# Original Synthesis of Fluorenyl Alcohol Derivatives by Reductive Dehalogenation Initiated by TDAE

Alain Gamal Giuglio-Tonolo, Thierry Terme, Patrice Vanelle

► To cite this version:

Alain Gamal Giuglio-Tonolo, Thierry Terme, Patrice Vanelle. Original Synthesis of Fluorenyl Alcohol Derivatives by Reductive Dehalogenation Initiated by TDAE. Molecules, 2016, 21 (10), 10.3390/molecules21101408. [https://doi.org/10.3390/molecules21101408](https://doi.org/10.3390/molecules21101408)

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Communication

# Original Synthesis of Fluorenyl Alcohol Derivatives by Reductive Dehalogenation Initiated by TDAE

Alain Gamal Giuglio-Tonolo, Thierry Terme and Patrice Vanelle *

Aix-Marseille Université, CNRS, Institut de Chimie Radiculaire ICR, UMR 7273, Laboratoire de Pharmaco-Chimie Radiculaire, Marseille 13385, France; gamal.giuglio-tonolo@univ-amu.fr (A.G.G.-T.); thierry.terme@univ-amu.fr (T.T.)

* Correspondence: patrice.vanelle@univ-amu.fr; Tel.: +33-4-9183-5580; Fax: +33-4-9179-4677

Academic Editor: Derek J. McPhee

Received: 19 September 2016; Accepted: 19 October 2016; Published: 24 October 2016

**Abstract:** We report here a novel and easy-to-handle reductive dehalogenation of 9-bromofluorene in the presence of arylaldehydes and dicarbonyl derivatives to give the corresponding fluorenyl alcohol derivatives and Darzens epoxides as by-products in tetrakis(dimethylamino)ethylene (TDAE) reaction conditions. The reaction is believed to proceed via two successive single electron transfers to generate the fluorenyl anion which was able to react with different electrophiles. A mechanistic study was conducted to understand the formation of the epoxide derivatives.

**Keywords:** tetrakis(dimethylamino)ethylene; reductive dehalogenation; single electron transfer

## 1. Introduction

Fluorenyl derivatives have attracted interest from synthetic organic chemists due to their notable biological and pharmaceutical properties and applications. The literature reports that fluorenone Schiff base derivatives have a potential application and biological activity in therapeutic areas, such as antifungal agents [1,2]. The fluorene skeleton is found in numerous natural products. Dendroflorin and structurally-related nabilone displayed higher antioxidant activity than vitamin C in the ORAC assay [3]. Gramniphenols were isolated from the whole plant of *Arundina graminifolia* by Yang and coworkers in 2012 and displayed anti-HIV-1 activity with therapeutic index values above 100:1 [4]. Many dermatological and photostable cosmetic compositions consist of lumefantrine, a 9-fluorenylidene derivative [5]. The fluorenyl core can be found in indecainide (Decabid®), which is a class Ic anti-arrhythmic agent [6].

In terms of non-steroidal anti-inflammatory agents (NSAIDs), this scaffold bearing an alkanoic acid moiety gives cicloprofen. Paranyline is used in dispersible formulations of anti-inflammatory agents [7]. However, although these drugs are very effective and abundantly prescribed, they have revealed some gastric or intestinal adverse effect [8]. The representatives containing the fluorenyl scaffold cited above are shown in Figure 1.

Since 2003, our laboratory has been developing original synthetic methods based on neutral, ground-state organic reducing agents [9–14], aimed at preparing new, potentially bioactive compounds [9]. Tetrakis(dimethylamino)ethylene (TDAE), as shown in Figure 1 [15–17], is a powerful tool in modern organic chemistry because it allows reduction under mild conditions. Reduction can occur without the use of organometallics or reactive metals. TDAE shows a single, two-electron oxidation peak at –0.62 V vs. SCE in diméthylformamide (DMF) which means it is about as reducing as zinc metal [18–20]. TDAE can react with activated alkyl halides, such as $CF_3I$, $CF_2Br_2$, and activated benzyl halides, to produce the corresponding carbanions [21–30]. We report herein a valuable synthetic method to generate a 9-bromofluorenyl anion from fluorenyl bromide 1 and on its reaction with a series of carbonyl electrophiles affording the corresponding alcohol derivatives.
<figure><img src="image_2.png" /><figcaption>**Figure 1.** Structures of biological active molecules and TDAE.</figcaption></figure>

## 2. Results and Discussion

It was anticipated that fluorenyl bromide **1** could be a good electron-acceptor, because of its large π-conjugated system. Initially, the reaction of 9-bromofluorene **1** and 4-chlorobenzaldehyde **2a** was investigated as the model system (Scheme 1).

