# Ethyl 4-Ene-4-ferrocenyl-5,5-bis-(4-hydroxyphenyl)-pentanoate

Jérémy Forté, Pascal Pigeon

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Jérémy Forté, Pascal Pigeon. Ethyl 4-Ene-4-ferrocenyl-5,5-bis-(4-hydroxyphenyl)-pentanoate. Molbank, 2025, Structure Determination, 2025 (1), pp.M1980. 10.3390/M1980.hal-04990488

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Short Note

# Ethyl 4-Ene-4-ferrocenyl-5,5-bis-(4-hydroxyphenyl)-pentanoate

Jérémy Forté<fnref n="1" /> ID and Pascal Pigeon <fnref n="1" />,<fnref n="2" />,* ID

**Abstract:** The ferrociphenol family is a group of molecules in which a ferrocenyl moiety is connected to at least one 4-hydroxyphenyl group through a C-C double bond. Among them, ferrocidiphenols in which the double bond is substituted by two gem 4-hydroxyphenyl groups have been largely studied, demonstrating interesting anticancer properties. The fourth available position of the double bond could be substituted by a simple ethyl group (1a) inherited from Tamoxifen, but also by ethyl or methyl acetate, propionate, butanoate, pentanoate (1b-g), hydroxyethyl or hydroxypropyl (1h-i). Ethyl 4-ene-4-ferrocenyl-5,5-bis-(4-hydroxyphenyl)-pentanoate 1e shows an IC₅₀ on the MDA-MB-231 breast cancer cell line very close to that of 1a. These compounds were synthesized in moderate to good yields by McMurry coupling reaction from the corresponding ketones. Ethyl 4-ene-4-ferrocenyl-5,5-bis-(4-hydroxyphenyl)-pentanoate (1e) was fully characterized by ¹H NMR (including COSY), ¹³C NMR (including DEPT135), low resolution mass spectrometry, HRMS, infrared spectroscopy, elemental analysis, and X-ray diffraction (XRD). The data of already published crystal structures of five structurally related ferrocidiphenols are also included for comparison purposes.

**Keywords:** ferrocene; ferrociphenol; ferrocidiphenol; anticancer molecules; organometallic compounds; McMurry reaction; X-ray diffraction; crystal structure

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Received: 25 February 2025

Revised: 7 March 2025

Accepted: 11 March 2025

Published: 13 March 2025

**Citation:** Forté, J.; Pigeon, P. Ethyl 4-Ene-4-ferrocenyl-5,5-bis-(4-hydroxyphenyl)-pentanoate. *Molbank* **2025**, *2025*, M1980. https://doi.org/10.3390/M1980

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## 1. Introduction

Research on the anticancer activities of ferrocene-containing molecules has been growing over the last 10 years [1–10]. Ferrociphenols are established molecules, showing high cytotoxic activity against various cancer cell lines. Part of their cytotoxic activity is associated with the integrated ferrocene-alkene-*p*-phenol motif (called the “Ferrociphenol motif”) and its ability to be oxidized into a quinone-methide metabolite [11] in cells. This reactive metabolite can covalently bind to biomolecules via Michael addition [12]. Interestingly, to act as a pharmacophore, the ferrocenyl and the phenol moieties should be *trans* to each other [13] (drawn in blue in Figure 1). Ferrocidiphenols, by the presence of the gem *p*-hydroxyphenyl groups in which all the molecules show the *trans* configuration, are efficient active compounds that are easily prepared. The central double bond of ferrocidiphenols is substituted by the ferrocenyl group and by two *p*-hydroxyphenyl moieties, leaving the fourth position available as a means of diversification. The historical and leading molecule in the non-cyclic ferrocidiphenol family is **1a**, which was first reported in 2005 [14]. The double bond of **1a** is substituted by an ethyl group inherited from its models, Tamoxifen and ferrocifen (the ferrocenic analog) [1]. During the twenty years following its discovery, we studied the diversification of these types of compounds and, particularly, the nature of the substituent occupying the fourth position on the alkene moiety. As we progressed in our

<footnote n="1">¹ Institut Parisien de Chimie Moléculaire (IPCM), CNRS, Sorbonne Université, 4 Place Jussieu, F-75005 Paris, France; jeremy.forte@sorbonne-universite.fr</footnote>

