The Preparation of Enantiopure [6]‐ and [7]Helicenes from Binaphthanol

A general and efficient synthetic methodology for the preparation of enantio‐ and diastereopure [6]‐, and [7]helicenes is developed. Commercially available chiral binaphthanols are utilized to generate the arylene‐vinylene precursors, which undergo helical folding via photocyclization to give enantio‐ and diastereopure [6]‐, and [7]helicenes. These optically pure helicenes could be easily obtained via silica gel column chromatography without the use of expensive HPLC or chiral resolution reagents. The configurations and structures of these helicenes are confirmed by CD spectra and X‐ray crystallographic analysis. This work provides a new method for preparation of enantiopure helicenes.     

Closed Pentaaza[9]helicene and Hexathia[9]/[5]helicene: Oxidative Fusion Reactions of ortho‐Phenylene‐Bridged Cyclic Hexapyrroles and Hexathiophenes

Oxidative fusion reactions of ortho ‐phenylene‐bridged cyclic hexapyrroles and hexathiophenes furnished novel closed helicenes in a selective manner. X‐Ray diffraction analysis unambiguously revealed the structures to be a closed pentaaza[9]helicene, the longest azahelicene reported so far, and an unexpected double‐helical structure of hexathia[9]/[5]helicene, whose formation was assumed to result from multiple oxidative fusion along with a 1,2‐aryl shift. The pentaaza[9]helicene exhibited well‐defined emission with high fluorescence quantum yield (Φ _F=0.31) among the known [9]helicenes. Chiral resolution of the racemic pentaaza[9]helicene and hexathia[9]/[5]helicene were achieved by chiral‐phase HPLC and the enantiomers were characterized by circular dichroism spectra and DFT calculations.     

Symmetric,Unsymmetrical, and Asymmetric [7]‐, [10]‐, and [13]Helicenes

Fully aromatic helicenes with more than one pitch‐length are illustrious synthetic targets with potential applications in advanced optical devices and nano‐electronics. The task of extending the length of fully conjugated helicenes past one pitch length is challenging. Now, the synthesis of a series of azaoxa[7]‐, [10]‐, and [13]helicenes is described. The synthesis is based on iterative oxidative furan formation between 3,6‐dihydroxycarbazoles and/or 2‐naphthols. The flexibility of the presented method allows the convenient and scalable synthesis of symmetric, unsymmetrical, and asymmetric homo‐chiral structures. The [13]helicenes can be synthetically functionalized both at the termini and the periphery. The full range of helicenes were characterized using NMR and optical spectroscopy (UV/Vis, fluorescence, and CD) along with single‐crystal X‐ray crystallography. The enantiomers of the [13]helicenes are the longest optically pure helicenes isolated to date.     

Symmetric,Unsymmetrical, and Asymmetric [7]‐, [10]‐, and [13]Helicenes

Fully aromatic helicenes with more than one pitch‐length are illustrious synthetic targets with potential applications in advanced optical devices and nano‐electronics. The task of extending the length of fully conjugated helicenes past one pitch length is challenging. Now, the synthesis of a series of azaoxa[7]‐, [10]‐, and [13]helicenes is described. The synthesis is based on iterative oxidative furan formation between 3,6‐dihydroxycarbazoles and/or 2‐naphthols. The flexibility of the presented method allows the convenient and scalable synthesis of symmetric, unsymmetrical, and asymmetric homo‐chiral structures. The [13]helicenes can be synthetically functionalized both at the termini and the periphery. The full range of helicenes were characterized using NMR and optical spectroscopy (UV/Vis, fluorescence, and CD) along with single‐crystal X‐ray crystallography. The enantiomers of the [13]helicenes are the longest optically pure helicenes isolated to date.     