<figure><img src="image_3.png" /><figcaption>**Scheme 1.** Optimization of the reaction of fluorenyl bromide **1** with 4-chlorobenzaldehyde **2a** using TDAE.</figcaption></figure>

We performed the reactions using various aprotic polar solvents. The influence of the quantity of aldehyde **2a** and TDAE was also studied. The results are summarized in Table 1.

<table><caption>**Table 1.** Reactions of fluorenyl bromide **1** and aldehyde **2a** with TDAE under various conditions.</caption><thead><tr><th>Entry</th><th>Aldehyde 2a (eq.)</th><th>TDAE (eq.)</th><th>Solvent</th><th>Yield <sup>1,2</sup> of Dimer 3</th><th>Yield <sup>1,2</sup> of 4a</th></tr></thead><tbody><tr><td>1</td><td>2</td><td>1</td><td>DMF</td><td>44%</td><td>29%</td></tr><tr><td>2</td><td>3</td><td>1</td><td>DMF</td><td>8%</td><td>50%</td></tr><tr><td>3</td><td>3</td><td>2</td><td>DMF</td><td>10%</td><td>48%</td></tr><tr><td>4</td><td>4</td><td>1</td><td>DMF</td><td>8%</td><td>46%</td></tr><tr><td>5</td><td>3</td><td>1</td><td>THF</td><td>12%</td><td>48%</td></tr><tr><td>6</td><td>3</td><td>1</td><td>DMF <sup>3</sup></td><td>9%</td><td>56%</td></tr><tr><td>7</td><td>3</td><td>1</td><td>CH<sub>3</sub>CN</td><td>16%</td><td>30%</td></tr><tr><td>8</td><td>3</td><td>1</td><td>DMSO</td><td>20%</td><td>12%</td></tr><tr><td>9</td><td>3</td><td>1</td><td>pyridine</td><td>11%</td><td>34%</td></tr></tbody></table>

A first attempt (entry 1) was carried out with 2 equiv. of **2a** and 1 equiv. of RBr **1** to give 29% of the corresponding alcohol **4a**. TDAE was added at -20 °C to maximize the charge transfer complex formation. Unfortunately, ¹H NMR spectra of the crude product showed a signal at δ 4.85 associated to the homo-coupling adduct of 9-bromofluorene (44%). To reduce the extent of dimer formation,

<footnote n="1">¹ Isolated yields; ² Typical procedure: to a vigorously stirred solution of fluorenyl bromide **1** derivative in 4 mL anhydrous solvent, at -20 °C, under N₂; ³ Moist DMF was used in the presence of a spatula of sodium sulfate in the reaction mixture and the reaction was run under air.</footnote>
3 equiv. of **2a** was employed (entry 2), giving 50% of **4a** and the dimer was isolated with 8% yield (entry 2). The conversion to the 9,9'-bifluorenyl was not reduced by increasing the excess of aldehyde. The optimized protocol of 9-bromofluorene **1** was defined with 3 equiv. of aldehyde **2a**, 1 equiv. of TDAE in DMF, for 1 h at -20 °C followed by 2 h at room temperature. The reactions led to the corresponding alcohol **4a** with 56% yield (Table 1, entry 6). The 9-Bromofluorene was found to be a good substrate in such TDAE-mediated carbon-carbon coupling reactions. This methodology was then applied to other electrophiles. The TDAE-initiated reaction of **1** with various electrophiles was investigated according to the optimal procedure cited above and the results are summarized in Table 2. The expected corresponding alcohols **4a**, **4b**, **4e**, **4f**, **4i** were isolated in moderate to good yields, from 41% to 75% with aldehydes bearing an electron-withdrawing group.