<footnote n="2">² Chimie ParisTech, PSL, 11 Rue Pierre et Marie Curie, F-75005 Paris, France</footnote>

<footnote>* Correspondence: pascal.pigeon@sorbonne-universite.fr or pascal.pigeon@chimieparistech.psl.eu</footnote>
knowledge of the mechanism of action of hydroxy-ferrocifen (the hydroxylated derivative of ferrocifen, leaving aside its SERM activity) and found it to be linked to the ferrociphenol motif, we considered that the ethyl group could and should be modified. We added more polar ester groups to the alkyl chain to study the effect of both the alkoxy group and the position of the carboxyl group (1b-g, Figure 1). Tested on the hormone-independent breast cancer cell line MDA-MB-231, the IC₅₀ were 0.6 µM for **1a** (no ester) [14], 0.39 µM for **1b** [15], 1.16 µM for **1c** [16], 0.44 µM for **1d** [17], 0.58 µM for **1e** (unpublished value and synthesis), 0.22 µM for **1f** [15], and 1.10 µM for **1g** [15]. Comparisons between **1b** and **1c** and between **1d** and **1e** indicated that a methyl ester was more favorable than an ethyl ester one. The relative position of the carboxyl group also seemed to have some influence on cytotoxicity (see **1b,d,f** and **g**), with the optimum chain length being observed for ester **1f**, which gave the lowest IC₅₀, i.e., around three times more active than **1a**. However, when ester **1d** was reduced to alcohol **1i**, the IC₅₀ decreased to 0.11 µM [17], the lowest among the non-cyclic ferrociphenols. Alcohol **1h**, possessing two methylenes [11], is less active compared to **1i** but still more active than the corresponding esters **1b-g**. Alcohols **1h** and **1i**, along with their ester's precursors **1d** and **1f**, were included in a patent. Most of the compounds reported in Figure 1 have been reported [11,15,17], except ester **1e**, which has taken a back seat, despite its quite good cytotoxic activity, because of the concomitant discovery of more active **1i**.

<figure><img src="image_3.png" /><figcaption>**Figure 1.** Examples of the diversity of the ferrocidiphenol family **1**, derived from Tamoxifen. The ferrociphenol motif is drawn in blue.</figcaption></figure>

Compound **1e** was synthesized by McMurry coupling reaction between a synthesized ferrocenyl ketone and a commercially available benzophenone. Ester **1e** was fully characterized by ¹H NMR, ¹³C NMR, COSY, infrared spectroscopy, low resolution mass spectrometry, HRMS, elemental analysis, and X-ray diffraction (XRD).

## 2. Results and Discussion

### 2.1. Synthesis of **1e**

McMurry coupling reaction was used to prepare alkene **1e** (Scheme 1). The reaction of a 1/1 mixture of ethyl 4-ferrocenyl-4-oxo-butanoate **3** [18] and the commercially available 4,4'-dihydroxybenzophenone **4**, in the presence of zinc and TiCl₄ in THF, gave the expected product in a moderate yield of 51%, despite the possibility of formation of homo-coupling products. Indeed, homo-coupling of the precursors is a known limiting factor for the McMurry coupling reaction. If one of the ketones is more reactive than the other, its homo-coupling can be troublesome, since it leads to its fast disappearance. The remaining second ketone eventually undergoes homo-coupling. We observed that the homo-coupling of 4,4'-dihydroxybenzophenone **4** is quite slow, in contrast to ferrocenyl-alkyl-ketones. Thus, using an excess of **4** appeared to be the best choice to favor the expected coupling. Moving from a 1/1 to a 1/1.5 ratio of **3** and **4** increased the yield of **1e** to 77%. The homo-coupling of
excess **4** giving a tetraphenolic alkene molecule was probable, as assumed by the presence of a solid, insoluble in dichloromethane during workup. Compound **1e** was purified by flash chromatography on silica gel using a mixture of ethyl acetate and cyclohexane (1/2) as the eluent.

