Steric and Electronic Effects on the Configurational Stability of Residual Chiral Phosphorus‐Centered Three‐Bladed Propellers: Tris‐aryl Phosphane Oxides

A series of tris‐aryl phosphane oxides existing as residual enantiomers or diastereoisomers with substituents on the aryl rings differing in size and electronic properties were synthesized and characterized. Their electronic properties were evaluated on the basis of their electrochemical oxidation and reduction potentials together with those of the corresponding “blade bromides” (i.e., the naphthalene derivatives displaying the same substitution pattern of the tris‐naphthyl phosphane oxide blades, with a bromo substituent where the phosphorus atom is located) determined by CV. The residual stereoisomeric phosphane oxides were isolated in a stereochemically pure state and were found to be highly configurationally stable at room temperature (stereoisomerization barriers of about 27 kcal mol^?1). The chiroptical properties of the residual stereoisomers and the assignments of absolute configuration are discussed. The configurational stability of residual tris‐aryl phosphane oxides was found to be scarcely influenced by the electronic properties of the substituents present on the aromatic rings constituting the blades, while steric effects play the most relevant role. Detailed theoretical calculations are in agreement with the experimental results and also contribute to a rational interpretation of the stereodynamics of these systems.     

Helical Chiral N-Heterocyclic Carbene Ligands in Enantioselective Gold Catalysis

The first chiral helicene-NHC gold(I) complexes efficient in enantioselective catalysis were prepared. The L-shaped chiral ligand is composed of an imidazo[1,5-a]pyridin-3-ylidene (IPy) scaffold laterally substituted by a configurationally stable [5]-helicenoid unit. The chiral information was introduced in a key post-functionalization step of a NHC-gold(I) complex bearing a symmetrical anionic fluoreno[5]helicene substituent, leading to a racemic mixture of complexes featuring three correlated elements of chirality, namely central, axial and helical chirality. After HPLC enantiomeric resolution, X-ray crystallography and theoretical calculations enabled structural and stereochemical characterization of these configurationally stable NHC-gold(I) complexes. The high potential in asymmetric catalysis is demonstrated in the benchmark cycloisomerization of N-tethered 1,6-enynes with up to 95 : 5 er.     

Chirality in the Absence of Rigid Stereogenic Elements: The Absolute Configuration of Residual Enantiomers of C3‐Symmetric Propellers

Two new tris(aryl)phosphane oxides existing as configurationally stable residual enantiomers have been synthesised and their racemates resolved by semipreparative HPLC on a chiral stationary phase (CSP HPLC). One of them, recognised as a conglomerate, could be resolved by fractional crystallisation at a preparative scale level. In this case, the absolute configuration of the propeller‐shaped molecule was determined by anomalous X‐ray scattering. The problem of the correlative assignment of the absolute configuration to all known C₃‐symmetric three‐bladed propeller‐shaped molecules existing as stable residual enantiomers is discussed. The configurational stability of the new chiral phosphane oxides and of the corresponding phosphanes was evaluated by CD signal decay kinetics and dynamic ¹H NMR spectroscopy. The racemisation barriers in phosphanes were found about 10 kcal mol^?1 lower than those found for the corresponding oxides, though geometry and inter‐ring gearing would be very similar in the two series. Configurational stability of residual tris(aryl)phosphanes was found to be influenced by the electronic availability of the phosphorus centre, as evaluated by electrochemical CV experiments.     

Chirality in the Absence of Rigid Stereogenic Elements: The Design of Configurationally Stable C3‐Symmetric Propellers

Residual stereoisomerism is a form of stereoisomerism scarcely considered so far for applicative purposes, though extremely interesting, since the production of stereoisomers does not involve classical rigid stereogenic elements. In three‐bladed propeller‐shaped molecules, a preferred stereomerization mechanism, related to the correlated rotation of the rings, allows the free interconversion of stereoisomers inside separated sets (the residual stereoisomers) that can interconvert through higher energy pathways. In light of possible future applications as chiral ligands for transition metals in stereoselective processes, some C₃‐symmetric phosphorus‐centered propellers, which could exist as residual enantiomers, are synthesized and the possibility of resolving their racemates into residual antipodes is explored. While the tris(aryl)methanes are configurationally stable at room temperature, only selected tris(aryl)phosphane oxides display a configurational stability high enough to allow resolution by HPLC on a chiral stationary phase (CSP HPLC) at a semipreparative level at room temperature. Stability was evaluated through different techniques (circular dichroism (CD) signal decay, dynamic CSP HPLC (CSP DHPLC), dynamic NMR analysis (DNMR)) and the results compared and discussed. Phosphanes were found much less stable than the corresponding phosphane oxides, for which preliminary calculations suggest that the three‐ring‐flip enantiomerization mechanism (M₀) would be easier than phosphorus pyramidal inversion. The parameters affecting the configurational stability of the residual enantiomers of C₃‐symmetric propellers are discussed.     

