Room‐Temperature Helix‐to‐Disc Conversion of Thia[6]helicene S,S‐Dioxides to Coronene via In Situ Phenoxide Anion Generation

ABSTRACT

Intramolecular annulation between the helical termini of helicenes provides a direct route to circulene‐type architectures. In thia[6]helicene, oxidation at the thiophene terminus to the S,S‐dioxide facilitates the thermal conversion to coronene, but established protocols typically require elevated temperatures. Herein, we demonstrate that forming a phenoxide anion at the benzene terminus of thia[6]helicene S,S‐dioxides enables this transformation at room temperature, affording coronene in near‐quantitative yield. Phenoxide arises either by deacetylation of the acetate precursor or by deprotonation of the corresponding phenol. Owing to the solubility contrast between the helical precursor and planar coronene, the product precipitates from solution, allowing the conversion to be monitored visually, and can be isolated by simple filtration. This helix‐to‐disc conversion begins with a stepwise intramolecular Diels–Alder reaction, and computational analysis elucidates the complete pathway to coronene. The present strategy delivers a practical room‐temperature route to planar aromatic frameworks via an anion‐triggered Diels–Alder reaction, without oxidative Scholl‐type conditions, and broadens opportunities for the late‐stage planarization of helicenes and related π‐systems.

In situ phenoxide formation at the benzene terminus triggers room‐temperature conversion of thia[6]helicene S,S‐dioxides to coronene. The solubility contrast drives product precipitation, enabling isolation by simple filtration. This pericyclic annulation between the helical termini provides direct access to coronene‐type planar architectures.

1. Introduction

The skeletal transformation of nonplanar π‐conjugated molecules into planar polycyclic aromatic frameworks represents a powerful synthetic strategy for reconfiguring molecular topology and accessing π‐extended architectures [1, 2, 3, 4, 5]. Within this paradigm, transformations into circulene‐type systems have proven particularly effective for constructing circumarenes formed by annulation around a central aromatic core [6, 7, 8, 9, 10]. Beyond structural reconfiguration, soluble precursors are often converted into less‐soluble products upon planarization, unless solubilizing substituents are incorporated into their final frameworks. Although this decrease in solubility may appear disadvantageous at first glance, it becomes a practical advantage when the conversion is clean and efficient. In such cases, precipitation enables the straightforward isolation and purification of otherwise intractable planar polycyclic aromatics.

The concept of connecting the helical termini of helicenes to effect planarization dates back to the 1970s, when Wynberg et al. explored the Scholl‐type reactions of sulfur‐containing helicenes (thiahelicenes) (Scheme 1a) [11, 12, 13]. Some thia[5] and thia[6]helicenes, with outward‐oriented sulfur atoms, underwent intramolecular ring closure, whereas the parent carbo[6]helicene did not. The resulting dehydrohelicenes featured newly formed bay regions that underwent Diels–Alder reactions with maleic anhydride, introducing two additional carbon atoms into the frameworks. Subsequent pyrolysis with soda lime induced decarboxylation of the Diels–Alder adducts, yielding heterocirculenes. This stepwise strategy—intramolecular Scholl‐type cyclization followed by bay‐region annulation—laid the foundation for planarizing helicenes and constructing π‐extended architectures.

SCHEME 1.

Previously developed strategies for connecting the helical termini of helicenes. Synthesis of a) hetero[7]circulene and b) hetero[8]circulene via intramolecular cyclization followed by bay‐region annulation.

More recently, alternative strategies have emerged that enable the direct construction of heterocirculenes from helicene precursors without isolating dehydrohelicene intermediates. For example, Pittelkow et al. reported a sequential annulation strategy in which 2,7‐dimethoxy‐substituted hetero[7]helicenes underwent oxidative cyclodehydrogenation under Scholl‐type conditions to afford fully planarized hetero[8]circulenes (Scheme 1b) [14]. This transformation begins with intramolecular C–C bond formation to close the inner ring, followed by cyclodehydration of the two terminal OH groups to furnish the outer furan ring. Building on this strategy, Ema et al. applied a similar approach to access saddle‐shaped hetero[8]circulenes, [15, 16] highlighting its applicability to a broader range of nonplanar heterocirculenes.