<figure><img src="image_4.png" /><figcaption>**Scheme 1.** Synthesis of compound **1e**.</figcaption></figure>

The structure of ester **1e** was established from several classical methods such as ¹H NMR (Figure S1), COSY (Figure S2), ¹³C NMR (Figure S3), DEPT135 (Figure S4), mass spectrometry (Figures S5–S7), and infrared spectroscopy (Figure S8). The low resolution mass spectrum of **1e** (70 eV electronic impact, Figure S5) gave some interesting structural information such as fragments (M-OEt)⁺, (M-Cp)⁺, (M-C₆H₄OH)⁺ that are characteristic of the compound. One can also observe the typical (CpFe)⁺ fragment, common to most ferrocenic compounds. In addition, the solid-state structure of **1e** was determined by XRD.

## 2.2. X-Ray Crystal Structure Determination of **1e**

Suitable crystals of **1e** for XRD analysis (Figure 2) were grown by slow evaporation at room temperature of a solution of **1e** in ethanol/water (approximately 4/1 vol./vol.). Under these conditions, the compound crystallized in the *P*1̄ space group (triclinic system). Only one molecule of **1e** is present in the asymmetric unit and no solvent molecules were present inside. Crystallographic and refinement structure data of **1e** are provided in Table 1. An informative table of crystallographic data for previously published compounds containing an alkyl (1a) (CCDC 739363), an ester (1c) (CCDC 1007086) and (1d) (CCDC 2422842 [19]), or an alcohol (1h) (CCDC 1031238) and (1i) (CCDC 1052065)) moiety on C2 can be found in SI (Table S1).

<figure><img src="image_5.png" /><figcaption>**Figure 2.** Crystal structure of **1e** (CCDC 2426552). Ellipsoids are drawn with 30% probability. Non-polar hydrogen atoms are omitted for the sake of clarity. Only H atoms involved in H bonds are shown; they are depicted in a “ball” mode. Atoms colors: grey (carbon), red (oxygen), orange (iron), and white (hydrogen). C1–C2 bond length at 200 K: 1.3575(22) Å.</figcaption></figure>
<table><caption>**Table 1.** Crystallographic and refinement structure data for **1e**.</caption><thead><tr><th>Parameter</th><th>Value</th><th>Parameter</th><th>Value</th></tr></thead><tbody><tr><td>CCDC deposit number</td><td>2426552</td><td>Crystal size (mm³)</td><td>0.23 × 0.08 × 0.07</td></tr><tr><td>Empirical formula <sup>a</sup></td><td>C<sub>29</sub>H<sub>28</sub>FeO<sub>4</sub></td><td>Wavelength λ (Å)</td><td>1.54178</td></tr><tr><td>Moiety formula</td><td>C<sub>29</sub>H<sub>28</sub>FeO<sub>4</sub></td><td>2θ range (°)</td><td>7.2–133.98</td></tr><tr><td>Formula weight (g/mol)</td><td>496.388</td><td></td><td></td></tr><tr><td>Temperature (K)</td><td>200</td><td>Miller indices ranges</td><td>−10 ≤ h ≤ 11, −13 ≤ k ≤ 13, −15 ≤ l ≤ 15</td></tr><tr><td>Crystal system</td><td>Triclinic</td><td>Measured reflections</td><td>18,999</td></tr><tr><td>Space group</td><td>P<span style="text-decoration: overline">1</span></td><td>Unique reflections</td><td>4413</td></tr><tr><td>a (Å)</td><td>9.5599(3)</td><td>R<sub>int</sub>/R<sub>sigma</sub></td><td>0.0437/0.0332</td></tr><tr><td>b (Å)</td><td>11.2459(4)</td><td>Reflections [I ≥ 2σ(I)]</td><td>3843</td></tr><tr><td>c (Å)</td><td>13.3652(4)</td><td>Restraints</td><td>2</td></tr><tr><td>α (°)</td><td>67.299(2)</td><td>Parameters</td><td>419</td></tr><tr><td>β (°)</td><td>87.272(2)</td><td>Goodness of fit F<sup>2</sup></td><td>1.010</td></tr><tr><td>γ (°)</td><td>70.734(2)</td><td></td><td></td></tr><tr><td>Volume (Å<sup>3</sup>)</td><td>1246.08(8)</td><td>Final R indices <sup>bc</sup> [all data]</td><td>R1 = 0.0338, wR2 = 0.0591</td></tr><tr><td>Z</td><td>2</td><td>Final R indices <sup>bc</sup></td><td>R1 = 0.0267, wR2 = 0.0569</td></tr><tr><td>ρ<sub>calc</sub> (g/cm<sup>3</sup>)</td><td>1.323</td><td>[I ≥ 2σ(I)]</td><td></td></tr><tr><td>Absorption coefficient μ (mm<sup>−1</sup>)</td><td>5.110 (CuKα)</td><td>Largest diff. peak/hole (e/Å<sup>3</sup>)</td><td>0.22/−0.20</td></tr><tr><td>F(000)</td><td>519.6</td><td></td><td></td></tr></tbody></table>

