Origins of Optical Activity in an Oxo-Helicene: Experimental and Computational Studies.

Helicenes are known to provide extremely strong optical activity. Prediction of the properties of helicenes may facilitate their design and synthesis for analytical or materials sciences. On a model 7,12,17-trioxa[11]helicene molecule, experimental results from multiple spectroscopic techniques are analyzed on the basis of density functional theory (DFT) simulations to test computational methodology and analyze the origins of chirality. Infrared (IR), vibrational circular dichroism (VCD), electronic circular dichroism (ECD), magnetic circular dichroism (MCD), and Raman optical activity (ROA, computations only) spectra are compared. Large dissymmetry factors are predicted both for vibrational (ROA/Raman ∼ VCD/IR ∼ 10-3) and electronic (ECD/Abs ∼10-2) optical activity, which could be verified experimentally except for ROA. Largest VCD signals come from a strong vibrational coupling of the C-H in-plane and out-of-plane bending modes in stacked helicene rings. The sum-over-states (SOS) approach appeared convenient for simulation of MCD spectra. Our results demonstrated that selected computational methods can be successfully used for reliable modeling of spectral and chiroptical properties of large helicenes. In particular, they can be used for guiding rational design of strongly chiral chromophores.

Transition from Homochiral Clusters to Racemate Monolayers during 2D Crystallization of Trioxa[11]helicene on Ag(100).

The front cover artwork is provided by Prof. Ernst from Empa. The image shows determination of the sense of helicity of trioxa[11]helicene enantiomers with an atomic force microscope, which allows discrimination between homo- and heterochiral 2D self-assembly. Read the full text of the Article at 10.1002/cphc.202000853.

Transition from Homochiral Clusters to Racemate Monolayers during 2D Crystallization of Trioxa[11]helicene on Ag(100).

The phenomenon of chiral crystallization into homochiral crystals is known for more than 170 years, yet it is still poorly understood. Studying crystallization on surfaces under well-defined condition seems a promising approach towards better understanding the intermolecular chiral recognition mechanisms during nucleation and growth. The two-dimensional aggregation of racemic trioxaundecahelicene on the single crystalline silver(100) surface has been investigated with scanning tunneling microscopy and with non-contact atomic force microscopy, as well as molecular modeling simulations. A transition from homochiral cluster motifs to heterochiral assembly into large islands with increasing coverage is observed. Force field modelling confirms higher stability of heterochiral arrangements from twelve molecules on. Results are discussed with respect to previous findings for the all-carbon heptahelicene on the same surface.

Applications of chiral naphthyloxycyclohexanols in deracemization of α-substituted carboxylic acids by dynamic thermodynamic resolution.

Two derivatives of trans-2-naphthyloxycyclohexanol were synthesized, their enantiomers were separated by enzyme mediated kinetic resolution and their absolute configuration was established by synthesizing their diastereomers with esters of known chiral description. Chiral alcohols were then used as chiral auxiliaries for the preparation of esters by coupling with racemic α-halo acids. During the coupling reactions with DCC and a suitable base, an efficient dynamic thermodynamic resolution was observed and the products were isolated in high diastereomeric purity. The effect of several parameters on the reaction was studied and the absolute configuration of a newly created chiral centre was established by single crystal X-ray analysis; the correlation of the structure of chiral auxiliary and diastereoselectivity was investigated. The observed diastereoselectivity was in accordance with the relative energy profile of the products. The chirally pure α-halo acid could be separated from the auxiliary, without any loss of optical purity of both components.

Optically pure 2-(quinolin-8-yloxy)cyclohexan-1-ol as a practical agent for molecular recognition by NMR and fluorescence spectroscopy.