In contrast to the widely employed Scholl‐type approach, we demonstrated that thia[6]helicene with an inward‐oriented sulfur atom at the terminal thiophene ring transforms into [6]circulene (i.e., coronene) under UV light irradiation [17]. This “helix‐to‐disc” conversion becomes thermally accessible upon S‐oxidation of the thiophene ring to the corresponding S,S‐dioxide 1a (Scheme 2; R = H). The skeletal transformation of 1a starts with intramolecular Diels–Alder cyclization (1a→2a), followed by cheletropic extrusion of sulfur dioxide (2a→3a) and aromatization of the 9,10‐dihydronaphthalene moiety (3a→coronene). Our pericyclic strategy links the helical termini to form coronene‐type fused systems, bypassing bay‐region annulation and providing a direct pathway to circulene‐type planarization. Note that the transformation is driven by external stimuli and requires no additional oxidants, underscoring its operational simplicity.

SCHEME 2.

Pericyclic annulation at the helical termini of thia[6]helicene S,S‐dioxides 1 to give coronene. Helical structures are shown as the M enantiomer for clarity, but all samples were used as racemic mixtures.

However, the transformation of 1a still requires relatively harsh conditions, typically heating to 160°C for efficient coronene formation. At lower temperatures, such as 100°C, the reaction becomes sluggish and leads to the deposition of uncharacterized insoluble material, which diminishes efficiency. Seeking a route that would permit lower temperatures, we examined substituent effects and reaction conditions. Herein, we demonstrate that forming aryloxide (ArO⁻) 1b, with O⁻ directly bound at the benzene terminus, enables clean and near‐quantitative helix‐to‐disc conversion to coronene at room temperature (Scheme 2). Notably, 1b undergoes smooth conversion, whereas the corresponding conjugate acid (ArOH) 1c remains unreactive at room temperature. Density functional theory (DFT) calculations provide a mechanistic rationale for this aryloxide‐enabled conversion to coronene, consistent with the observed ambient reactivity.

2. Results and Discussion

2.1. Synthesis of Functionalized Thia[6]helicene S,S‐Dioxides

In our previous reports on the synthesis of 1a, the helical framework was assembled starting from the terminal benzene ring, with the thiophene ring at the opposite terminus being introduced at the final stage [17, 18]. Although this approach was effective for preparing the parent framework, it was unsuitable for the present study, which required functionalization at the terminal benzene ring. In particular, when the optimal substituent has not been predetermined at the outset, this synthetic order offers limited versatility in the late‐stage introduction of functional groups.

To address this limitation, we redesigned the synthetic route to enable late‐stage functionalization, as shown in Scheme 3. A Mizoroki–Heck reaction between commercially available 6‐bromobenzothiophene (4) and 4‐methylstyrene afforded compound 5 in 86% yield. Subsequent oxidative photocyclization of 5 afforded thia[4]helicene 6 in 85% yield. Benzylic bromination of 6 with N‐bromosuccinimide (NBS), followed by treatment with PPh₃, provided phosphonium salt 7 (61%, two steps). This salt served as a versatile substrate in the subsequent Wittig reaction for preparing functionalized thia[6]helicenes. In this study, the Wittig reaction of 7 with 4‐acetoxybenzaldehyde furnished stilbene 8 (94%), bearing an acetyl‐protected phenol functionality amenable to later deprotection. Subsequent oxidative photocyclization of 8 extended the helical framework to give thia[6]helicene 9 in 82% yield. Finally, the terminal thiophene moiety was oxidized with m‐chloroperbenzoic acid (m‐CPBA), affording acetoxy‐functionalized thia[6]helicene S,S‐dioxide 1d in 90% yield.

SCHEME 3.

Synthesis of 1d. Conditions: (i) 4‐methylstylene, NaOAc, Herrmann's catalyst, N,N‐dimethylacetamide, 130°C, 48 h; (ii) UV light, I₂, propylene oxide, toluene, rt, 1.5 h; (iii) NBS, AIBN, CCl₄, reflux, 16 h; (iv) PPh₃, toluene, reflux, 5 h; (v) 4‐acetoxybenzaldehyde, NaH, THF, 0°C, 16 h; (vi) UV light, I₂, propylene oxide, cyclohexane/toluene, rt, 20 min; (vii) m‐CPBA, CH₂Cl₂, rt, 6 h. rt: room temperature.

2.2. Conversion to Coronene via In Situ Phenoxide Anion Generation

When a CH₂Cl₂/MeOH (1:1) solution of 1d (49 mM) was treated with NaOMe (3.0 equiv.) at room temperature for deacetylation, the yellow solution immediately turned reddish orange (Scheme 4a). Upon continued stirring at room temperature, the solution gradually decolorized to pale yellow, accompanied by the precipitation of a yellow solid. After 6 h, the precipitate was collected by filtration to afford spectroscopically pure coronene in 64% yield (Figure S1). The supernatant contained dissolved coronene, but 1d was not detected by ¹H NMR. Subsequent concentration and trituration with MeOH gave additional coronene (34%), bringing the total isolated yield to 98%.