The C1–C2 bond length is 1.36 Å, corresponding to a double bond. Two different intermolecular hydrogen bonds, involving each phenol group, are present in the cell and contribute to the crystal cohesion. The first phenol group (O3) is connected to the second phenol group (O4) of a neighboring molecule (symmetry codes: x, y − 1, z), obtained by a translation of −1 along the b axis (Figure 3). The other (O4) is connected to the carbonyl (O1) of the ester group of another neighboring molecule (symmetry codes: x + 1, y, z), obtained by a translation of 1 along a axis. H bond lengths and angles are shown in Table 2.

<figure><img src="image_6.png" /><figcaption>**Figure 3.** Network of hydrogen bonds in the crystal structure of **1e**. Only hydrogen atoms involved in H bonds are depicted for clarity. H bonds are shown by light green dotted lines. For the central molecule, ellipsoids are drawn with 50% probability and H atoms are shown in “ball” mode. The neighboring molecules involved in H bonds with the central molecule are shown in “capped sticks” mode. Atoms colors: grey (carbon), red (oxygen), orange (iron) and white (hydrogen).</figcaption></figure>

<footnote><sup>a</sup> Including solvent molecules (when present); <sup>b</sup> R1 = $\sum|F_o| - |F_c|/\sum|F_o|$; <sup>c</sup> wR2 = $\sqrt{\sum(w(F_o^2 - F_c^2))/\sum(w(F_o^2))^2}$.</footnote>
<table><caption>**Table 2.** H bond lengths and angles in the crystal structure of 1e at 200 K.</caption><thead><tr><th>D-H...A</th><th>D-H (Å)</th><th>H...A (Å)</th><th>D...A (Å)</th><th>D-H...A (°)</th></tr></thead><tbody><tr><td>O3-H3...O4<sup>i</sup></td><td>0.96(4)</td><td>1.86(4)</td><td>2.808(2)</td><td>172(4)</td></tr><tr><td>O4-H4...O1<sup>ii</sup></td><td>0.92(4)</td><td>1.78(4)</td><td>2.684(2)</td><td>170(4)</td></tr></tbody></table>

D-H: donor atom; H: hydrogen atom; A: acceptor atom. Symmetry codes: (i) x, y − 1, z; (ii) x + 1, y, z.

Crystal structure is also stabilized by Van der Waals-type weak interactions (CH...O and CH...C), including a CH...O interaction between C19–H19 of phenol group and O1 of the carbonyl moiety of a neighboring molecule (symmetry codes: −x + 1, −y + 1, −z + 1), obtained by the inversion center located in the center of the cell.

# 3. Materials and Methods

## 3.1. General Procedure

¹H and ¹³C-NMR spectra were acquired using Bruker 300 and 400 MHz spectrometers (Bruker France, Wissembourg, France, s = singlet; d = doublet; t = triplet; q = quadruplet, m = multiplet). EI-MS was performed using a Nermag R 10-10C spectrometer; ESI-MS using a triple quadrupole mass spectrometer API 3000 LC–MS/MS system (Applied Biosystems, Sciex, Framingham, MA, USA) in positive-ion mode; and high-resolution mass spectrometry (HRMS) using a Jeol MS 7000 instrument (JEOL Europe SAS, Croissy-sur-Seine, France). IR spectra were recorded on an FT-IR spectrometer (Tensor 27, Bruker France, Wissembourg, France) equipped with an ATR MIRacle accessory (Pike Technologies Inc., Madison, WI, USA). Elemental analyses were performed at the microanalysis laboratory of ICSN (Gif sur Yvette, France). Thin-layer chromatography was performed on silica gel 60 GF254 (Merck KGaA, Darmstadt, Germany). Prepacked silica gel columns were obtained from Grace (Grace, Columbia, MD, USA). Flash chromatography was performed using a PuriFlash XS520plus apparatus (Interchim, Montluçon, France). Reagents were obtained from Sigma Aldrich (Saint-Quentin-Fallavier, France) and used as received.

