Asymmetric Induction Research Articles

Acetylene Derivatives of Cationic Diazaoxatriangulenes and Diaza [4]Helicenes ‐ Access to Red Emitters and Planar Chiral Stereochemical Traits

Cationic triangulenes, and related helicenes, constitute a rich class of dyes and fluorophores, usually absorbing and emitting light at low energy, in the orange to red domains. Recently, to broaden the scope of applications, regioselective late‐stage functionalizations on these core moieties have been developed. For instance, with the introduction of electron‐donating groups (EDGs), important bathochromic shifts are observed pushing absorptions towards or in the near‐infrared (NIR) spectral domain while emissive properties disappear essentially completely. Herein, to upset this drawback, acetylene derivatives of cationic diazaoxa triangulenes (DAOTA) and [4]helicenes are prepared (16 examples). Contrary to other EDG‐functionalized derivatives, C≡C− functionalized products remain broadly fluorescent, with red‐shifted absorptions (Δλ abs up to 25 nm) and emissions (Δλ em up to 73 nm, Φ PL up to 51 %). Quite interestingly, a general dynamic stereoisomerism phenomenon is evidenced for the compounds derived from achiral DAOTA cores. At low temperature in 1H NMR spectroscopy (218 K), N−CH2 protons become diastereotopic with chemical shifts differences (Δδ) as high as +1.64 ppm. The signal coalescence occurs around 273 K with a barrier of ∼12 kcal mol−1. This phenomenon is due to planar chiral conformations (S p and R p configurations), induced by the geometry of the alkyl (n‐propyl) side‐chains next to the acetylenic substituents. Ion pairing studies with Δ‐TRISPHAT anion not only confirm the occurrence of the chiral conformations but evidence a moderate but definite asymmetric induction from the chiral anion onto the cations. Finally, DFT calculations offer a valuable insight on the geometries, the corresponding stereodynamics and also on the very large difference in NMR for some of the diastereotopic protons.

Synthesis of β-Silyl-α-amino Acid Derivatives by Cu-Catalyzed Regio- and Enantioselective Silylamination of α,β-Unsaturated Esters.

A copper-catalyzed silylamination of α,β-unsaturated esters with silylboranes and hydroxylamines has been developed to afford the corresponding β-silyl-α-amino acid derivatives, which are of great interest in medicinal and pharmaceutical chemistry. Additionally, by using a suitable chiral bisphosphine ligand, the asymmetric induction is possible, delivering the optically active β-silyl-α-amino acids with synthetically acceptable diastereomeric ratios (55:45-82:18 dr) and high enantiomeric ratios (81:19-99:1 er).

Circularly Polarized Light Can Override and Amplify Asymmetry in Supramolecular Helices.

Circularly polarized light (CPL) is an inherently chiral entity and is considered one of the possible deterministic signals that led to the evolution of homochirality. While accumulating examples indicate that chirality beyond the molecular level can be induced by CPL, not much is yet known about circumstances where the spin angular momentum of light competes with existing molecular chiral information during the chirality induction and amplification processes. Here we present a light-triggered supramolecular polymerization system where chiral information can both be transmitted and nonlinearly amplified in a "sergeants-and-soldiers" manner. While matching handedness with CPL resulted in further amplification, we determined that opposite handedness could override molecular information at the supramolecular level when the enantiomeric excess was low. The presence of a critical chiral bias suggests a bifurcation point in the homochirality evolution under random external chiral perturbation. Our results also highlight opportunities for the orthogonal control of supramolecular chirality decoupled from molecular chirality preexisting in the system.

Enantioselective Biginelli Reaction Catalyzed by (L)‐Prolinamide Containing Imidazolium Ionic Liquid

Abstract(L)‐Prolinamide containing imidazolium ionic liquids have been synthesized and evaluated as organocatalysts for the asymmetric Biginelli reaction of benzaldehydes, urea, and β‐keto esters. The synthesized chiral ionic liquids were characterized by various techniques such as FT‐NMR, FT‐IR, TGA, and HRMS. The chiral ionic liquid containing adamantyl (L)‐prolinamide having [BF4]‐ anion (5 mol %) and p‐toluenesulfonic acid (5 mol %) as an additive catalyzed the Biginelli reaction and afforded a variety of chiral 3,4‐dihydropyrimidin‐2‐(1H)‐ones (DHPMs) in 16–74 % yields and 7–85 % ee's after 48 h at room temperature and out of 30 chiral DHPMs products, 18 are new. A plausible reaction mechanism and transition states or intermediates have been proposed and supported by FT‐NMR spectroscopy and DFT calculations. The asymmetric induction was favored by the Re‐face attack on the imine bond and the Biginelli products were obtained with (R)‐absolute configuration. The DFT calculations (B3LYP/631‐G*) were performed to find the energy of the intermediates.