Diastereoselective Strategies towards Thia[n]helicenes

In the present study, we have investigated different strategies for diastereoselective synthesis of thia[n]helicenes. We describe the introduction of different chiral auxiliaries at various positions and investigated their effect in the photocyclization reaction. Different chiral groups were placed at the sterically hindered position of the helical core and their interactions with various solvents and metals like copper were investigated. The use of Cu^I salts has led to high diastereoselectivity in the photocyclization process and we were successful in obtaining the thia[5]helicene in enantiomerically pure form in good yield. The single diastereomer obtained was characterized by X‐ray crystallography. From the study of the barrier of racemization of these thia[5]helicenes, the stability was found to be comparable to unsubstituted tetrathia[7]helicenes and substituted diazadithia[7]helicenes. This approach provides an easy access to enantiopure helicenes.     

Catalytic Asymmetric Synthesis of 8‐Oxabicyclooctanes by Intermolecular [5+2] Pyrylium Cycloadditions

Highly enantioselective intermolecular [5+2] cycloadditions of pyrylium ion intermediates with electron‐rich alkenes are promoted by a dual catalyst system composed of an achiral thiourea and a chiral primary aminothiourea. The observed enantioselectivity is highly dependent on the substitution pattern of the 5π component, and the basis for this effect is analyzed using experimental and computational evidence. The resultant 8‐oxabicyclo[3.2.1]octane derivatives possess a scaffold common in natural products and medicinally active compounds and are also versatile chiral building blocks for further manipulations. Several stereoselective complexity‐generating transformations of the 8‐oxabicyclooctane products are presented.     

Transformation of Thia[7]helicene to Aza[7]helicenes and [7]Helicene-like Compounds via Aromatic Metamorphosis

[n]Helicenes with helically twisted structures have attracted increasing interest owing to their unique properties. Therefore, it has been an important issue to develop facile synthetic methodologies which allow access to a variety of [n]helicenes. Here we report the synthesis of [7]helicenes and [7]helicene-like compounds from the thia[7]helicene as a common starting material. Desulfurative dilithiation of the thia[7]helicene and the subsequent reaction with silicon and phosphorus electrophiles afforded the silole- and phosphole-fused [7]helicene-like compounds, respectively. The cyclopentadiene-fused [7]helicene-like compound and the pyrrole-fused aza[7]helicenes were also successfully synthesized via twofold S_NAr reactions of the thia[7]helicene S,S-dioxide with the carbon and nitrogen nucleophiles, respectively. The thia[7]helicene S,S-dioxide showed a slightly red-shifted absorption spectrum than the parent thia[7]helicene, which was well demonstrated by the theoretical calculations. The substituents on the silicon atom of silole-fused [7]helicene-like compounds have little impact on the longest absorption maximum. Such little effect of the substituents on absorption properties was also observed for cyclopentadiene-fused [7]helicene-like compounds and aza[7]helicenes and was well demonstrated by the theoretical calculations. The thia[7]helicene S,S-dioxide and the silole-fused [7]helicene-like compound exhibited bright blue emission, and the cyclopentadiene-fused [7]helicene-like compound and the aza[7]helicenes showed strong violet emission. Each single enantiomer of the aza[7]helicenes showed circularly-polarized luminescence with the dissymmetry factors of 4.2~4.4 × 10⁻³.     

Enantioselective Synthesis of 1-Aryl Benzo[5]helicenes Using BINOL-Derived Cationic Phosphonites as Ancillary Ligands

The synthesis of unprecedented BINOL-derived cationic phosphonites is described. Through the use of these phosphanes as ancillary ligands in Au^I catalysis, a highly regio- and enantioselective assembly of appropriately designed alkynes into 1-(aryl)benzo[5]carbohelicenes is achieved. The modular synthesis of these ligands and the enhanced reactivity that they impart to Au^I-centers after coordination have been found to be the key features that allow an optimization of the reaction conditions until the desired benzo[5]helicenes are obtained with high yield and enantioselectivity.     

Preparation and structural properties of 7,8-dioxa[6]helicenes and 7a,14c-dihydro-7,8-dioxa[6]helicenes.