<figure><img src="image_4.png" /><figcaption>**Table 2.** The scope of the reactivity of **1** in the presence of various electrophiles under TDAE reaction conditions.</figcaption></figure>

<table><thead><tr><th rowspan="2">Entry</th><th colspan="2">Electrophiles</th><th rowspan="2">Yield <sup>1,2</sup> of 4</th><th rowspan="2">Yield <sup>1,2</sup> of 5</th></tr><tr><th>R<sub>1</sub></th><th>R<sub>2</sub></th></tr></thead><tbody><tr><td>1</td><td><b>2a</b></td><td>4-ClC<sub>6</sub>H<sub>4</sub></td><td>H</td><td>56% (<b>4a</b>)</td><td>14% (<b>5a</b>)</td></tr><tr><td>2</td><td><b>2b</b></td><td>C<sub>6</sub>H<sub>5</sub></td><td>H</td><td>57% (<b>4b</b>)</td><td>17% (<b>5b</b>)</td></tr><tr><td>3</td><td><b>2c</b></td><td>4-BrC<sub>6</sub>H<sub>4</sub></td><td>H</td><td>75% (<b>4c</b>)</td><td>10% (<b>5c</b>)</td></tr><tr><td>4</td><td><b>2d</b></td><td>4-OMeC<sub>6</sub>H<sub>4</sub></td><td>H</td><td>34% (<b>4d</b>)</td><td></td></tr><tr><td>5</td><td><b>2e</b></td><td>4-FC<sub>6</sub>H<sub>4</sub></td><td>H</td><td>54% (<b>4e</b>)</td><td></td></tr><tr><td>6</td><td><b>2f</b></td><td>4-CNC<sub>6</sub>H<sub>4</sub></td><td>H</td><td>41% (<b>4f</b>)</td><td>30% (<b>5f</b>)</td></tr><tr><td>7</td><td><b>2g</b></td><td>4-MeC<sub>6</sub>H<sub>4</sub></td><td>H</td><td>24% (<b>4g</b>)</td><td></td></tr><tr><td>8</td><td><b>2h</b></td><td>4-(NO<sub>2</sub>)C<sub>6</sub>H<sub>4</sub></td><td>H</td><td></td><td>17% (<b>5h</b>)</td></tr><tr><td>9</td><td><b>2i</b></td><td>4-CF<sub>3</sub>C<sub>6</sub>H<sub>4</sub></td><td>H</td><td>49% (<b>4i</b>)</td><td>6% (<b>5i</b>)</td></tr><tr><td>10</td><td><b>2j</b></td><td>2-furyl</td><td>H</td><td>28% (<b>4j</b>)</td><td>19% (<b>5j</b>)</td></tr><tr><td>11</td><td><b>2k</b></td><td>4-pyridinyl</td><td>H</td><td>42% (<b>4k</b>)</td><td>11% (<b>5k</b>)</td></tr><tr><td>12</td><td><b>2l</b></td><td>3-pyridinyl</td><td>H</td><td>19% (<b>4l</b>)</td><td></td></tr><tr><td>13</td><td><b>2m</b></td><td>Me</td><td>CO<sub>2</sub>Et</td><td>47% (<b>4m</b>)</td><td></td></tr><tr><td>14</td><td><b>2n</b></td><td>CF<sub>3</sub></td><td>CO<sub>2</sub>Me</td><td>41% (<b>4n</b>)</td><td></td></tr><tr><td>15</td><td><b>2o</b></td><td>H</td><td>CO<sub>2</sub>Et</td><td>25% (<b>4o</b>)</td><td></td></tr><tr><td>16</td><td><b>2p</b></td><td>CO<sub>2</sub>Et</td><td>CO<sub>2</sub>Et</td><td>70% (<b>4p</b>)</td><td></td></tr><tr><td>17</td><td><b>2q</b></td><td>C<sub>6</sub>H<sub>5</sub></td><td>Et</td><td></td><td></td></tr></tbody></table>

