Asymmetric Substitution Research Articles

Catalytic asymmetric C2-nucleophilic substitutions of C3-substituted indoles with ortho-hydroxybenzyl alcohols

Catalytic asymmetric C2-nucleophilic substitutions of C3-substituted indoles such as tryptophols or tryptamines with ortho-hydroxybenzyl alcohols have been established, leading to the generation of triaryl methane products in generally high yields and excellent enantioselectivities.

Catalytic asymmetric substitution of ortho-hydroxybenzyl alcohols with tetronic acid-derived enamines: enantioselective synthesis of tetronic acid-derived diarylmethanes

The first catalytic asymmetric substitution of ortho-hydroxybenzyl alcohols with enamines has been established.

Kinetic Resolution of Allylic Alcohols by Palladium-Catalyzed Asymmetric Substitution

Kinetic Resolution of Allylic Alcohols by Palladium-Catalyzed Asymmetric Substitution

ChemInform Abstract: Kinetic Resolution of Racemic Allylic Alcohols by Catalytic Asymmetric Substitution of the OH Group with Monosubstituted Hydrazines.

A new strategy has been established for the kinetic resolution of racemic allylic alcohols through a palladium/sulfonyl-hydrazide-catalyzed asymmetric OH-substitution under mild conditions. In the presence of 1 mol % [Pd(allyl)Cl]2 , 4 mol % (S)-SegPhos, and 10 mol % 2,5-dichlorobenzenesulfonyl hydrazide, a range of racemic allylic alcohols were smoothly resolved with selectivity factors of more than 400 through an asymmetric allylic alkylation of monosubstituted hydrazines under air at room temperature. Importantly, this kinetic resolution process provided various allylic alcohols and allylic hydrazine derivatives with high enantiopurity.

Use of a Catalytic Chiral Leaving Group for Asymmetric Substitutions at sp3 -Hybridized Carbon Atoms: Kinetic Resolution of β-Amino Alcohols by p-Methoxybenzylation.

A catalytic strategy was developed for asymmetric substitution reactions at sp3 -hybridized carbon atoms by using a chiral alkylating agent generated in situ from trichloroacetimidate and a chiral phosphoric acid. The resulting chiral p-methoxybenzyl phosphate selectively reacts with β-amino alcohols rather than those without a β-NH functionality. The use of an electronically and sterically tuned chiral phosphoric acid enables the kinetic resolution of amino alcohols through p-methoxybenzylation with good enantioselectivity.

Use of a Catalytic Chiral Leaving Group for Asymmetric Substitutions at sp3‐Hybridized Carbon Atoms: Kinetic Resolution of β‐Amino Alcohols by p‐Methoxybenzylation

AbstractA catalytic strategy was developed for asymmetric substitution reactions at sp3‐hybridized carbon atoms by using a chiral alkylating agent generated in situ from trichloroacetimidate and a chiral phosphoric acid. The resulting chiral p‐methoxybenzyl phosphate selectively reacts with β‐amino alcohols rather than those without a β‐NH functionality. The use of an electronically and sterically tuned chiral phosphoric acid enables the kinetic resolution of amino alcohols through p‐methoxybenzylation with good enantioselectivity.

Toward High Efficiency Polymer Solar Cells: Influence of Local Chemical Environment and Morphology

The chemical structure of conjugated polymers plays an important role in determining their physical properties that, in turn, dictates their performance in photovoltaic devices. 5‐Fluoro‐2,1,3‐benzothiadiazole, an asymmetric unit, is incorporated into a thiophene‐based polymer backbone to generate a hole conducting polymers with controlled regioregularity. A high dipole moment is seen in regioregular polymers, which have a tighter interchain stacking that promotes the formation of a morphology in bulk heterojunction blends with improved power conversion efficiencies. Aliphatic side chain substitution is systematically varied to understand the influence of side chain length and symmetry on the morphology and resultant performance. This side chain modification is found to influence crystal orientation and the phase separated morphology. Using the asymmetric side chain substitution with regioregularity of the main chain, an optimized power conversion efficiency of 9.06% is achieved, with an open circuit voltage of 0.72 V, a short circuit current of 19.63 mA cm−2, and a fill factor over 65%. These results demonstrate that the local chemical environment can dramatically influence the physical properties of the resultant material.

Electrochemistry and STM Observation of a Copper Complex-Based Molecular Rotor on Gold