The potentially chiral 7,8-dioxa[6]helicenes 1-1c have been prepared by oxidation of their precursors the 7a,14c-dihydro-7,8-dioxa[6]helicenes 3. The crystal structure determination of 3b cis-7a,14c-dihydro-3,12-dibromo-7,8-dioxa[6]helicene unambiguously confirms the cis configuration of the 7a,-14c hydrogens in compounds 3 as previously implied from NMR measurements and also shows that 3b crystallizes in a chiral conformation in the solid state. Selective deuteration of the sterically crowded 1,14 positions of 7,8-dioxa[6]helicene 1 influenced the crystal structure. The deuterium labeled compound D2-1 exhibits a disordered structure, whereas 1 had been found to crystallize in a complex structure which can be described as an analogous partly ordered modulated superstructure. When dehydrogenation of compound 3 to obtain compound 1 was attempted, harsh synthetic conditions gave the unexpected halogenated compounds 5-chloro-7,8-dioxa[6]helicene 1c and cis-7a,14c-dibromo-7,8-dioxa[6]helicene 3c. Compounds 1d and 3b were identified by solving their crystal structure.     

Diazadithia[7]helicenes: Synthetic Exploration,Solid‐State Structure,and Properties

Diazadithia[7]helicenes were synthesized from the readily available building block ethyl 7‐chloro‐8‐formylthieno[3,2‐f]quinoline‐2‐carboxylate by a Wittig reaction–photocyclization strategy. The helicene core was functionalized by nucleophilic aromatic substitution with a variety of nucleophiles (e.g., O‐, N‐, and C‐centered) and palladium‐catalyzed reactions such as Suzuki coupling and Buchwald–Hartwig amination. Racemization studies confirmed that the enantiopure forms of these [7]helicenes are conformationally stable compared to their lower analogues. The solid‐state structures of the novel diazadithia[7]helicenes were determined by single‐crystal X‐ray diffraction. The crystal structures of these azathia[7]helicenes show columnar stacking in antiparallel fashion. The HOMO–LUMO gaps of the new compounds were determined on the basis of electrochemical and optical measurements.     

Copper‐Catalyzed Enantio‐, Diastereo‐, and Regioselective [2,3]‐Rearrangements of Iodonium Ylides

The first highly enantioselective, diastereoselective, and regioselective [2,3]‐rearrangement of iodonium ylides has been developed as a general solution to catalytic onium ylide rearrangements. In the presence of a chiral copper catalyst, substituted allylic iodides couple with α‐diazoesters to generate metal‐coordinated iodonium ylides, which undergo [2,3]‐rearrangements with high selectivities (up to >95:5 r.r., up to >95:5 d.r., and up to 97 % ee ). The enantioenriched iodoester products can be converted stereospecifically into a variety of onium ylide rearrangement products, as well as compounds that are not accessible by classical onium ylide rearrangements.     

Nanographene Imides Featuring Dual‐Core Sixfold [5]Helicenes

A novel kind of nanographene imide, namely pentaperylene decaimides (PPD) featuring dual‐core sixfold [5]helicenes and ten imide groups, was efficiently obtained. Among the possible 28 stereoisomers, which include 14 pairs of enantiomers, only one pair of enantiomers was obtained selectively which could be separated by chiral HPLC. Single‐crystal X‐ray diffraction analyses revealed that it exhibits a D₂‐symmetric “four‐bladed propeller” conformation composed of conjoined double “three‐bladed propeller”, which is very stable and could not convert into other conformations even when heated up to 200 °C. Meanwhile, enantiomerically pure PPD also exhibits an excellent resistance to thermally induced racemization, which makes it a promising candidate for various applications in chiral material science.     