For 4-nitrobenzaldehyde **2h**, no alcohol product was isolated. Its strong electrophilic character, has already led to unexpected reactivity in these reaction conditions, as cited in our previous work [11]. With methylbenzaldehyde **2g** and 4-methoxybenzaldehyde **2d**, the conversions were lower with, respectively, 24% and 34% yields. This may be explained by their weak electrophilic character compared to the other aldehydes. Competitive epoxide formation was observed, which was obtained in low yield (from 6% to 30%, Table 2, entries 1–9). Subsequently, the methodology was generalized to heteroaromatic aldehydes (entries 10–12). When pyridine-4-carbaldehyde **2k** was employed, 42% of the corresponding alcohol **4k** was obtained. With pyridine-3-carbaldehyde **2l**, the yield reported was lower (19%). The scope of this original reactivity was extended to pyruvates, ethyl glyoxylate, methyl 3,3,3-trifluoropyruvate, and diethylketomalonate (entries 13–16). The best result was achieved with diethylketomalonate affording the corresponding fluorenyl alcohol **4p** in 70% yield (entry 16). This can, no doubt, be attributed to the stronger electrophilic character of its carbonyl function. It should be noted that we never observed the reaction of the fluorenyl anion with ester moiety. The poor yield

<footnote n="1">¹ Isolated yields; ² Typical procedure: to a vigorously-stirred solution of 9-bromofluorene **1** in 4 mL moist DMF with a spatula of sodium sulfate, under air, TDAE was slowly added at -20 °C. The solution was then stirred 1 h at this temperature followed by 2 h at ambient temperature.</footnote>
(19%) observed with ethyl glyoxylate **2o** could be due to a polymerization reaction of the aldehyde. With propriophenone **2q**, only starting materials were recovered (entry 17), which could be attributed to the acidity of the protons adjacent to the carbonyl function.

In order to extend the substrate scope of TDAE-initiated reactions, an attempt had been run with 1,1'-bromobiphenylmethane, but no alcohol adduct was formed. The corresponding dimer product was obtained with 74% yield. This difference in reactivity can be attributed to the better stabilization of the corresponding 9-fluorenyl aromatic anion.

The formation of the alcohol product can be conceived to proceed via two successive single electron transfers (Scheme 2). The first reduction leads to the cleavage of the C-Br bond to form the 9-fluorenyl radical and the bromide anion. A subsequent SET (single monoelectronic transfer) gave the fluorenyl anion A, which is aromatic and has an intense orange color, from the corresponding radical. An alcoholate was successively obtained by the nucleophilic addition of the fluorenyl anion A on the aldehyde which gave the corresponding alcohol after hydrolysis. As cited above, 9-bromofluorene 1 can react under our conditions with aromatic aldehydes, yielding epoxy products. Our hypothesis is that 9-bromofluorenyl anion B could be formed after deprotonation of 1 by the above alcoholate. The reaction of B with the aldehyde gave the epoxide derivatives via Darzen reaction. Our hypothesis is supported by literature data [31].

<figure><img src="image_5.png" /><figcaption>**Scheme 2.** Proposed mechanism.</figcaption></figure>

When 9-bromofluorene **1** was treated with 3 equiv. of triethylamine in the presence of 4-cyanobenzaldehyde **2f** under classical TDAE conditions, the corresponding Darzens condensation product **5f** was afforded in low yields (7%) (Scheme 3).

<figure><img src="image_6.png" /><figcaption>**Scheme 3.** Reactivity of 9-bromofluorene and 4-cyanobenzaldehyde in the presence of trimethylamine.</figcaption></figure>

Another compound had been observed by ¹H-NMR corresponding to 4-((9H-fluoren-9-ylidene) methyl)benzonitrile **6f** with 15% yield. However, another multistep pathway involving a carbene-like intermediate cannot be excluded. To verify this hypothesis, we examined the reaction of **1** in
the presence of cyclohexene [32]. The ¹H-NMR spectrum of the crude mixture showed no signal attributable to a cyclopropane adduct that could formed by carbene insertion to the cyclohexene double bond: only peaks due to dimer **3** were found. These findings indicate that the epoxide derivative could be formed through the 9-bromofluorenyl anion sequence.