## 3.2. Synthesis of Ethyl 4-En-4-ferrocenyl-5,5-bis-(4-hydroxyphenyl)-pentanoate (1e)

Titanium tetrachloride (CAS 7550-45-0, TiCl₄, 7.7 mL, 70 mmol) was added dropwise to a suspension of zinc powder (CAS 7440-66-6, 8 g, 122 mmol) in dry THF (300 mL). The dark grey mixture obtained was heated at reflux for 2 h. A solution of THF (50 mL) containing 4,4'-dihydroxybenzophenone 4 (CAS 611-99-4, 5.63 g, 26.3 mmol) and ethyl 4-ferrocenyl-4-oxo-butanoate 3 ([18], 5.5 g, 17.5 mmol) was added dropwise to the first solution and the resulting mixture was heated overnight. After cooling to room temperature, the mixture was poured into water and then acidified by the addition of diluted hydrochloric solution until disappearance of the black color. The aqueous layer was extracted with dichloromethane three times. The combined organic layer was dried over MgSO₄ and evaporated. The residue was purified by column chromatography on silica gel (prepacked column and automatic flash chromatography apparatus), eluting with cyclohexane/ethyl acetate (2:1) to give ethyl 4-en-4-ferrocenyl-5,5-bis-(4-hydroxyphenyl)-pentanoate 1e that crystallized during concentration as an orange solid (6.67 g), yield: 77%.

¹H NMR (acetone-d₆): δ 1.17 (t, J = 7.2 Hz, 3H, CH₃), 2.40 (t, J = 8.2 Hz, 2H, CH₂), 2.94 (t, J = 8.2 Hz, 2H, CH₂), 3.95 (t, J = 1.9 Hz, 2H, C₅H₄), 4.03 (q, J = 7.2 Hz, 2H, CH₂O), 4.08 (t, J = 1.9 Hz, 2H, C₅H₄), 4.14 (s, 5H, Cp), 6.71 (d, J = 8.7 Hz, 2H, C₆H₄), 6.83 (d, J = 8.7 Hz, 2H, C₆H₄), 6.87 (d, J = 8.7 Hz, 2H, C₆H₄), 7.08 (d, J = 8.7 Hz, 2H, C₆H₄), 8.22 (s, 1H, OH), 8.28 (s, 1H, OH). ¹³C NMR (acetone-d₆): δ 14.5 (CH₃), 30.9 (CH₂), 35.3 (CH₂), 60.5 (OCH₂), 68.8 (2CH C₅H₄), 69.85 (5CH Cp), 69.93 (2CH C₅H₄), 88.1 (C C₅H₄), 115.7 (2CH C₆H₄), 116.0 (2CH C₆H₄), 131.2 (2CH C₆H₄), 131.7 (2CH C₆H₄), 133.5 (C), 136.6 (C), 137.1 (C), 140.2 (C), 156.76 (C-OH), 156.80 (C-OH), 173.3 (COO). IR (KBr, ν cm⁻¹): 3330, 3396 (OH), 1690 (C=O).
MS (EI, 70 eV) *m/z*: 496 [M]$^+$, 451 [M-OEt]$^+$, 431 [M-Cp]$^+$, 403 [M-C$_6$H$_4$OH]$^+$, 121 [FeCp]$^+$. HRMS (EI, 70 eV, C$_{29}$H$_{28}$FeO$_4$: [M]$^+$) calcd: 496.1337, found: 496.1331. Anal. Calcd for C$_{29}$H$_{28}$FeO$_4$: C, 70.17; H, 5.68. Found: C, 69.89; H, 5.66.