Inducing Single-Handed Helicity in a Twisted Molecular Nanoribbon.

Molecular conformation has an important role in chemistry and materials science. Molecular nanoribbons can adopt chiral twisted helical conformations. However, the synthesis of single-handed helically twisted molecular nanoribbons still represents a considerable challenge. Herein, we describe an asymmetric approach to induce single-handed helicity with an excellent degree of conformational discrimination. The chiral induction is the result of the chiral strain generated by fusing two oversized chiral rings and of the propagation of that strain along the nanoribbon’s backbone.

Induction of chiral polymers from metal-organic framework for stereoselective recognition

So far, the fabrication of chiral metal-organic framework (CMOF) is difficult to predict and the chiral functionality mainly comes from the building blocks that is a part of the frameworks. The induction effect in the chiral nanochannels of the metal-organic framework (MOF) makes achiral polymers have chiral properties, which has not been well explored. Therefore, CMOFs with chiral nanochannels or chiral pores appear to have special functions. Herein, CMOFs (D-his-ZIF-8) with chiral micropores or chiral nanochannels are prepared through a simple 2-methyl imidazolate in-situ substitution by d-histidine. The unmodified polyaniline with chirality (c-PANI) was synthesized in chiral nanochannels and pores of CMOF, which brought about chiral induction from the chiral nanochannels and pores of CMOF to c-PANI chains. The circular dichroism shows that the c-PANI chains released from the chiral nanochannel still maintains the chiral properties even leaves the chiral nanochannel. It can be seen from the electrochemical results that c-PANI has excellent conductivity, and the conductivity of CMOF is very poor. Electrochemical recognition showed that both CMOF and c-PANI have certain chiral recognition effects for L-Trp and D-Trp, from which the optimal recognition effect was obtained from c-PANI chains. This shows that the excellent conductivity of c-PANI not only expands the electrochemical signal, but also the helical structure of the c-PANI chains accelerates the distinction of chiral molecules. This study provides a novel perspective to induce chiral polymer chains with better conductivity in the nanochannels of CMOF.

Asymmetric Twisting of C-Centered Octahedral Gold(I) Clusters by Chiral N-Heterocyclic Carbene Ligation.

Asymmetric induction of metal clusters by ligation of chiral ligands is intriguing in terms of the mechanism of chirality transfer and the stability of the resulting chiral structure. Here we report the asymmetric induction of C-centered hexagold(I) CAuI6 clusters into an asymmetrically twisted structure through monodentate, chiral benzimidazolylidene-based N-heterocyclic carbene (NHC) ligands. X-ray diffraction analysis revealed that the NHC-ligated CAuI6 cluster was diastereoselectively twisted with directionally selective, bond length expansion, and contraction of the Au···Au contacts and that the original cluster with high symmetry was transformed into an optically pure, asymmetric CAuI6 cluster with C1 symmetry. Moreover, the circular dichroism spectroscopy and the time-dependent density functional theory calculation confirmed that the asymmetrically twisted CAuI6 structure was maintained even in solution. Such asymmetric induction of configurationally stable metal clusters would greatly expand the molecular design possibilities of asymmetric catalysts and chiroptical materials by utilizing library chiral NHC ligands.

Enantioselective Pictet-Spengler Reaction of Acyclic α-Ketoesters Using Chiral Imidazoline-Phosphoric Acid Catalysts.

The first enantioselective Pictet-Spengler reaction of acyclic α-ketoesters with tryptamines has been developed. Excellent yields and enantioselectivity were obtained for the reaction using chiral imidazoline-phosphoric acid catalysts. Density functional theory calculations suggested possible transition states that explain the origin of chiral induction. This process provides an efficient route for the synthesis of tetrahydro-β-carboline derivatives.

Diastereodivergent Synthesis of (+)‐α‐Conhydrine and (−)‐β‐Conhydrine from a η,γ‐Dibromo‐β‐ketosulfoxide

AbstractDiastereodivergent syntheses of the enantiopure hemlock alkaloid (+)‐α‐conhydrine and its diastereomer (−)‐β‐conhydrine are reported. Our approach relies on efficient Crystallization‐Induced Diastereomer Transformation (CIDT) of an epimeric mixture of a η,γ‐dibromo‐β‐ketosulfoxide, optically pure only at the sulfur atom, that provided a stable α‐bromoketone, and diastereoselective β‐ketosulfoxide reduction that led to the corresponding anti and syn‐bromohydrins with high level of asymmetric induction.