# 3. Materials and Methods

## 3.1. General Information

Melting points were determined on a Büchi melting point B-540 apparatus (BÜCHI Labortechnik AG, Flawil, Switzerland) and are uncorrected. Element analyses were performed on a Thermo Finnigan EA1112 (San Jose, CA, USA) at the spectropole of the Aix-Marseille University. Both ¹H- and ¹³C-NMR spectra were determined on a Bruker Avance 250 spectrometer (Wissembourg, France) at the Service de RMN de la Faculté de Pharmacie de Marseille of the Aix-Marseille University and on a Bruker Avance III NanoBay 300 MHz spectrometer at the spectropole of Aix-Marseille University. The ¹H- and the ¹³C-chemical shifts are reported from CDCl₃ peaks: ¹H (7.26 ppm) and ¹³C (77 ppm) or Me₂SO-d₆ (39.6 ppm). Multiplicities are represented by the following notations: s, singlet; d, doublet; t, triplet; q, quartet; m, a more complex multiplet, or overlapping multiplets. The following adsorbents were used for column chromatography: silica gel 60 (Merck, particle size 0.063–0.200 mm, 70–230 mesh ASTM, (Merck, Darmstadt, Germany). Thin Layer Chromatography (TLC) was performed on 5 cm × 10 cm aluminum plates coated with silica gel 60 F254 (Merck) in an appropriate solvent.

## 3.2. Typical Procedure

The TDAE (0.14 mL, 0.6 mmol) was slowly added, with a syringe, at –20 °C to a vigorously stirred solution of fluorenyl bromide **1** (150 mg, 0.6 mmol) with the appropriate aldehyde (1.8 mmol, 3 equivalents) and a spatula of sodium sulfate in 4 mL of DMF, under air. A red color was immediately developed with the formation of a fine white precipitate. The mixture was then stirred at –20 °C for 1 h and warmed to room temperature over a period of 2 h. Then 0.5 mL of water was added to quench the reaction. The solution was extracted with dichloromethane (3 × 30 mL), the combined organic layers were washed with brine (3 × 40 mL), and dried over MgSO₄. The crude product was then obtained after evaporation of the solvent under reduced pressure. Purification by silica gel chromatographic column (dichloromethane: methanol) gave the corresponding fluorenyl derivatives.

## 3.3. Compound Characterizations

**9H,9'-H-9,9'-Bifluorene:** **3** (9%); yellow powder; m.p. 216–217 °C (Lit.: 237–239 °C). ¹H-NMR (200 MHz) (CDCl₃) 7.66 (d, *J* = 7.51 Hz, 4H); 7.33–7.26 (m, 4H); 7.15–7.07 (m, 4H); 6.97 (d, *J* = 7.34 Hz, 4H); 4.85 (s, 2H). ¹³C-NMR (50 MHz) (CDCl₃) 144.6 (4CIV); 141.5 (4CIV); 127.3 (4CHar); 126.7 (4CHar); 124.0 (4CHar); 119.6 (4CHar); 49.8 (2CH). Physical and spectroscopic data agree with those reported in the literature [33,34].

**(4-Chlorophenyl)(9H-fluoren-9-yl)methanol:** **4a** (56%); yellow powder; m.p. 142–143 °C (Lit.: 126.5 °C). ¹H-NMR (200 MHz) (CDCl₃): 7.70 (d, *J* = 7.5 Hz, 2H); 7.40–7.17 (m, 10H); 5.15 (d, *J* = 5.7 Hz, 1H); 4.37 (d, *J* = 5.7 Hz, 1H); 1.90 (bs, OH). ¹³C-NMR (50 MHz) (CDCl₃): 143.0 (CIV); 142.9 (2CIV); 141.7 (CIV); 140.2 (2CIV); 128.1 (2CHar); 127.7 (2CHar); 126.7 (2CHar); 125.9 (2CHar); 125.5 (2CHar); 119.8 (2CHar); 75.6 (CH); 56.4 (CH). HRMS (ESI⁺): *m/z* [M + Na]⁺ calculated for C₂₀H₁₅OClNa⁺: 329.0704 Da; found: 329.0704 Da. Physical data agree with those reported in the literature [35].

**3'-(4-Chlorophenyl)spiro(fluorene-9,2'-oxirane):** **5a** (14%) yellow powder; m.p. 63–64 °C. ¹H-NMR (200 MHz) (CDCl₃) 7.76–7.68 (m, 2H); 7.51–7.29 (m, 8H); 7.02–6.94 (dd, *J* = 1 and 7.6 Hz, 1H); 6.50 (d, *J* = 7.6 Hz, 1H); 4.91 (s, 1H). ¹³C-NMR (50 MHz) (CDCl₃) 141.6 (CIV); 141.4 (CIV); 140.6 (CIV); 138.4 (CIV); 134.0 (CIV); 133.7 (CIV); 129.4 (CHar); 129.3 (CHar); 128.6 (2CHar); 128.3 (2CHar); 127.6 (CHar).
(2Char); 127.0 (CHar); 123.9 (CHar); 121.6 (CHar); 120.1 (CHar); 67.6 (CIV); 59.1 (CH). HRMS (ESI⁺): *m/z* [M + H]⁺ calculated for C₂₀H₁₄OCl⁺: 305.0728 Da; found: 305.0728 Da.