SCHEME 4.

a) Photographs illustrating the color and phase changes during the helix‐to‐disc conversion of 1d in CH₂Cl₂/MeOH (1:1) at room temperature. The lower panel shows TFA quenching of the NaOMe‐treated solution, affording 1c. b) Treatment of 1d with NaOMe in CH₂Cl₂/MeOH (7:1) at room temperature, which suppresses coronene formation and gives the deacetylated oxa‐Michael adduct 1c’, as a mixture of diastereomers (dr = 64:36). rt: room temperature; dr: diastereomeric ratio.

To capture the deacetylated product 1c before conversion to coronene, we immediately quenched the reaction with trifluoroacetic acid (TFA) after 3 min of NaOMe treatment, keeping other conditions unchanged (Scheme 4a). The reddish‐orange solution turned deep yellow, but no precipitate formed at this stage. After solvent removal, the addition of MeOH induced precipitation, and the mixture was filtered. NMR analysis of the precipitate and the filtrate confirmed complete deacetylation of 1d to give 1c, with a trace amount of coronene (Figure S2). The filtrate was then worked up and purified by column chromatography on silica gel to give an additional 1c‐rich fraction. Overall, 1c and coronene were obtained in 78% and 3% yields, respectively. Isolated 1c shows poor solubility in chlorinated solvents (CH₂Cl₂ and CHCl₃) and aromatic solvents (toluene and mesitylene) but readily dissolves in polar aprotic solvents (acetone and dimethyl sulfoxide (DMSO)).

Because 1c was stable at room temperature and only converted to coronene upon heating in DMSO (160°C, 1.5 h, 54%), we reasoned that the phenolic OH alone did not provide sufficient electron donation to trigger the transformation at room temperature. Accordingly, we hypothesized that deprotonation to aryloxide 1b would enhance electron donation at the dienophilic benzene ring and promote the transformation. Consistent with this hypothesis, treatment of 1c with NaOMe turned the yellow solution reddish orange again. The reaction then smoothly proceeded to afford coronene, confirming that 1b is the reactive species responsible for the room‐temperature helix‐to‐disc conversion.

Moreover, the solvent composition proved crucial for directing the reaction pathway. The transformation of 1d proceeded cleanly in CH₂Cl₂/MeOH (1:1), but this solvent mixture serves not only to facilitate the precipitation of coronene but also to prevent the competing oxa‐Michael addition [19, 20, 21] of MeO⁻ to the electron‐deficient thiophene S,S‐dioxide unit [22, 23]. A higher MeOH content is expected to attenuate the effective nucleophilicity of MeO⁻ through protic solvation and hydrogen bonding, thereby disfavoring this oxa‐Michael pathway. At the same time, MeOH‐rich conditions promote deacetylation by facilitating the methanolysis of acetate 1d. When the reaction was carried out in CH₂Cl₂/MeOH (7:1), coronene formation was suppressed (44%), and the deacetylated oxa‐Michael adduct 1c’ was obtained in 36% yield, along with 1c in 5% yield (Scheme 4b). This methoxide addition at the β‐position of the thiophene S,S‐dioxide unit disrupts the conjugated diene motif required for the intramolecular Diels–Alder step, thereby suppressing the helix‐to‐disc conversion under CH₂Cl₂‐rich conditions.

2.3. DFT‐Supported Mechanism of Coronene Formation

Historically, intramolecular Diels–Alder reactions of helicenes and subsequent spontaneous transformations have not yielded planar frameworks as final products [24, 25, 26, 27, 28, 29, 30, 31]. Within [7]helicene frameworks, the terminal benzene ring couples with the second distal benzene ring, leaving the opposite terminal ring outside the fused core. Efficient conversion has required strong activation, such as the generation of a benzyne dienophile at the terminal ring, [25] Lewis‐acid mediation, [26, 27] high‐temperature annealing on Ag surfaces, [28] or photochemical excitation [29, 30, 31]. Against this background, it is remarkable that 1b can undergo a helix‐to‐disc conversion to coronene at room temperature, necessitating further investigation.

To address this, we conducted DFT calculations; specifically, geometry optimization and frequency calculations were performed at the M06‐2X/6‐31+G(d,p) level with the conductor‐like polarizable continuum model (CPCM) (for MeOH). Single‐point energies were refined at the M06‐2X/6‐311+G(2d,p) level with the solvation model based on density (SMD) (for MeOH). The free energies reported at 298 K combine the SMD/6‐311+G(2d,p) electronic energies with the CPCM/6‐31+G(d,p) thermal corrections (for details, see the Supporting Information).