A stereospecific synthesis of oxazolinyloxiranes

Lithiooxiranes 3a and 3b, generated by deprotonation of oxiranes 2a and 2b with s-BuLi at -100 degrees C in Et(2)O, were found to be chemically very stable. trans-Lithiooxirane 3a was also configurationally stable and reacted stereospecifically with electrophiles to give 4a--k. In contrast, cis-lithiooxirane 3b was found to be configurationally much less stable and reacted with electrophiles affording mixtures of diastereomers 4, 7, and 8. After only a very short reaction time, 3b too reacted with electrophiles highly stereospecifically. Deprotonation--deuteration and deprotonation--alkylation of chiral oxazolinyloxiranes 12a and 12b to give oxiranes 12c and 12d were also examined. Semiempirical and ab initio calculations were carried out in an effort to explain the observed stereochemistry.     

Layered lanthanide molybdate pillared by chiral [lambda-Mo2O4EDTA]2-

Hydrothermal reactions of Na2[Mo2O4EDTA].5H2O and LnCl3.6H2O produce the chiral layered lanthanide molybdate oxides pillared by the chiral cluster ligand, [Ln(H2O)MoO4]2[lambda-Mo2O4EDTA] (Ln = Gd, 1; Eu, 2; Tb, 3; Y, 4). The tetradentate molybdate bridges Ln3+ to form a square grid structure, which is pillared by the chiral cluster ligand, [lambda-Mo2O4EDTA]2-, into a 3-D chiral framework structure. Strong VCD (vibrational circular dichroism) signals confirm the chirality of the bulk oxide materials. These bimetallic oxide materials are of highly thermal stability. The magnetic interactions between the Ln3+ ions in 1 and 3 are weak antiferromagnetic.     

Air-stable P-stereogenic secondary phosphine oxides as chiral monodentate ligands for asymmetric catalytic carboncarbon bond formation

P-Stereogenic secondary phosphine oxides are configurationally stable in the presence of metal ions both in solution and in the solid state. They have the potential to serve as chiral monodentate phosphorus ligands for asymmetric catalysis. In the asymmetric allylic alkylation of 1,3-diphenylprop-2-enyl acetate, ca. 80% ee was achieved using (R_p)-tert-butylphenylphosphine oxide.     

Homochiral helices of oligonaphthalenes inducing opposite-handed cholesteric phases

The helical structure of the chiral nematic phases (cholesterics) obtained by doping nematic solvents with chiral non-racemic compounds is a macroscopic proof of the solute chirality. Oligonaphthalene (tetra-, hexa-, octa-) derivatives linked at the 1,4-positions have been used as chiral dopants: When the chirality axes are configurationally homogeneous (that is, all-S), the molecular structures correspond to right-handed helices. Yet, we have found series of derivatives with the surprising property that the handedness of the induced cholesteric phase alternates from positive to negative and to positive again, on passing from tetra- to hexa- and to octanaphthalene. A comparison with oligonapthalene derivatives, which do not exhibit this twisting ability, points to the importance of the substitution pattern. Both the possibility of inducing oppositely-handed cholesteric phases by homochiral helices of different length, and the role played of substituents, are confirmed by calculations performed with the surface chirality model.     

Laser-operated chiral molecular switch: quantum simulations for the controlled transformation between achiral and chiral atropisomers

We report quantum dynamical simulations for the laser controlled isomerization of 1-(2-cis-fluoroethenyl)-2-fluorobenzene based on one-dimensional electronic ground and excited state potentials obtained from (TD)DFT calculations. 1-(2-cis-fluoroethenyl)-2-fluorobenzene supports two chiral and one achiral atropisomers, the latter being the most stable isomer at room temperature. Using a linearly polarized IR laser pulse the molecule is excited to an internal rotation around its chiral axis, i.e. around the C-C single bond between phenyl ring and ethenyl group, changing the molecular chirality. A second linearly polarized laser pulse stops the torsion to prepare the desired enantiomeric form of the molecule. This laser control allows the selective switching between the achiral and either the left- or right-handed form of the molecule. Once the chirality is "switched on" linearly polarized UV laser pulses allow the selective change of the chirality using the electronic excited state as intermediate state.     