Stereoselective Chiral Molecular Carbon Imides Featuring 12-Fold [5]helicenes Around Four Cores**

Despite the great progress in research on molecular carbons containing multiple helicenes around one core, realizing the stereoselectivity of carbons containing multiple helicenes around more cores is still a great challenge. Herein, molecular carbon C₂₀₄ featuring 12-fold [5]helicenes around four cores was successfully constructed by using nine perylene diimide (PDI) units, and exhibits good solubility and stability. Despite 256 possible stereoisomers caused by the 12-fold [5]helicenes, we only obtained one pair of enantiomers with D₃ symmetry. There are four possible pairs of enantiomers with D₃ symmetry, namely 7A, 7B, 7C and 7D. Theoretical and experimental results verify that the obtained structure belongs to 7C, which has the lowest energy. The enantiomers can also be separated by chiral HPLC. These results suggest that choosing PDIs as building blocks can not only improve the solubility and stability but also realize the stereoselectivity and chirality of molecular carbons.     

Compressing a Non-Planar Aromatic Heterocyclic [7]Helicene to a Planar Hetero[8]Circulene

This work describes a synthetic approach where a non-planar aromatic heterocyclic [7]helicene is compressed to yield a hetero[8]circulene containing an inner antiaromatic cyclooctatetraene (COT) core. This [8]circulene consists of four benzene rings and four heterocyclic rings, and it is the first heterocyclic [8]circulene containing three different heteroatoms. The synthetic pathway proceeds via a the flattened dehydro-hetero[7]helicene, which is partially a helicene and partially a circulene: it is non-planar and helically chiral as helicenes, and contains a COT motif like [8]circulenes. The antiaromaticity of the COT core is confirmed by nucleus independent chemical shift (NICS) calculations. The planarization from a helically π-conjugated [7]helicene to a fully planar heterocyclic [8]circulene significantly alters the spectroscopic properties of the molecules. Post-functionalization of the [7]helicenes and the [8]circulenes by oxygenation of the thiophene rings to the corresponding thiophene-sulfones allows an almost complete fluorescence emission coverage of the visible region of the optical spectrum (400–700 nm).     

Theoretical and experimental studies on circular dichroism of carbo[n]helicenes

The chiroptical properties of a series of carbo[n]helicenes (n = 4-10) were investigated by the state-of-the-art approximate coupled cluster and density functional theory calculations. The theoretical calculation at the RI-CC2/TZVPP//DFT-D2-B97-D/TZVP level nicely reproduced the experimental CD spectra in both excitation energy and rotational strength without any shift or scaling. These calculations afforded the electric and the magnetic transition dipole moment vectors in [n]helicenes, allowing us to discuss the observed rotational strengths as a function of the number of benzene rings. Although the observed CD intensity was not immediately correlated to any of the calculated parameters, the anisotropy (g) factor of the (1)B(b) band and the specific rotation were found inversely proportional to n and nicely correlated with the helical pitch, but discontinuous at n = 6, where the aromatic rings start to overlap. In contrast, the g factor at the (1)B(a) band was rather insensitive to n. It was also revealed that the excitation energies of the (1)B(b) and (1)B(a) bands are inversely proportional to n over the entire range of n examined. The theoretical predictions also enabled us to rectify the erroneous experimental CD spectra of [5]- and [6]helicenes reported earlier, by using the enantiopure samples resolved by chiral HPLC.     

Synthesis of [5]-, [6]-, and [7]helicene via Ni(0)- or Co(I)-catalyzed isomerization of aromatic cis,cis-dienetriynes

An original approach to helicene frameworks exploiting atom economic isomerization of appropriate energy-rich aromatic cis,cis-dienetriynes has been developed. The new paradigm provides nonphotochemical syntheses of helicenes based on the easy, convergent, and modular assembly of key cis,cis-dienetriynes and their nickel(0)-catalyzed [2+2+2] cycloisomerization. The potential of the methodology is underlined by the syntheses of the parent [5]helicene (2), 7,8-dibutyl[5]helicene (23), [6]helicene (24), and [7]helicene (25). The approach can be adapted to prepare functionalized helicenes as exemplified by the eight-step synthesis of 7,8-dibutyl-2,3-dimethoxy[6]helicene (34). Density functional theory (DFT) calculations showed that bis[2-((1Z)-1-buten-3-ynyl)phenyl]acetylene (1) and isomeric [5]helicene (2) differ enormously in the Gibbs energy content (DeltaG = -136.6 kcal x mol(-1)) to favor highly the devised intramolecular simultaneous construction of three aromatic rings.     