Molecular rotors demonstrate that switching and mechanical work can be achieved at the nanoscale. The development of a system whereby the switching behavior is controllable at room temperature is one of the ultimate goals in this research field. Further research in this area could lead to the development of methods of detecting or visualizing the motion of individual molecules, which would greatly aid the functionality of future single molecular machines and memory devices. Our group has recently developed a pyridylpyrimidine-ligated copper(I) complex system that acts as a molecular switch through the redox-driven rotation of a coordinated pyrimidine ring (Figure 1).1 Asymmetric substitution at the 4-position of the pyrimidine ring leads to the two switching isomers, in which different degrees of steric congestion result in distinct oxidation potentials. The rotation of this system can be driven by temperature and light, and furthermore, the motion can be detected as various kinds of outputs; for example, changes of rest potential, magnetic and optical properties. Note that it is the correlation between redox potential and structure that enables these functionalities within a simple and small molecular design. In this research, a new molecular switch, a copper complex (1•PF6 ), was synthesized. Cyclic voltammograms of 1•PF6 in solution taken at room temperature had two redox couples. Based on the electrochemistry of Cu complexes, these signals were assigned to the redox reactions of the o- and i-isomer from the negative to the positive potential. This complex was immobilized on the Au surface by immersing an Au-coated mica substrate in a CH2Cl2 solution of 1•PF6 ; the modified substrate is designated as SAM-1. Cyclic voltammetry of SAM-1 at room temperature shows two reversible copper(II/I) redox waves at potentials similar to those of 1•PF6 in solution. From the deconvolution of peak areas, the ratio of the two isomers functionalized on the Au surface was calculated. Different scan rates measurements of oxidation waves suggested that the ratio of the isomers is constant and does not deviate from the equilibrium molar ratio (i : o = 8 : 2). We next carried out scanning tunneling microscopy to observe the isomerization behavior of individual molecules. A mixed self-assembled monolayer (SAM) of 1•PF6 and 1-hexanethiol (mSAM-1) was used for STM observation at room temperature. The brightness of spots are measured as the apparent height. It was found that apparent heights of the complex molecules varied with time as they switched between the two states. Aggregated apparent height data show two Gaussian components. Least squares fitting of the two components indicates that 1 has two conformations which have an area ratio of 8 : 2. This ratio seems consistent with the Cu(I) equilibrium ratio of the i- and o-isomers (i : o = 8 : 2), which suggests a successful observation of the switching behavior of individual molecules. Reference M. Nishikawa, S. Kume, H. Nishihara, Phys. Chem. Chem. Phys. 2013, 15, 10549-10565. Figure 1

Kinetic Resolution of Racemic Allylic Alcohols by Catalytic Asymmetric Substitution of the OH Group with Monosubstituted Hydrazines.

A new strategy has been established for the kinetic resolution of racemic allylic alcohols through a palladium/sulfonyl-hydrazide-catalyzed asymmetric OH-substitution under mild conditions. In the presence of 1 mol % [Pd(allyl)Cl]2 , 4 mol % (S)-SegPhos, and 10 mol % 2,5-dichlorobenzenesulfonyl hydrazide, a range of racemic allylic alcohols were smoothly resolved with selectivity factors of more than 400 through an asymmetric allylic alkylation of monosubstituted hydrazines under air at room temperature. Importantly, this kinetic resolution process provided various allylic alcohols and allylic hydrazine derivatives with high enantiopurity.

ChemInform Abstract: Catalytic Asymmetric Cascade Dearomatization of Tryptamines with Indol‐3‐ylmethanols: Diastereo‐ and Enantioselective Synthesis of Structurally Complex Indole Derivatives.

A chiral phosphoric acid-catalyzed asymmetric cascade dearomatization reaction of tryptamines with indol-3-ylmethanols has been established. This not only realized the first catalytic asymmetric cascade substitution of indol-3-ylmethanols, but also provided an efficient and stereoselective method (99% yield, >95:5 dr, 95:5 er) for constructing complex pyrroloindoline-based skeletons with three contiguous stereogenic centers, two of which were all-carbon quaternary centers.

Changing Trends in U.S. Alcohol Demand

This study uses the Fourier globally flexible functional form and shows that elasticities of substitution for beer, wine and spirits vary over time. Own-price elasticities show that demand for alcohol is inelastic. Estimates of cross-price elasticities show much variation over time between spirits, wine and beer. Cross-price elasticities between beer and wine are generally elastic. Evidence of asymmetric substitution involving beer with wine or spirits suggests alcohol expenditure depends on which product undergoes a price change, which is typically not the case for spirits and wine. Changes in the demand for alcohol over time have important implications for the effectiveness of policy aimed at reducing externalities associated with heavy drinking. Morishima elasticities of substitution have different magnitudes compared to the cross-price elasticities but similar trends.

Stockout-Based Substitution and Inventory Planning in Textbook Retailing

We demonstrate the value of utility-based choice models to estimate demand and plan inventory for new and used textbooks in the presence of consumer choice and stockout-based substitution at a university textbook retailer. Demand information is censored, the exact time of stockout is not observed, and the short selling season often does not allow for replenishment. Using data for 26,749 book titles from 2007 to 2011 and a simulation experiment calibrated on real data, we show that an attribute-based choice model generates accurate demand estimates (mean absolute percentage error less than 1%) even when nearly 90% of the textbooks in the fit sample experience stockout. This performance is driven by the heterogeneity of product attributes and is robust to the occurrence of product returns. We implement this model at the bookstore in a controlled field experiment and obtain over 10% increase in profit. The results show that accounting for asymmetric and stockout-based substitution in demand estimation and inventory planning enables us to make systematic corrections in inventory mix and inventory level compared to the existing process.