**(9H-Fluoren-9-yl)(phenyl)methanol:** **4b** (57%); yellow powder; m.p. 116–117 °C (Lit.: 120–121 °C). ¹H-NMR (200 MHz) (CDCl₃) 7.64–7.60 (m, 2H); 7.31–7.24 (m, 7H); 7.16–7.06 (m, 3H); 6.97 (d, *J* = 6.9 Hz, 1H); 5.09 (d, *J* = 6.1 Hz, 1H); 4.40 (d, *J* = 6.1 Hz, 1H); 1.68 (bs, OH). ¹³C-NMR (50 MHz) (CDCl₃) 143.6 (CIV); 143.3 (CIV); 142.1 (CIV); 141.8 (CIV); 141.7 (CIV); 128.1 (2CHar); 127.8 (CHar); 127.6 (CHar); 126.8 (2CHar); 126.7 (CHar); 126.6 (CHar); 126.6 (CHar); 126.2 (CHar); 125.5 (CHar); 119.8 (CHar); 119.7 (CHar); 76.3 (CH); 54.7 (CH). HRMS (ESI⁺): *m/z* [M + Na]⁺ calculated for C₂₀H₁₆ONa⁺: 295.1093 Da; found: 295.1093 Da. Physical and spectroscopic data agree with those reported in the literature [34,36].

**3'-Phenylspiro(fluorene-9,2'-oxirane):** **5b** (17%); yellow powder; m.p. 119–120 °C (Lit.: 130–131 °C). ¹H-NMR (200 MHz) (CDCl₃) 7.76–7.67 (m, 2H); 7.50–7.30 (m, 9H); 6.93 (dt, *J* = 7.6 and 0.9 Hz, 1H); 6.50 (d, *J* = 7.6 Hz, 1H); 4.97 (s, 1H). ¹³C-NMR (50 MHz) (CDCl₃) 141.7 (CIV); 141.5 (CIV); 140.6 (CIV); 138.7 (CIV); 135.2 (CIV); 129.3 (CHar); 129.1 (CHar); 128.3 (2CHar); 128.1 (CHar); 127.6 (CHar); 127.0 (CHar); 126.8 (2CHar); 124.1 (CIV); 121.6 (CHar); 120.2 (CHar); 120.1 (CHar); 67.6 (CIV); 65.7 (CH). HRMS (ESI⁺): *m/z* [M + Na]⁺ calculated for C₂₀H₁₄ONa⁺: 293.0937 Da; found: 293.0936 Da. Physical and spectroscopic data agree with those reported in the literature [37].

**(4-Bromophenyl)(9H-fluoren-9-yl)methanol:** **4c** (75%); yellow powder; m.p. 129–130 °C. ¹H-NMR (200 MHz) (CDCl₃) 7.70 (d, *J* = 7.4 Hz, 2H); 7.43–7.34 (m, 4H); 7.30–7.20 (m, 4H); 7.15 (d, *J* = 8.4 Hz, 2H); 5.15 (d, *J* = 5.5 Hz, 1H); 4.38 (d, *J* = 5.5 Hz, 1H). ¹³C-NMR (50 MHz) (CDCl₃) 143.0 (2CIV); 142.9 (CIV); 141.8 (CIV); 140.8 (2CIV); 131.1 (2CHar); 128.4 (2CHar); 127.7 (CHar); 126.8 (CHar); 126.7 (CHar); 125.9 (CHar); 125.5 (CHar); 121.5 (CHar); 119.9 (CHar); 119.8 (CHar); 75.7 (CH); 54.6 (CH). HRMS (ESI⁺): *m/z* [M + Na]⁺ calculated for C₂₀H₁₅OBrNa⁺: 373.0198 Da; found: 373.0198 Da.