Enantioselective Synthesis of 1,12‐Disubstituted [4]Helicenes

A highly enantioselective synthesis of 1,12‐disubstituted [4]carbohelicenes is reported. The key step for the developed synthetic route is a Au‐catalyzed intramolecular alkyne hydroarylation, which is achieved with good to excellent regio‐ and enantioselectivity by employing TADDOL‐derived (TADDOL=α,α,α,α‐tetraaryl‐1,3‐dioxolane‐4,5‐dimethanol) α‐cationic phosphonites as ancillary ligands. Moreover, an appropriate design of the substrate makes the assembly of [4]helicenes of different substitution patterns possible, thus demonstrating the synthetic utility of the method. The absolute stereochemistry of the newly prepared structures was determined by X‐ray crystallography and characterization of their photophysical properties is also reported.     

Carbo[n]helicenes Restricted to Enantiomerize: An Insight into the Design Process of Configurationally Stable Functional Chiral PAHs

The most important stereodynamic feature of carbo[n]helicenes is the interconversion of their enantiomers. The Gibbs activation energy (ΔG^≠(T)) of this process, which determines the rate of enantiomerization, dictates the configurational stability of [n]helicenes. High values of ΔG^≠(T) are required for applications of functional chiral molecules incorporating [n]helicenes or helicene substructures. This minireview provides an overview of the mechanism, recent developments, and factors affecting the enantiomerization of [n]helicenes, which will accelerate the design process of configurationally stable functional chiral molecules based on helicene substructures. Additionally, this minireview addresses the misconception and irregularities in the recent literature on how the terms “racemization” and “enantiomerization” are used as well as how the activation parameters are calculated for [n]helicenes and related compounds.     

On the Physicochemical Properties of Pyridohelicenes

A comprehensive study on the physicochemical properties of a series of mono‐ and diaza[5]helicenes as well as mono‐ and diaza[6]helicenes is reported. Through the use of both computational and experimental methods, these helically chiral pyridohelicenes with the nitrogen atom(s) in various positions are characterised according to their inversion barriers, protonation constants and redox potentials. By using DFT calculations, kinetic measurements, UV/Vis titrations, cyclic voltammetry and EPR spectroscopy, a self‐contained picture of their behaviour under conventional treatment by heat, acids and oxidising/reducing agents is provided.     

Local aromaticity of [n]acenes, [n]phenacenes, and [n]helicenes (n = 1-9)

The local aromaticity of the six-membered rings in three series of benzenoid compounds, namely, the [n]acenes, [n]phenacenes, and [n]helicenes for n = 1-9, has been assessed by means of three probes of local aromaticity based on structural, magnetic, and electron delocalization properties. For [n]acenes our analysis shows that the more reactive inner rings are more aromatic than the outer rings. For [n]phenacenes, all indicators of aromaticity show that the external rings are the most aromatic. From the external to the central ring, the local aromaticity varies in a damped alternate way. The trends for the [n]helicene series are the same as those found for [n]phenacenes. Despite the departure from planarity in [n]helicenes, only a very slight loss of aromaticity is detected in [n]helicenes as compared to the corresponding [n]phenacenes. Finally, because of magnetic couplings between superimposed six-membered rings in the higher members of the [n]helicenes series, we have demonstrated that the NICS indicator of aromaticity artificially increases the local aromaticity of their most external rings.