### 3.3. X-Ray Diffraction Experiment

A single crystal of **1e** was selected, mounted onto a cryoloop, and transferred into a cold nitrogen gas stream. Intensity data were collected with a Bruker Kappa-APEXII CCD diffractometer using a micro-focused CuKα radiation. Data collection, unit-cell parameter determination, integration, and data reduction were performed with the Bruker APEX/SAINT [20] suite at 200K. The structure was solved with SHELXT [21] and refined anisotropically by the full-matrix least-squares methods with SHELXL [22], using Olex2 1.5 [23] software (except H atoms). The Olex2.refine [24] software enables the use of ORCA 5.0 [25] quantum chemistry software, using the NoSpherA2 [26] (part of Olex2 1.5 program) tool to improve electron density simulations. Thus, the positions of the hydrogen atoms were freely refined. The structure was deposited at the Cambridge Crystallographic Data Centre with number CCDC 2426552 and can be obtained free of charge via www.ccdc.cam.ac.uk (accessed on 12 March 2025).

**Supplementary Materials:** The following supporting information can be downloaded online. Figure S1. 1H NMR of compound **1e** in acetone-d6; Figure S2. COSY (1H-1H 2D NMR) of compound **1e** in acetone-d6; Figure S3. 13C NMR of compound **1e** in acetone-d6; Figure S4. Stacking of 13C NMR + DEPT135 of compound **1e**; Figure S5. Low resolution mass spectrum of compound **1e**; Figure S6. Zoomed-in view of the HRMS spectra of **1e** (m/z: range 450-550); Figure S7. Formula determination of compound **1e** by HRMS; Figure S8. Infrared spectrum of compound **1e** (ATR); Table S1. Crystallographic data for **1a**, **1c**, **1d**, **1e**, **1h** and **1i**.

**Author Contributions:** Acquisition of X-ray structures and refinement, CCDC deposit (in 2025), J.F.; experimental synthetic work and NMR interpretation, P.P.; conceptualization, P.P.; methodology, J.F. and P.P.; validation, J.F. and P.P.; formal analysis, J.F. and P.P.; investigation, P.P.; data curation, J.F. and P.P.; writing—original draft preparation, J.F. and P.P.; writing—review and editing, J.F. and P.P.; visualization, P.P. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by the Agence Nationale de la Recherche (ANR) under grant number ANR-06-BLAN-0384-01, "FerVect". We thank the Fédération de Recherche de Chimie Moléculaire de Paris Centre (FR2769) for providing technical access to analytical instruments.

**Data Availability Statement:** The data are contained within this article and the Supplementary Materials.

**Acknowledgments:** The authors thank Michèle Salmain, Serge Thorimbert and Geoffrey Gontard for checking/correcting this manuscript.

**Conflicts of Interest:** The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

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# Ethyl 4-ene-4-ferrocenyl-5,5-bis-(4-hydroxyphenyl)-pentanoate

Jérémy Forté<fnref n="1" /> and Pascal Pigeon<fnref n="1" />,<fnref n="2" />*

## Summary

**Figure S1.** ¹H NMR of compound **1e** in acetone-*d*<sub>6</sub> page 2

**Figure S2.** COSY (¹H – ¹H 2D NMR) of compound **1e** in acetone-*d*<sub>6</sub> page 3

**Figure S3.** ¹³C NMR of compound **1e** in acetone-*d*<sub>6</sub> page 4

**Figure S4.** Stacking of ¹³C NMR + DEPT135 of compound **1e** page 5

**Figure S5.** Low resolution mass spectra of compound **1e** page 6

**Figure S6.** Zoomed-in view of the HRMS spectra of **1e** (m/z: range 450 - 550) page 7

**Figure S7.** Formula determination of compound **1e** by HRMS page 8

**Figure S8.** Infrared spectra of compound **1e** (ATR) page 9

**Table S1.** Crystallographic data for **1a**, **1c**, **1d**, **1e**, **1h** and **1i** page 10

<footnote n="1">¹ Institut Parisien de Chimie Moléculaire (IPCM), CNRS, Sorbonne Université, 4 Place Jussieu, F-75005 Paris, France; jeremy.forte@sorbonne-universite.fr</footnote>

<footnote n="2">² Chimie ParisTech, PSL, 11 Rue Pierre et Marie Curie, F-75005 Paris, France</footnote>