Spectroscopic investigation on chirality transfer in additive-driven self-assembly of block polymers

Chiral supramolecules prepared by the additive-driven self-assembly of block copolymers provide a facile method to construct helical nanostructures. In this study, we investigated the chiral transfer from chiral tartaric acid to poly(styrene)-b-poly(ethylene oxide) using small-angle X-ray scattering, transmission electron microscopy, circular dichroism, and vibrational circular dichroism. The results showed that the chirality was transferred to both the segments of block copolymer irrespective of the interaction with the chiral additives and formation of helical phase structure. However, the chirality transfer was carried out using different methods: for poly(ethylene oxide) segments, the chirality transfer was carried out via direct hydrogen bond formation; for polystyrene segments, the chirality transfer was carried out via the cooperative motion of block copolymers during the thermal annealing.     

Axially Chiral Dibenzazepinones by a Palladium(0)‐Catalyzed Atropo‐enantioselective C−H Arylation

Atropo‐enantioselective C?H functionalization reactions are largely limited to the dynamic kinetic resolution of biaryl substrates through the introduction of steric bulk proximal to the axis of chirality. Reported herein is a highly atropo‐enantioselective palladium(0)‐catalyzed methodology that forges the axis of chirality during the C?H functionalization process, enabling the synthesis of axially chiral dibenzazepinones. Computational investigations support experimentally determined racemization barriers, while also indicating C?H functionalization proceeds by an enantio‐determining CMD to yield configurationally stable eight‐membered palladacycles.     

Asymmetric Catalysis by Architectural and Functional Molecular Engineering: Practical Chemo- and Stereoselective Hydrogenation of Ketones

Hydrogenation is a core technology in chemical synthesis. High rates and selectivities are attainable only by the coordination of structurally well-designed catalysts and suitable reaction conditions. The newly devised [RuCl(2)(phosphane)(2)(1,2-diamine)] complexes are excellent precatalysts for homogeneous hydrogenation of simple ketones which lack any functionality capable of interacting with the metal center. This catalyst system allows for the preferential reduction of a C=O function over a coexisting C=C linkage in a 2-propanol solution containing an alkaline base. The hydrogenation tolerates many substituents including F, Cl, Br, I, CF(3), OCH(3), OCH(2)C(6)H(5), COOCH(CH(3))(2), NO(2), NH(2), and NRCOR as well as various electron-rich and -deficient heterocycles. Furthermore, stereoselectivity is easily controlled by the electronic and steric properties (bulkiness and chirality) of the ligands as well as the reaction conditions. Diastereoselectivities observed in the catalytic hydrogenation of cyclic and acyclic ketones with the standard triphenylphosphane/ethylenediamine combination compare well with the best conventional hydride reductions. The use of appropriate chiral diphosphanes, particularly BINAP compounds, and chiral diamines results in rapid and productive asymmetric hydrogenation of a range of aromatic and heteroaromatic ketones and gives a consistently high enantioselectivity. Certain amino and alkoxy ketones can be used as substrates. Cyclic and acyclic alpha,beta-unsaturated ketones can be converted into chiral allyl alcohols of high enantiomeric purity. Hydrogenation of configurationally labile ketones allows for the dynamic kinetic discrimination of diastereomers, epimers, and enantiomers. This new method shows promise in the practical synthesis of a wide variety of chiral alcohols from achiral and chiral ketone substrates. Its versatility is manifested by the asymmetric synthesis of some biologically significant chiral compounds. The high rate and carbonyl selectivity are based on nonclassical metal-ligand bifunctional catalysis involving an 18-electron amino ruthenium hydride complex and a 16-electron amido ruthenium species.     

Mechanism of diastereoisomer-induced chirality of BiOBr

Chiral molecule-driven asymmetric structures are known to be elusive because of the intriguing chirality transfer from chiral molecules to achiral species. Here, we found that the chiral assembly of BiOBr is independent of the chirality of the organic molecular inducer but dependent on geometric structural matching between the inducer and inorganic species. Diastereoisomeric sugar alcohols (DSAs) with identical numbers of carbon chiral centers and functional groups but with different R/S configurations and optical activities (OAs) were chosen as symmetry-breaking agents for inducing chiral mesostructured BiOBr films (CMBFs) under hydrothermal conditions. Multiple levels of chirality with different handedness were identified in the CMBFs. Density functional theory (DFT) calculations and molecular dynamics (MD) simulations suggest that asymmetric defects in the Br–Bi tetragonal cone caused by physically adsorbed DSAs on the surfaces of the BiOBr crystals are the geometric basis for triggering the chiral twist in the BiOBr monolayer. Our findings provide new insights for understanding the origin of chirality and the chiral transfer mechanism underlying the assembly of achiral species.