Surfaces Decorated with Enantiomorphically Pure Polymer Nanohelices via Hierarchical Chirality Transfer across Multiple Length Scales.

Mesoscale chiral materials are prepared by lithographic methods, assembly of chiral building blocks, and through syntheses in the presence of polarized light. Typically, these processes result in micrometer-sized structures, require complex top-down manipulation, or rely on tedious asymmetric separation. Chemical vapor deposition (CVD) polymerization of chiral precursors into supported films of liquid crystals (LCs) are discovered to result in superhierarchical arrangements of enantiomorphically pure nanofibers. Depending on the molecular chirality of the 1-hydroxyethyl [2.2]paracyclophane precursor, extended arrays of enantiomorphic nanohelices are formed from achiral nematic templates. Arrays of chiral nanohelices extend over hundreds of micrometers and consistently display enantiomorphic micropatterns. The pitch of individual nanohelices depends on the enantiomeric excess and the purity of the chiral precursor, consistent with the theoretical model of a doubly twisted LC director configuration. During CVD of chiral precursors into cholesteric LC films, aspects of molecular and mesoscale asymmetry combine constructively to form regularly twisted nanohelices. Enantiomorphic surfaces permit the tailoring of a wide range of functional properties, such as the asymmetric induction of weak chiral systems.

Highly Phosphorescent Planar Chirality by Bridging Two Square-Planar Platinum(II) Complexes: Chirality Induction and Circularly Polarized Luminescence.

Chiral organometallic complexes have demonstrated many potential and practical applications. However, building metal-induced chirality for square-planar complexes still remains a big challenge, because their 2D planar molecular structures are usually superimposable on their mirror images. Herein, we report a straightforward and efficient way to achieve a novel kind of planar chirality by constructing 3D double-layer molecular structures. When the achiral ligand 1,3,4-oxadiazole-2-thiol (OXT) was used to bridge two square-planar complexes, a pair of racemic R/S planar-chiral binuclear Pt(II) complexes was obtained, which could be separated by chiral high-performance liquid chromatography (HPLC). Moreover, enantiopure R,R,R or S,S,S complexes could be prepared by the use of chiral (R)-/(S)-binaphthalene-derived OXT ligands in 99% diastereoselectivity without the use of chiral HPLC. The binaphthalene groups help to ensure good solubility and a smooth amorphous thin film morphology but have little effect on the photophysical properties. The resultant complexes display strong orange-red and near-infrared phosphorescence with quantum yields of up to 83.4% and can be applied as emitters in highly efficient solution-processed organic light-emitting diodes to achieve luminance, luminance efficiency, external quantum efficiency, and an asymmetry factor of up to 3.22 × 104 cd m-2, 28.7 cd A-1, 14.3%, and 2.0 × 10-3, respectively. With a comprehensive consideration of EL efficiency and the asymmetry factor, this is the best performance among Pt(II) complex based circularly polarized OLEDs. Therefore, this work provides a new and simple strategy to build planar chirality for chiroptical and circularly polarized luminescence applications.

Dispersion and Steric Effects on Enantio-/Diastereoselectivities in Synergistic Dual Transition-Metal Catalysis.

Comprehensive computational studies were carried out to explore the mechanisms of enantioselective Cu/Pd and stereodivergent Cu/Ir dual-catalytic syntheses of α,α-disubstituted α-amino acids (α-AAs). A chiral copper azomethine ylide undergoes facile α-allylation with racemic π-allylpalladium species or stereopure π-allyliridium complex to stereoconvergently or stereodivergently furnish single/double stereocenters, respectively. Stereoselectivity at the α-center is controlled by the facial selectivity of α-allylation with respect to the prochiral nucleophile. Despite apparently similar transition-state assemblies, computational models and distortion/interaction analyses disclose versatile modes of stereoinduction wherein the copper azomethine ylide species can face-selectively intercept metal-π-allyl intermediates utilizing attractive dispersion interactions and/or sterically caused distortions. Generation of the β-stereocenter in the Cu/Ir system relies on a stereospecifically generated allyliridium complex and electronically controlled branched-to-linear selectivity, while the dual Cu/Pd system yields a linear monochiral product due to steric factors and π-π stacking interactions. The studies demonstrate on a molecular level how ligand-encoded chiral information is transferred to the α-/β-sites of the resulting α-AAs and how the mode of regio-/stereoselection is altered by differences in transition-metal-stabilized coupling partners. To facilitate studies of stereoselective catalysis, a suite of analytical tools to extract controlling factors for asymmetric induction is demonstrated.