<footnote>* Correspondence: pascal.pigeon@sorbonne-universite.fr or pascal.pigeon@chimieparistech.psl.eu</footnote>
<figure><img src="image_7.png" /><figcaption>**Figure S1.** ¹H NMR of compound **1e** in acetone-*d*₆</figcaption></figure>
<figure><img src="image_8.png" /><figcaption>**Figure S2.** COSY (¹H – ¹H 2D NMR) of compound **1e** in acetone-*d*₆</figcaption></figure>
<figure><img src="image_9.png" /><figcaption>**Figure S2.** ¹³C NMR of compound **1e** in acetone-d₆</figcaption></figure>
<figure><img src="image_10.png" /><figcaption>**Figure S3.** Stacking of ¹³C NMR + DEPT135 of compound 1e</figcaption></figure>

The DEPT135 experiment is drawn in blue: CH₂ at 30.9, 35.3 and 60.5 ppm became negative. Quaternary carbon atoms disappeared (88.1, 133.5, 136.6, 137.1, 140.2, 156.76 and 156.80 ppm). CH₃ and CH remained positive.
File: EIP49

Date Run: 02/02/07

Time Run: 15:23:06

Scan: 19 - 21 (-1 - 17)

R.T.: 0:16

Base: m/z 43; 1.7%FS TIC: 15603

PIGEON Pascal Réf P49 EI-FILAMENT 70eV

<figure><img src="image_11.png" /><figcaption>**Figure S4.** Low resolution mass spectra of compound 1e</figcaption></figure>

000060
<figure><img src="image_12.png" /><figcaption>**Figure S5.** Zoomed-in view of the HRMS spectra of **1e** (m/z: range 450 - 550)</figcaption></figure>
[ Elemental Composition ]

Data : PIGEON-P49-EI+-HR001

Sample: -

Note : -

Inlet : Direct

RT : 3.94 min

Elements : C 40/20, H 60/20, O 4/2, Fe 1/1

Mass Tolerance : 10ppm, 10mmu if m/z < 1000, 20mmu if m/z > 2000

Unsaturation (U.S.) : -0.5 - 30.0

Observed m/z Int% Err[ppm / mmu] U.S. Composition
496.1331 100.0 -1.3 / -0.6 16.5 C 29 H 28 O 4 Fe

Date : 07-Feb-2007 11:49

Ion Mode : DEI+

Scan#: (34,37)

Theoretical Ion Distribution ]

Molecular Formula : C29 H28 Fe O4

(m/z 496.1337, MW 496.3859, U.S. 16.5)

Base Peak : 496.1337, Averaged MW : 496.3874(a), 496.3887(w)

m/z      INT.
494.1384  6.2996 ****
495.1418  2.0680 *
496.1337 100.0000 *****************************
497.1369  35.1425 ***************************
498.1395  7.0816 ****
499.1420  1.0359 *
500.1444  0.1204
501.1468  0.0117
502.1491  0.0010

Page: 1

<caption>**Figure S6.** Formula determination of compound **1e** by HRMS</caption>
<figure><img src="image_13.png" /><figcaption>**Figure S8.** Infrared spectra of compound **1e** (ATR)</figcaption></figure>
<table><caption>Table S1. Crystallographic data for 1a, 1c, 1d, 1e, 1h and 1i.</caption><thead><tr><th></th><th>1a</th><th>1c</th><th>1d</th></tr></thead><tbody><tr><td>CCDC deposit number</td><td>739363 (SUHMUE)</td><td>1007086 (TULFAJ)</td><td>2422842 (CUKNIJ)</td></tr><tr><td>Empirical formula<sup>a</sup></td><td>C<sub>26</sub>H<sub>24</sub>FeO<sub>2</sub></td><td>C<sub>28</sub>H<sub>26</sub>FeO<sub>4</sub></td><td>C<sub>29.33</sub>H<sub>30.92</sub>FeO<sub>5.2</sub></td></tr><tr><td>Moiety Formula</td><td>C<sub>26</sub>H<sub>24</sub>FeO<sub>2</sub></td><td>C<sub>28</sub>H<sub>26</sub>FeO<sub>4</sub></td><td>C<sub>28</sub>H<sub>26</sub>FeO<sub>4</sub>,<br>0.533(H<sub>2</sub>O),<br>0.667(C<sub>2</sub>H<sub>6</sub>O)</td></tr><tr><td>Formula weight (g/mol)</td><td>424.313</td><td>482.349</td><td>522.51</td></tr><tr><td>Temperature (K)</td><td>100</td><td>200</td><td>200</td></tr><tr><td>Crystal system</td><td>Triclinic</td><td>Triclinic</td><td>Triclinic</td></tr><tr><td>Space group</td><td>P<span style="text-decoration: overline">1</span></td><td>P<span style="text-decoration: overline">1</span></td><td>P<span style="text-decoration: overline">1</span></td></tr><tr><td>a (Å)</td><td>8.8583(8)</td><td>9.4648(9)</td><td>9.4678(4)</td></tr><tr><td>b (Å)</td><td>10.2256(10)</td><td>11.2957(13)</td><td>18.8145(9)</td></tr><tr><td>c (Å)</td><td>12.0578(11)</td><td>11.9089(16)</td><td>22.9199(11)</td></tr><tr><td>α (°)</td><td>71.964(2)</td><td>90.915(9)</td><td>105.426(3)</td></tr><tr><td>β (°)</td><td>71.182(2)</td><td>92.106(7)</td><td>101.681(3)</td></tr><tr><td>γ (°)</td><td>88.455(2)</td><td>108.490(7)</td><td>93.861(2)</td></tr><tr><td>Volume (Å<sup>3</sup>)</td><td>979.801</td><td>1206.147</td><td>3822.3(3)</td></tr><tr><td>Z</td><td>2</td><td>2</td><td>6</td></tr><tr><td>ρ<sub>calc</sub> (g/cm<sup>3</sup>)</td><td>1.438</td><td>1.328</td><td>1.362</td></tr></tbody></table>

