimental conditions directing to the most desirable compromise between resolution and analysis time. This method can be applied for the routine analysis.

Chiral Amidophosphate-Induced Halooxy- and Haloazacyclizations

Chiral Amidophosphate-Induced Halooxy- and Haloazacyclizations

Organocatalytic Formation of Chiral Trisubstituted Allenes and Chiral Furan Derivatives.

A novel reaction that provides chiral allenes by amino catalytic activation of either aldehydes or α,β-unsaturated aldehydes for reaction with alkynyl-substituted enones is presented. The reaction forms a variety of trisubstituted allenes in high yields and with excellent stereoselectivities. The utility of the reaction concept is demonstrated by the synthesis of chiral furan derivatives in high yields and stereoselectivities.

Organocatalytic Formation of Chiral Trisubstituted Allenes and Chiral Furan Derivatives

AbstractA novel reaction that provides chiral allenes by amino catalytic activation of either aldehydes or α,β‐unsaturated aldehydes for reaction with alkynyl‐substituted enones is presented. The reaction forms a variety of trisubstituted allenes in high yields and with excellent stereoselectivities. The utility of the reaction concept is demonstrated by the synthesis of chiral furan derivatives in high yields and stereoselectivities.

Enantiodivergent Synthesis of Allenes by Point‐to‐Axial Chirality Transfer

AbstractAn enantiodivergent method for the synthesis of multiply substituted allenes is described. Highly enantioenriched, point‐chiral boronic esters were synthesized by homologation of α‐seleno alkenyl boronic esters with lithiated carbamates and eliminated to form axially chiral allene products. By employing either oxidative or alkylative conditions, both syn and anti elimination could be achieved with complete stereospecificity. The process enables the synthesis of either M or P allenes from a single isomer of a point‐chiral precursor and can be employed for the enantioselective assembly of di‐, tri‐, and tetrasubstituted allenes.

Enantiodivergent Synthesis of Allenes by Point-to-Axial Chirality Transfer.

An enantiodivergent method for the synthesis of multiply substituted allenes is described. Highly enantioenriched, point‐chiral boronic esters were synthesized by homologation of α‐seleno alkenyl boronic esters with lithiated carbamates and eliminated to form axially chiral allene products. By employing either oxidative or alkylative conditions, both syn and anti elimination could be achieved with complete stereospecificity. The process enables the synthesis of either M or P allenes from a single isomer of a point‐chiral precursor and can be employed for the enantioselective assembly of di‐, tri‐, and tetrasubstituted allenes.

An analysis of the hadron structure in covariant chiral effective theory

An analysis of the hadron structure in covariant chiral effective theory