Optically pure 2-(quinolin-8-yloxy)cyclohexan-1-ol 1, obtained via simple chemical and bio-catalytic steps, was used as a chiral solvating agent for molecular recognition of the enantiomers of acids. The discrimination of isomers was detected by NMR or fluorescence spectroscopy. Isomers of α-substituted carboxylic acids, phosphoric acids, unprotected amino acids and dipeptides were efficiently detected, while the method can be used for quantitative determination for practical applications. Analysis of the crystal of (R,R)-1 (R)-mandelic acid established a three point supramolecular interaction.

Enantiomerically Pure 5,13-Dicyano-9-oxa[7]helicene: Synthesis and Study.

Optically pure dicyano oxa[7]helicenes and helicene-like molecules have been prepared and investigated for their optical behavior. The isomers of the intermediate 4,4'-biphen-anthrene-3,3'-diol were resolved by physically separating their 1-menthyl carbonate derivatives. In this work a mild method was developed to cleave ArOMe in presence of a cyano group. The optical rotation of atropisomeric diol, helicenes-like compounds and the oxa[7]helicenes was observed to be in increasing order, while the molecules also showed good response to circularly polarized luminescence.

Application of Roof-Shape Amines as Chiral Solvating Agents for Discrimination of Optically Active Acids by NMR Spectroscopy: Study of Match-Mismatch Effect and Crystal Structure of the Diastereomeric Salts.

Optically active roof-shape amines were prepared and scanned as chiral solvating agents to study molecular recognition of acids by NMR analysis. Three types of amines were studied to establish a match-mismatch effect for structurally diverse acid analytes. Single-crystal X-ray diffraction analysis was performed on the diastereomeric salts of roof-shape amines and both isomers of mandelic acid to establish molecular conformation and correlate the absolute configuration with the observed NMR shift. The present system also recognizes the two isomers of weakly acidic BINOL and its derivatives.

Synthesis and Photophysical Properties of Aza[n]helicenes.

Synthesis and study of aza[7]helicene and aza[9]helicene is presented in this paper. Photo-dehydrocyclization of the 3,6-bis-styryl derivative of carbazole leading to sterically less demanding aza[7]helicene resulted in smooth reaction, and only the desired angular-angular product was detected. However, in the case of aza[9]helicene, along with the expected angular-angular cyclization, three other products involving linear mode of cyclization were also isolated and characterized. In this case, the helical compound aza[9]helicene was predominantly formed at lower concentration while the other isomers were obtained at higher concentration. All of the compounds formed by angular-angular, angular-linear, and linear-linear modes of cyclization were fully characterized, and their photophysical properties were investigated.

Synthesis and characterization of chiral aza-macrocycles and study of their enantiomer recognition ability for organo-phosphoric acid and phosphonic acid derivatives by ³¹P NMR and fluorescence spectroscopy.

Two diastereomers of optically active N,O-containing new macrocycles with dual chirality of the ring and pendent group were synthesized and characterized. The difference in the accessibility of the cavity was explored to discriminate the enantiomers of the derivatives of organo-phosphoric and phosphonic acids by (31)P NMR and fluorescence spectroscopy.

Synthesis and Study of 7,12,17-Trioxa[11]helicene.

Synthesis of the title compound 7,12,17-trioxa[11]helicene, a large oxygen-containing helicene, has been reported. The 11-membered heterohelicene was synthesized by a combination of two simple reactions involving oxidative coupling and dehydrative cyclization. The final helicene was characterized by single-crystal X-ray diffraction, fluorescence spectroscopy, and differential scanning calorimetric analysis.

Steric considerations on improving the diastereomeric ratio of (+)- and (-)-neomenthyl phenyl sulfoxides using bulky-headed oxidant hexadecyltrimethylammonium periodate and assignment of their configuration.