<table><thead><tr><th></th><th>1e</th><th>1h</th><th>1i</th></tr></thead><tbody><tr><td>CCDC deposit number</td><td>2426552</td><td>1031238 (GUCRON)</td><td>1052065 (MUSFIR)</td></tr><tr><td>Empirical formula<sup>a</sup></td><td>C<sub>29</sub>H<sub>28</sub>FeO<sub>4</sub></td><td>C<sub>26</sub>H<sub>24</sub>FeO<sub>3</sub></td><td>C<sub>27</sub>H<sub>26</sub>FeO<sub>3</sub></td></tr><tr><td>Moiety Formula</td><td>C<sub>29</sub>H<sub>28</sub>FeO<sub>4</sub></td><td>C<sub>26</sub>H<sub>24</sub>FeO<sub>3</sub></td><td>C<sub>27</sub>H<sub>26</sub>FeO<sub>3</sub></td></tr><tr><td>Formula weight (g/mol)</td><td>496.388</td><td>440.312</td><td>454.339</td></tr><tr><td>Temperature (K)</td><td>200</td><td>200</td><td>200</td></tr><tr><td>Crystal system</td><td>Triclinic</td><td>Monoclinic</td><td>Monoclinic</td></tr><tr><td>Space group</td><td>P<span style="text-decoration: overline">1</span></td><td>P<sub>2</sub><sub>1</sub>/c</td><td>P<sub>2</sub><sub>1</sub>/c</td></tr><tr><td>a (Å)</td><td>9.5599(3)</td><td>9.9877(4)</td><td>9.2061(2)</td></tr><tr><td>b (Å)</td><td>11.2459(4)</td><td>20.7297(8)</td><td>22.7012(5)</td></tr><tr><td>c (Å)</td><td>13.3652(4)</td><td>10.6135(4)</td><td>10.5180(2)</td></tr><tr><td>α (°)</td><td>67.299(2)</td><td>90</td><td>90</td></tr><tr><td>β (°)</td><td>87.272(2)</td><td>108.554(1)</td><td>103.107(1)</td></tr><tr><td>γ (°)</td><td>70.734(2)</td><td>90</td><td>90</td></tr><tr><td>Volume (Å<sup>3</sup>)</td><td>1246.08(8)</td><td>2083.227</td><td>2140.886</td></tr><tr><td>Z</td><td>2</td><td>4</td><td>4</td></tr><tr><td>ρ<sub>calc</sub> (g/cm<sup>3</sup>)</td><td>1.323</td><td>1.404</td><td>1.41</td></tr></tbody></table>

<footnote><sup>a</sup> Including solvent molecules (if presence)</footnote>

<footnote><sup>a</sup> Including solvent molecules (if presence)</footnote>