The chirality transfer is dependent on geometrical matching between the chiral inducer and inorganic species.     

X-ray structures of the tris(2,4-xylyl)phosphane and its trisulfonated derivative: Molecular architecture of a water-soluble sulfonated phosphane with propeller chirality

The structure of tris(2,4-xylyl)phosphane (1) is reported and supramolecular assembly of gua⁺ salt of tris(2,4-dimethyl-5-sulfonatophenyl)phosphane co-crystal with guanidine chloride (2) is analyzed in detail. Weaving hydrogen bond ribbons with polar and apolar stabilizing pillars as well as stacking interaction of phenyl rings resulting sixfold phenyl embraces interpenetrating with the polar networks were found. Both compounds are racemate, show propeller chirality and 2 crystallizes in non-centrosymmetric space group (C₃ symmetry) with the ortho-methyl groups outside of the molecular cone. According to the DFT calculations on the anion of 2, the high barrier of concerted ring rotation opens the possibility of resolving the enantiomers through hydrogen bonds to chiral donors.     

A molecular dynamics study of chirality transfer: The impact of a chiral solute on an achiral solvent

A solvation shell may adapt to the presence of a chiral solute by becoming chiral. The extent of this chirality transfer and its dependence on the solute and solvent characteristics are explored in this article. Molecular dynamics simulations of solvated chiral analytes form the basis of the analysis. The chirality induced in the solvent is assessed based on a series of related chirality indexes originally proposed by Osipov [M. A. Osipov et al., Mol. Phys. 84, 1193 (1995)]. Two solvents are considered: Ethanol and benzyl alcohol. Ethanol provides insight into chirality transfer when the solvent interacts with the solute primarily by a hydrogen bond. Several ethanol models have been considered starting with a nonpolarizable model, progressing to a fluctuating charge model, and finally, to a fully polarizable model. This progression provides some insights into the importance of solvent polarizability in the transfer of chirality. Benzyl alcohol, by virtue of the aromatic ring, increases the number of potential solvent-solute interactions. Thus, with these two solvents, the issue of compatibility between the solvent and solute is also considered. The solvation of three chiral solutes is examined: Styrene oxide, acenaphthenol, and n-(1-(4-bromophenyl)ethyl)pivalamide (PAMD). All three solutes have the possibility of hydrogen bonding with the solvent, the last two may also form ring-ring interactions, and the last also has multiple hydrogen bonding sites. For PAMD, the impact of conformational averaging is examined by comparing the chirality transfer about rigid and flexible solutes.     

TDDFT studies on chiral organophosphonate substituted divacant Keggin-type polyoxotungstate: diplex multistep-redox-triggered chiroptical and NLO switch

We theoretically investigate a novel switching phenomenon based on the divacant Keggin-type polyoxotungstate bearing chiral organophosphonate [{NH(2)CH(CH(3))PO}(2)(γ-SiW(10)O(36))](4-), that is the synchronous chiroptical and nonlinear optical (NLO) switch triggered by redox. The ECD calculations on the Boltzmann weighted conformations of the three oxidation states of this chiral polyoxometalate (POM) clearly present a chiroptical switching process. The electronic transition and the bond-length alternation studies show that the chirality transfer from chiral carbon atom to POM cage increases as the polyanion is reduced. Simultaneously, the static first hyperpolarizability of studied chiral POM quadrupled from the oxidized state to the 1e-reduced state, and is further doubled to the 2e-reduced state, which is mainly due to the increasing electronic-dipole-allowed d-d charge transfer transitions in the POM cage. This work firstly reproduces the ECD spectrum of chiral POM with high accuracy and proves the possibility for confirming the molecular conformations of flexible chiral POMs in solution by the aid of ECD calculations. Most importantly, a sensitive diplex switch based on a chiral POM is predicted in theory, which may aid the design of novel POM-based switches.     