Hydrogen-Bonding Interactions Trigger Induction of Chirality via Formation of a Cyclic Dimer.

A rationalization for the chirality transfer mechanism in the supramolecular host-guest assemblies of an achiral Zn(II) porphyrin dimer (host) and a series of chiral diamines and diamino esters (substrates) via cyclic dimer formation has been reported for the first time. Stepwise formations of 2:2 host-guest cyclic dimers and 1:2 host-guest monomeric complexes have been observed via intermolecular assembling and disassembling processes. A large bisignate CD couplet was observed for the cyclic dimer, whereas the monomeric complexes exhibited negligible CD intensity. Crystallographic characterizations demonstrate that the strong intermolecular H bonding in cyclic dimers is responsible for their stability over the linear chain, which thereby display high-intensity bisignate CD couplets. In order to minimize the steric crowding within the host-guest assembly, the cyclic dimer switches its helicity toward the conformer having less steric hindrance. The cyclic scaffold is oriented according to the pre-existing chirality of the substrate in both the solid and solution phases: the substrates having R chirality display a negative CD couplet, whereas the substrates with S chirality display a positive couplet. Opposite signs for the CD couplets between R and S substrates suggest that the stereographic projection at the chiral centers solely dictates the overall helicity of the cyclic dimer. DFT studies further support the experimental observations.

The More the Slower: Self-Inhibition in Supramolecular Chirality Induction, Memory, Erasure, and Reversion

Self-inhibition has been observed widely in hierarchical biochemical processes but has yet to be demonstrated in pure molecular physical rather than chemical or biological processes. Herein, we report an unprecedented example of self-inhibition during the supramolecular chirality induction, memory, erasure, and inversion processes of pillar[5]arene (P[5]) derivatives. The addition of chiral alanine ethyl ester to bulky substituent-modified P[5]s led to time-dependent chirality induction due to the shift in the equilibrium of the SP and RP conformers P[5]. Intriguingly, more chiral inducers led to more intensive final chiroptical properties but lower chiral induction rates. Thus, the chiral inducer plays the role of both activator and inhibitor. Such self-inhibition essentially arises from kinetics manipulation of three tandem equilibria. Moreover, the chiroptical properties could be memorized by replacing the chiral inducer with an achiral competitive binder, and the chiroptical signal could be erased and reversed by an antipodal chiral inducer, which also showed the self-inhibition property.

Molecular Field Analysis Using Computational-Screening Data in Asymmetric N-Heterocyclic Carbene-Copper Catalysis toward Data-Driven In Silico Catalyst Optimization

Abstract A molecular-field-based regression analysis using computational screening data for N-heterocyclic carbene (NHC)-Cu-catalyzed asymmetric carbonyl additions of a silylboronate to aldehydes is reported. A computational screening was performed to collect enantioselectivity data (ΔΔG‡: energy differences between the transition states leading to each enantiomer) via transition-state (TS) calculations using density functional theory (DFT) methods. A molecular field analysis (MFA) was carried out using the obtained calculated ΔΔG‡ values and TS structures (30 samples in total). Important structural information for enantioselectivity extracted by the MFA was visualized on the TS structures, which provided insight into an asymmetric induction mechanism. Based on the obtained information, chiral NHC ligands were designed, which showed improved enantioselectivity in these carbonyl additions (designed ligands: up to 96% ee, initial training samples: up to 73% ee).

On the Synthesis of a Novel Chiral Phosphorodiamidic Acid Containing­ the α-Phenylethyl Moiety: Insights on its Conformation and Reactivity

AbstractA few years ago, the synthesis of chiral phosphoric acids supported on chiral BINOL frameworks was accomplished by T. Akiyama and M. Terada. Subsequent relevant applications demonstrated the importance of chiral phosphoric acids as privileged chiral inducers in asymmetric organocatalysis. In the present report, we discuss the development of novel chiral phosphorodiamidic acids derived from C 2-symmetric trans-1,2-diaminocyclohexane aliphatic frameworks. The preparation of the new chiral Brønsted acids, based on the intermediacy of a 1,3,2-diheterophospholan-2-oxide moiety, turned out to be challenging since several plausible synthetic methodologies proved to be ineffective. Furthermore, the five-membered heterocyclic moiety turned out to be easily hydrolyzed when exposed to nucleophilic alcohols or water. Complementary to the successful multistep synthesis reported here, it was possible to obtain crystals of the key precursor of the desired phosphorodiamidic acid, which proved suitable for X-ray diffraction analysis and hence to establish important conformational characteristics of the novel heterocycle.