**3'-(4-Bromophenyl)spiro(fluorene-9,2'-oxirane):** **5c** (10%) yellow powder; m.p. 122–123 °C. ¹H-NMR (200 MHz) (CDCl₃) 7.76–7.69 (m, 2H); 7.57–7.54 (m, 2H); 7.51–7.28 (m, 6H); 7.02–6.96 (m, 1H); 7.51 (d, *J* = 7.7 Hz, 1H); 4.86 (s, 1H). ¹³C-NMR (50 MHz) (CDCl₃) 141.6 (CIV); 141.3 (CIV); 140.6 (CIV); 138.2 (CIV); 134.2 (CIV); 131.6 (2CHar); 129.5 (CHar); 129.3 (CHar); 128.6 (2CHar); 127.7 (CHar); 127.1 (CHar); 123.9 (CHar); 122.2 (CIV); 121.6 (CHar); 120.2 (2CHar); 67.6 (CIV); 65.1 (CH). HRMS (ESI⁺): *m/z* [M + H]⁺ calculated for C₂₀H₁₄OBrNa⁺: 349.0223 Da; found: 349.0150 Da.

**(9H-Fluoren-9-yl)(4-methoxyphenyl)methanol:** **4d** (34%); white powder; m.p. 115–116 °C. (Lit.: 122–123 °C)³; ¹H-NMR (200 MHz) (CDCl₃) 7.74–7.70 (dd, *J* = 7.6 and 3.3 Hz, 2H); 7.46–7.32 (m, 3H); 7.27–7.15 (m, 4H); 7.03 (d, *J* = 7.6 Hz, 1H); 6.88 (d, *J* = 8.8 Hz, 2H); 4.97 (d, *J* = 6.5 Hz, 1H); 4.38 (d, *J* = 6.5 Hz, 1H); 3.83 (s, 3H) 1.96 (bs, OH). ¹³C-NMR (50 MHz) (CDCl₃) 159.1 (CIV); 143.9 (CIV); 143.3 (CIV); 141.8 (CIV); 141.6 (CIV); 134.4 (CIV); 128.0 (2CHar); 127.6 (CHar); 127.5 (CHar); 126.6 (CHar); 126.5 (CHar); 126.3 (CHar); 125.7 (CHar); 119.8 (CHar); 119.7 (CHar); 113.5 (2CHar); 76.1 (CH); 55.2 (CH); 54.7 (CH₃). HRMS (ESI⁺): *m/z* [M + Na]⁺ calculated for C₂₁H₁₈O₂Na⁺: 325.1199 Da; found: 325.1200 Da.

**(9H-Fluoren-9-yl)(4-fluorophenyl)methanol:** **4e** (54%); white powder; m.p. 120–121 °C; ¹H-NMR (200 MHz) (CDCl₃) 7.70 (d, *J* = 7.4 Hz, 2H); 7.41–7.33 (m, 3H); 7.26–7.14 (m, 5H); 7.01–6.95 (m, 2H); 5.11 (d, *J* = 5.6 Hz, 1H); 4.37 (d, *J* = 5.6 Hz, 1H); 2.01 (bs, OH). ¹³C-NMR (50 MHz) (CDCl₃) 160.5 (CIV); 143.5 (CIV); 143.2 (CIV); 142.0 (CIV); 141.9 (CIV); 134.8 (CIV); 128.5 (CHar); 128.4 (CHar); 127.7 (2CHar); 126.7 (2CHar); 126.0 (CHar); 125.7 (CHar); 119.9 (CHar); 119.8 (CHar); 115.0 (CHar); 114.7 (CHar); 75.9 (CIV); 54.9 (CH). HRMS (ESI⁺): *m/z* [M + Na]⁺ calculated for C₂₀H₁₅OFNa⁺: 313.0999 Da; found: 313.0999 Da.

**4-((9H-Fluoren-9-yl)(hydroxy)methyl)benzonitrile:** **4f** (41%); white powder; m.p. 169–170 °C; ¹H-NMR (200 MHz) (CDCl₃) 7.68 (d, *J* = 7.7 Hz, 2H); 7.52 (d, *J* = 8.2 Hz, 2H); 7.41–7.18 (m, 8H); 5.36 (d, *J* = 4.7 Hz, 1H); 4.42 (d, *J* = 4.7 Hz, 1H); 2.07 (bs, 1H). ¹³C-NMR (50 MHz) (CDCl₃) 146.7 (CIV); 142.5 (CIV); 142.3 (CIV); 141.8 (2CIV); 131.6 (2CHar); 128.0 (2CHar); 127.3 (2CHar); 127.0 (CHar); 126.8 (CHar); 125.5 (CHar). HRMS (ESI⁺): *m/z* [M + Na]⁺ calculated for C₂₀H₁₅OFNa⁺: 313.0999 Da; found: 313.0999 Da.
(2CHar); 118.9 (2CHar); 73.0 (CH); 63.73 (CH). HRMS (ESI⁺): *m/z* [M − H]⁻ calculated for C₁₉H₁₄NO⁻: 272.1081 Da; found: 272.1081 Da.