As a preliminary validation, we first examined the intramolecular Diels–Alder reaction of 1c at 298 K (Figure 1). The calculations indicate a concerted asynchronous pathway with a single transition state (TS10) located at an activation free energy of 33.5 kcal mol⁻¹ (34.6 kcal mol⁻¹ in DMSO at 433 K reflects the experimental conditions), consistent with the lack of reactivity of 1c at room temperature (Figure 1b). The forming C─C bond on the inner helix (1.72 Å) is more advanced than that on the outer helix (2.88 Å). The computed reaction free energy for 1c→2c is 0.5 kcal mol⁻¹, indicating an essentially thermoneutral process. Frontier orbital analysis further supports an inverse electron‐demand character in which the highest occupied molecular orbital (HOMO) is localized on the electron‐rich terminal phenol ring (dienophile), whereas the lowest unoccupied molecular orbital (LUMO) is located on the electron‐deficient thiophene S,S‐dioxide ring (diene) (Figure 1a). Such intramolecular inverse electron‐demand Diels–Alder reactions involving thiophene S,S‐dioxides have recently attracted considerable attention as powerful tools for the rapid construction of complex molecular architectures [32, 33, 34, 35, 36]. Anticipating that deprotonation would raise the dienophilic HOMO and lower the activation free energy, we next analyzed the anionic species 1b. However, no concerted pathway was identified for 1b, suggesting that the reaction proceeded in a stepwise fashion.

FIGURE 1.

DFT analysis for the intramolecular Diels–Alder reaction of 1c to 2c. a) HOMO and LUMO isosurfaces of 1c at an isovalue of 0.07. b) Concerted asynchronous transition state TS10 with forming C─C bonds of 1.72 Å on the inner helix and 2.88 Å on the outer helix. The calculated energies (kcal mol⁻¹) relative to 1c are shown in parentheses. Energies were computed at the SMD(MeOH)‐M06‐2X/6‐311+G(2d,p) level on CPCM(MeOH)‐M06‐2X/6‐31+G(d,p) geometries at 298 K.

A stepwise pathway involving an initial Michael‐type addition followed by an intramolecular aldol‐type addition is characteristic of Diels–Alder reactions between highly polarized diene–dienophile pairs [37, 38, 39, 40, 41, 42, 43]. In line with this mechanistic paradigm, the reaction of 1b was found to proceed in a stepwise manner (Figure 2). The first transition state (TS11) corresponds to C–C bond formation within the inner helix, leading to intermediate A. This intermediate displays a newly formed C–C bond of 1.58 Å, while the remaining reactive carbons are separated by 3.26 Å, reflecting a partially completed cycloaddition. Intermediate A subsequently undergoes the second C–C bond formation via TS12 to furnish the Diels–Alder product 2b. The overall barrier for this Diels–Alder process is 18.5 kcal mol⁻¹, which is reduced by 15.0 kcal mol⁻¹ relative to the neutral species 1c, sufficient to render the reaction feasible at room temperature.

FIGURE 2.

Calculated relative free‐energy profile for the transformation of 1b into coronene. Relative Gibbs free energies are shown in kcal mol⁻¹. Geometric structures of key transition states (TS11–TS15) and intermediates (A, 2b, 3b, B) are shown with selected interatomic distances (Å). Energies were computed at the SMD(MeOH)‐M06‐2X/6‐311+G(2d,p) level on CPCM(MeOH)‐M06‐2X/6‐31+G(d,p) geometries at 298 K.

Although the Diels–Alder reaction of 1b to 2b is endergonic and thermodynamically uphill by 7.9 kcal mol⁻¹, the subsequent cheletropic extrusion of SO₂ (2b→3b) provides a strong thermodynamic driving force [32, 33, 34, 35, 36]. This step is exergonic (−23.5 kcal mol⁻¹) and proceeds with an almost negligible barrier (1.4 kcal mol⁻¹) via TS13, affording the partially saturated coronene oxide anion 3b. The substantial decrease in free energy associated with SO₂ release compensates for the unfavorable thermodynamics of the preceding Diels–Alder step, thereby driving the overall transformation toward the products.

Assuming an anionic pathway up to the elimination step that furnishes coronene, the late‐stage sequence begins with intramolecular proton abstraction; the bridgehead C─O⁻ unit of 3b deprotonates the adjacent bridgehead C─H. Computations show a modest barrier of 14.6 kcal mol⁻¹ for this proton transfer via TS14, forming carbanion B, which is stabilized by extensive conjugation. As illustrated in Figure 2, the optimized geometries show progressive planarization around the reacting bridgehead, from puckered 3b through TS14 to the nearly coplanar B. This conjugate base lies 24.7 kcal mol⁻¹ below 3b in free energy, and this stabilization promotes E1cB‐type elimination. The subsequent elimination step proceeds via TS15, and the loss of HO⁻ furnishes coronene. This elimination is strongly exergonic (−36.5 kcal mol⁻¹) and effectively barrierless, with the recovery of aromatic stabilization providing an additional driving force for the overall transformation.