The bulky-headed oxidant hexadecyltrimethylammonium periodate affords the diastereomeric pairs, (Ss)-(+)/(Rs)-(+) and (Ss)-(-)/(Rs)-(-)-neomenthyl phenyl sulfoxides in stereochemically pure states with improved diastereomeric excess (48% diastereomeric excess [de]) as compared to its nonbulky counterpart, sodium metaperiodate (28% de) from respective (+)/(-)-neomenthyl phenyl sulfides. Steric effects involving the head group volume of hexadecyltrimethylammonium periodate is found to play a role in improving the diastereomeric ratio of the products. The two diastereomers can be readily separated by column chromatography. Absolute configuration at the sulfur center in (+)-neomenthyl phenyl sulfoxide was determined by single-crystal X-ray crystallography and found to be Ss. Relative configurations of other sulfoxides were assigned based on the configuration of (+)-neomenthyl phenyl sulfoxide.

Synthesis of enantiomerically pure helicene like bis-oxazines from atropisomeric 7,7'-dihydroxy BINOL: Preliminary measurements of the circularly polarized luminescence.

Racemic sample of 2,2',7,7'-tetrahydroxy-1,1'-binaphthyl was resolved with (S)-proline and the separated enantiomers were independently converted to atropisomeric bis-oxazines by aromatic Mannich reaction. These chirally pure oxazines were then converted to the helicene like cyclic ethers. The Circularly Polarized Luminescence (CPL) profile was consistent with the isolation of the targeted helical-like molecules in optically pure form, prepared from the achiral primary amines. The compounds of interest displayed active and opposite CPL activities for each sets of the helicene like isomers (P)-/(M)-3 and (P)-/(M)-5.

Synthesis of chiral bis-oxazines: a preliminary assessment of helical conformational framework.

A series of novel naphthalene attached bis-oxazines were synthesized and characterized. The bis-oxazines were studied by VT-NMR analysis to assess the possibility of conformational twist. The bis-oxazine prepared from (l)-methylvalinate show a helical conformational twist in the single crystal X-ray analysis. Three isomers of bis-oxazines were prepared from chiral α-methylbenzyl amines, the meso isomer showed small optical rotation probably indicating the helical conformational twist in the molecule.

Synthesis of chiral helical 1,3-oxazines.

A series of novel 1,3-oxazines were prepared to construct a helical framework. The 1,3-oxazine attached to the phenanthrene unit showed a small bite angle θ (∼12°), while the units attached to [4]helicene showed a larger θ (∼35°) and exhibited helical isomers at ambient conditions. The diastereomers of the third type of helicene-like bis-oxazine attached to binaphthyl were easily separable and showed good thermal stability. All four diastereomers of bis-helicene were synthesized, and their absolute configuration was established.

Investigation of the Effects of the Structure and Chelate Size of Bis-oxazoline Ligands in the Asymmetric Copper-Catalyzed Cyclopropanation of Olefins: Design of a New Class of Ligands.

A set of novel, C(2)-symmetric bis-oxazoline ligands has been synthesized by mounting two oxazoline rings onto an optically active 1,3-dioxolane backbone. This design allows for the control of both orientation as well as the proximity of the oxazolinyl R-groups around the reactive site. As a result of the twist imparted by the 1,3-dioxolane ring, the stereogenic oxazolinyl substituents can be brought either toward or away from the complexed metal in a controllable fashion. Starting from L-amino alcohols and either L- or D-tartaric acid, two sets of ligands (6b-e and 7a,b) were synthesized and evaluated in the copper-catalyzed cyclopropanation of olefins. The comparison of benzyl and isopropyl derivatives of these ligands with previously reported five- and six-membered bis-oxazolines clearly indicates the beneficiary effect of the larger chelate size and the chiral tether of the tartrate-derived ligand. The effect of the different oxazolinyl groups along with the different substituents on the dioxolane tethers was also investigated. The influence of the alkyl group of the diazoacetate was studied, and the diazoacetate derived from (-)-8-phenylmenthol was found to be superior to (-)-menthyl diazoacetate. The cyclopropanation of vinyl acetate, a relatively unexplored substrate for this reaction, furnished cyclopropanol derivatives in good optical purity.