Bridging Chiral Calix[4]arenes: Description, Optical Resolution, and Absolute Configuration Determination

AbstractA new chiral calix[4]arene constructed from asymmetric substitution on bridging methylenes, phenyl rings, and (or) oxygen atoms was tentatively named as “bridging chiral” calix[4]arene that have point chirality on its substituted bridging methylene. A new approach to enantiopure bridging chiral calix[4]arenes through optical resolution is presented for the first time. As a result, a pair of enantiopure bridging chiral calix[4]arene carboxylic acids monobridge‐substituted with an equatorial N,N′‐dimethylformamidyl group (4a and 4b) were easily prepared by the optical resolution of their racemate with chiral auxiliary (S)‐Binol. The absolute configurations of the enantiomers were determined by X‐ray crystallographic analysis.

Aggregation-induced emission type thermally activated delayed fluorescent materials for high efficiency in non-doped organic light-emitting diodes

Aggregation-induced emission (AIE) type thermally activated delayed fluorescent (TADF) emitters were developed by asymmetric substitution of donor moieties to a diphenylsulfone acceptor. The AIE properties of the TADF emitters increased the quantum efficiency of the non-doped TADF devices and asymmetric substitution was more effective than symmetric substitution to enhance the quantum efficiency of the non-doped devices.

Catalytic Asymmetric Cascade Dearomatization of Tryptamines with Indol-3-ylmethanols: Diastereo- and Enantioselective Synthesis of Structurally Complex Indole Derivatives

A chiral phosphoric acid-catalyzed asymmetric cascade dearomatization reaction of tryptamines with indol-3-ylmethanols has been established. This not only realized the first catalytic asymmetric cascade substitution of indol-3-ylmethanols, but also provided an efficient and stereoselective method (99% yield, >95:5 dr, 95:5 er) for constructing complex pyrroloindoline-based skeletons with three contiguous stereogenic centers, two of which were all-carbon quaternary centers.

ChemInform Abstract: Copper‐Catalyzed Intermolecular Asymmetric Propargylic Dearomatization of Indoles.

The first copper-catalyzed intermolecular dearomatization of indoles by an asymmetric propargylic substitution reaction was developed. This method provides a highly efficient synthesis of versatile furoindoline and pyrroloindoline derivatives containing a quaternary carbon stereogenic center and a terminal alkyne moiety with up to 86 % yield and 98 % ee.

Copper‐Catalyzed Intermolecular Asymmetric Propargylic Dearomatization of Indoles

AbstractThe first copper‐catalyzed intermolecular dearomatization of indoles by an asymmetric propargylic substitution reaction was developed. This method provides a highly efficient synthesis of versatile furoindoline and pyrroloindoline derivatives containing a quaternary carbon stereogenic center and a terminal alkyne moiety with up to 86 % yield and 98 % ee.

Copper-catalyzed intermolecular asymmetric propargylic dearomatization of indoles.

The first copper-catalyzed intermolecular dearomatization of indoles by an asymmetric propargylic substitution reaction was developed. This method provides a highly efficient synthesis of versatile furoindoline and pyrroloindoline derivatives containing a quaternary carbon stereogenic center and a terminal alkyne moiety with up to 86 % yield and 98 % ee.

A mechanistic study of the participation of azomethine ylides and carbonyl ylides in [3+2] cycloaddition reactions

The participation of azomethine ylides (AYs) and carbonyl ylides (CYs) in [3+2] cycloaddition (32CA) reactions has been analysed at the DFT B3LYP/6-31G(d) level. The asymmetric substitution breaks the pseudodiradical character of the simplest three-atom-components (TACs), modifying their electrophilic and nucleophilic behaviours. These TACs react quickly towards electrophilic nitroethylene. However, while the reaction with AY takes place via a zw-type mechanism, the reaction with CY appears to take place via a pr-type mechanism. A different behaviour is found in the reactivity towards the nucleophilic methyl vinyl ether. While AY presents a high activation energy, CY presents a high reactivity via a pr-type mechanism. These reactions are completely regioselective, displaying exo stereoselectivity. The present study makes it possible to establish that the substitution provokes a different reactivity pattern in these TACs; while in CYs does not substantially modify their pr-type reactivity, AYs only participate in zw-type 32CA reactions towards electrophilic ethylenes.

The Jahn-Teller effect in the presence of partial isotopic substitution: the B̃(1)E'' state of NH2D and NHD2.

Rotationally resolved resonance enhanced multiphoton ionisation spectra of the B̃(1)E'' state of NH2D are presented and analysed. The analysis indicates a small (34.9 cm(-1)) lifting of the vibronic degeneracy of the zero point level, approximately equal in sign but opposite in magnitude to the splitting observed in NHD2 in previous work. This observation is consistent with previous measurements on systems with partial isotopic substitution subject to a mild Jahn-Teller effect. A model is developed to calculate the splitting induced by asymmetric isotopic substitution of a degenerate electronic state, based on a harmonic force field with linear and quadratic Jahn-Teller terms added. The force field is developed in internal co-ordinates to allow the same parameters to be used to calculate the pattern of vibronic levels for all four isotopologues. The lifting of the degeneracy of the zero point level on asymmetric substitution comes from the quadratic Jahn-Teller effect; the linear term does not lift the degeneracy.