3. Conclusion

We demonstrated that thia[6]helicene S,S‐dioxides underwent helix‐to‐disc conversion to coronene at room temperature, owing to the in situ generation of aryloxide 1b, which arises either by direct deprotonation of 1c or by deacetylation of 1d. Operationally, NaOMe in CH₂Cl₂/MeOH (1:1) gave a clean conversion, and the product precipitated, simplifying isolation. DFT calculations accounted for these observations. For 1c, a concerted intramolecular Diels–Alder pathway had a high barrier at 298 K, consistent with its lack of reactivity. For 1b, the Diels–Alder reaction proceeded stepwise and culminated in coronene formation. The helicene skeleton became progressively more planar along the pathway, consistent with the recovery of aromatic stabilization as an additional driving force. The present strategy, which exploits the intrinsic intramolecular Diels–Alder reactivity of helicenes, offers a simple route for constructing planar π‐extended frameworks at room temperature and broadens opportunities for the late‐stage planarization of helicenes and related π‐systems.

4. Experimental Section

4.1. Transformation of 1d into Coronene at Room Temperature

Thia[6]helicene S,S‐dioxide 1d (33.3 mg, 0.0785 mmol) was dissolved in CH₂Cl₂/MeOH (1.6 mL, 1:1 v/v). Then, a solution of NaOMe in MeOH (1.0 M, 0.235 mL, 0.235 mmol) was added dropwise, and the resulting solution (overall CH₂Cl₂/MeOH ≈ 1:1.3, v/v) was stirred at room temperature for 6 h. After thin‐layer chromatography confirmed completion of the reaction with a single new spot corresponding to coronene, the resulting precipitate was collected by filtration and washed with MeOH to give coronene (15.1 mg, 0.0503 mmol, 64%). The filtrate was concentrated by rotary evaporation, and MeOH (2 mL) was added. The suspension was heated at 45°C, and the resulting precipitate was collected by filtration and washed with cold MeOH to give coronene (5.1 mg, 0.0170 mmol, 22%). The mother liquor was again concentrated by rotary evaporation, MeOH (0.5 mL) was added, and the suspension was reheated at 45°C. The resulting precipitate was collected by filtration and washed with cold MeOH to give coronene (2.8 mg, 9.3×10⁻³ mmol, 12%). Thus, the total yield of coronene was 98% (23.0 mg, 0.0766 mmol). All isolated samples of coronene were confirmed to be analytically pure by ¹H NMR spectroscopy in CDCl₃, showing a single resonance at δ = 8.94 ppm (Figure S1).

4.2. Computational Methods

All DFT calculations were carried out with Spartan’24 (Wavefunction, Inc.) using the M06‐2X functional. Geometry optimizations and harmonic frequency calculations were performed at the M06‐2X/6‐31+G(d,p) level with the CPCM solvation model (MeOH), and single‐point electronic energies were refined at the M06‐2X/6‐311+G(2d,p) level with the SMD solvation model (MeOH) on the CPCM‐optimized geometries. All stationary points were characterized by frequency analyses (minima: no imaginary frequencies; transition states: one imaginary frequency). Gibbs free energies were obtained by combining single‐point electronic energies with thermal corrections from the frequency calculations.

Low‐frequency vibrational contributions were treated using a quasi‐harmonic approach to avoid the overestimation of entropic terms. A standard state correction from 1 atm to 1 M was applied using the conventional concentration correction (+1.89 kcal mol⁻¹ at 298.15 K). Explicit metal counterions (e.g., Na⁺) were not included to avoid model‐dependent contact or solvent‐separated ion pairs. Anionic species were treated as free anions within the continuum solvent model. Hydroxide was modeled using an effective free‐energy approach based on an HO⁻···MeOH cluster (see the Supporting Information for details). The experimental CH₂Cl₂/MeOH (1:1) medium was approximated as MeOH because the key elementary steps involve anionic species and specific hydrogen‐bonding/proton‐transfer stabilization dominated by the protic component, and the continuum treatment of mixed solvents is not always reliable.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

The authors have cited additional references within the Supporting Information [S1–S3].

Data Availability Statement

The data that supports the findings of this study are available in the supplementary material of this article