Environmental modulation of chiral prolinamide catalysts for stereodivergent conjugate addition

Synthetic chiral catalysts generally rely on proximal functional groups or ligands for chiral induction. Enzymes often employ environmental chirality to achieve stereoselectivity. Environmentally controlled catalysis has benefits such as size and shape selectivity but is underexplored by chemists. We here report molecularly imprinted nanoparticles (MINPs) that utilized their environmental chirality to either augment or reverse the intrinsic selectivity of a chiral prolinamide cofactor. The latter ability allowed the catalyst to produce products otherwise disfavored in the conjugate addition of aldehyde to nitroalkene. The catalysis occurred in water at room temperature and afforded γ-nitroaldehydes with excellent yields (up to 94%) and ee (>90% in most cases). Up to 25:1 syn/anti and 1:6 syn/anti ratios were achieved through a combination of catalyst-derived and environmentally enabled selectivity. The high enantioselectivity of the MINP also made it possible for racemic catalysts to perform asymmetric catalysis, with up to 80% ee for the conjugate addition.

Chiral Dinuclear EuIII, TbIII, and YIII Complexes Supported by P‐Stereogenic Linear Tetraphosphine Tetraoxide

AbstractA P‐stereogenic linear tetraphosphine tetraoxide, (R,R)‐ or (S,S)‐dpmppm(=O)4, was synthesized to prepare C2 dinuclear M(hfa)3 complexes (M=Eu, Tb, Y) as the first example of lanthanide(III) complexes with P‐chiral multidentate phosphine oxides. The mononuclear M(hfa)3 complexes (M=Eu, Y) with a P‐chiral diphosphine dioxide, tpdpb(=O)2, were also prepared, and comparison of their photophysical properties for the EuIII complexes revealed that significant chiral induction from the P‐chiral centers arises on the achiral M(hfa)3 units through intramolecular π‐π stacking constraint in the dinuclear system.

Amplification of weak chiral inductions for excellent control over the helical orientation of discrete topologically chiral (M3L2) n polyhedra.

Superb control over the helical chirality of discrete (M3L2)n polyhedra (n = 2,4,8, M = CuI or AgI) created from the self-assembly of propeller-shaped ligands (L) equipped with chiral side chains is demonstrated here. Almost perfect chiral induction (>99 : 1) of the helical orientation of the framework was achieved for the largest (M3L2)8 cube with 48 small chiral side chains (diameter: ∼5 nm), while no or moderate chiral induction was observed for smaller polyhedra (n = 2, 4). Thus, amplification of the weak chiral inductions of each ligand unit is an efficient way to control the chirality of large discrete nanostructures with high structural complexity.

Asymmetric induction in quadruple-stranded europium(iii) helicates and circularly polarized luminescence

Chiral supramolecular lanthanide-helicates are regarded as promising chiroptical materials due to their combination of ground and excited state chirality and special luminescence properties from Ln3+, named circularly polarized luminescence (CPL). However, the sophisticated and costly asymmetric syntheses decelerate their research progress. Herein, a chiral induction strategy is employed to break the racemic equilibrium of lanthanide helicate by the formation of a compact ion pair. The synthesized chiral guanidine cation ((R/S)-HG) helps to effectively transfer chirality to anionic quadruple-stranded helicate by electrostatic, H bonds, and multiple C-H⋯F and N-H⋯F interactions. The diastereoselective control was confirmed by X-ray crystallography and CD and CPL spectroscopy, where (S)-HG prefers to bind a P (ΔΔ) helical enantiomer, in contrast a M helicate for (R)-HG. Additionally, the inconsistency of CD and CPL spectra in assessing the perturbation of a racemic equilibrium discloses their complementary advantages on monitoring molecular chirality. In the case of diastereomeric enrichment equilibrium, three pairs of helicates show high luminescence quantum yields of 42%-54%, and large |glum| with the values of 0.137-0.266. This work provides an effective strategy to synthesize excellent CPL materials based on racemic lanthanide helicate.