Convergent and stereospecific synthesis of molecules containing alpha-functionalized guanidiniums via alpha-guanidino acids

To introduce chirality and functional groups adjacent to guanidiniums to modulate specificity and affinity in recognition, N,N'-bis(Boc)-alpha-guanidino acids were synthesized from alpha-amino acid methyl esters. Protected alpha-guanidino acids coupled to cyclohexylamine and trans-1,4-diaminocyclohexane in good yield and with retention of stereochemistry. Boc deprotection was conducted under mild acidic conditions (0.5 M HCl/EtOAc) to minimize epimerization. The deprotected guanidinium is configurationally stable under more acidic conditions. This approach represents a practical, convergent, stereospecific methodology to introduce chiral alpha-substituted guanidinium groups into molecules.     

From Axial Chirality to Central Chiralities: Pinacol Cyclization of 2,2′-Biaryldicarbaldehyde to trans-9,10-Dihydrophenanthrene-9,10-diol

Two salient features —the stereoselectivity to give only the trans-diol, and the stereospecificity to transmit the axial chirality (in case the starting biphenyl is configurationally stable) onto two stereogenic centers of the product—characterize the pinacol cyclization of 2,2′-biaryldicarbaldehydes (see reaction). The accessibility of trans-9,10-dihydrophenanthrene-9,10-diols provides the new enantiopure C₂-symmetric diol 1 , which shows potential utility in asymmetric synthesis.     

Electron-induced switching of the supramolecular chirality of optically active polythiophene aggregates

A chiral regioregular polythiophene (PT), poly[3-[4-((R)-4-ethyl-2-oxazolin-2-yl)phenyl]thiophene] (poly-1), forms chiral aggregates which exhibit a unique induced circular dichroism (ICD) in the pi-pi transition region derived from the supramolecular chirality in the presence of various poor solvents or metal salts in chloroform. We report here that the chirality of such supramolecular aggregates can be switched ("on" and "off") through electron transfer. We have found that upon the addition of copper(II) trifluoromethanesulfonate [Cu(OTf)(2)] to the chiral aggregates of poly-1 in a chloroform-acetonitrile mixture, the ICD disappears because of the oxidative doping of the poly-1 main chain, while a further addition of amines such as triethylenetetramine (TETA) induces undoping of the poly-1 which results in the reappearance of the ICDs. Therefore, the supramolecular chirality of the poly-1 assemblies was reversibly controlled by the addition or removal of an electron from the poly-1 main chain. This may be the first example of a reversible supramolecular chirality switch on chiral PT aggregates. We investigated the mechanism of the chirality switch through the doping and undoping process on the polymer main chain by means of absorption and CD spectroscopies, ESR, cyclic voltammetry, X-ray diffraction, and AFM measurements.     

Chiral molecular nanosilicas

Molecular nanoparticles including polyoxometalates, proteins, fullerenes and polyhedral oligosiloxane (POSS) are nanosized objects with atomic precision, among which POSS derivatives are the smallest nanosilicas. Incorporation of molecular nanoparticles into chiral aggregates either by chiral matrices or self-assembly allows for the transfer of supramolecular chirality, yet the construction of intrinsic chirality with atomic precision in discrete molecules remains a great challenge. In this work, we present a molecular folding strategy to construct giant POSS molecules with inherent chirality. Ferrocenyl diamino acids are conjugated by two or four POSS segments. Hydrogen bonding-driven folding of diamino acid arms into parallel β-sheets facilitates the chirality transfer from amino acids to ferrocene and POSS respectively, disregarding the flexible alkyl spacers. Single crystal X-ray structures, density functional theory (DFT) calculations, circular dichroism and vibrational circular dichroism spectroscopy clearly verify the preferential formation of one enantiomer containing chiral molecular nanosilicas. The chiral orientation and chiroptical properties of POSS show pronounced dependence on the substituents of α-amino acids, affording an alternative way to control the folding behavior and POSS chirality in addition to the absolute configuration of amino acids. Through the kinetic nanoprecipitation protocol, one-dimensional aggregation enables chirality transfer from the molecular scale to the micrometer scale, self-assembling into helices in accordance with the packing propensity of POSS in a crystal phase. This work, by illustrating the construction of chiral molecular nanosilicas, paves a new way to obtain discrete chiral molecular nanoparticles for potential chiroptical applications.

A molecular folding strategy is developed to construct ferrocenyl diamino acid conjugated polyhedral oligosiloxane molecules. Hydrogen bonding-driven folding facilitates the chirality transfer from the molecular scale to the micrometer scale.