4-(Spiro(fluorene-9,2'-oxiran)-3'-yl)pyridine: **5k** (11%); Yellow powder; m.p. 197–198 °C. **¹H-NMR** (200 MHz) (DMSO-d₆) 8.13 (d, *J* = 8.0 Hz, 1H); 7.88 (d, *J* = 7.0 Hz, 2H); 7.36–7.18 (m, 4H); 6.50 (d, *J* = 7.0 Hz, 2H); 6.22 (d, *J* = 5.9 Hz, 1H); 5.83 (d, *J* = 5.9 Hz, 1H). **¹³C-NMR** (50 MHz) (DMSO-d₆) 147.7 (2CHar); 144.4 (2CIV); 143.5 (2CIV); 139.0 (CIV); 129.3 (CHar); 129.2 (CHar); 127.5 (CHar); 127.3 (CHar); 126.7 (CHar); 125.1 (CHar); 122.4 (2CHar); 119.8 (CHar); 119.6 (CHar); 76.9 (CH); 75.6 (CH). HRMS (ESI⁺): *m/z* [M + Na]⁺ calculated for C₁₉H₁₃NONa⁺: 294.0889 Da; found: 294.0891 Da.

(9H-Fluoren-9-yl)(pyridin-3-yl)methanol **4l** (19%); white powder; m.p. 253–254 °C. **¹H-NMR** (200 MHz) (DMSO-d₆) 8.16–8.14 (dd, *J* = 4.7 et 1.7 Hz, 1H); 7.88 (d, *J* = 1.9 Hz, 1H); 7.76–7.73 (m, 1H); 7.56–7.45 (m, 3H); 7.34–7.26 (m, 4H); 7.08–7.04 (dt, *J* = 7.9 et 1.9, 1H); 6.95–6.90 (dd, *J* = 7.7 ou 7.9 et 4.7 Hz, 1H); 6.03 (s, OH); 5.83 (d, *J* = 3.7 Hz, 1H); 5.17 (d, *J* = 3.7 Hz, 1H). **¹³C-NMR** (50 MHz) (DMSO-d₆) 148.4 (CHar); 147.3 (CHar); 146.3 (2CIV); 139.8 (2CIV); 134.2 (CHar); 128.2 (CHar); 128.1 (CHar); 126.7 (2CHar); 126.6 (CIV); 125.6 (CHar); 124.5 (CHar); 121.4 (CHar); 119.2 (CHar); 119.0 (CHar); 83.71 (CH); 76.3 (CH). HRMS (ESI⁺): *m/z* [M + H]⁺ calculated for C₁₉H₁₆NO⁺: 274.1226 Da; found: 274.1226 Da.

Ethyl 2-(9H-fluoren-9-yl)-2-hydroxypropanoate **4m** (47%): orange oil. **¹H-NMR** (200 MHz) (CDCl₃) 7.73 (d, *J* = 7.3 Hz, 2H); 7.63–7.54 (m, 2H); 7.39–7.35 (m, 4H); 4.31 (s, 1H); 4.05 (q, *J* = 7.1 Hz, 2H); 1.60 (s, 3H); 1.04 (t, *J* = 7.1 Hz, 3H). **¹³C-NMR** (50 MHz) (CDCl₃) 175.3 (CIV); 143.0 (CIV); 142.6 (CIV); 142.2 (CIV); 141.8 (CIV); 127.9 (CHar); 127.7 (CHar); 126.7 (2CHar); 126.0 (CHar); 125.7 (CHar); 119.7 (CHar); 119.6 (CHar); 77.2 (CIV); 61.7 (CH₂); 56.0 (CH); 23.9 (CH₃); 13.7 (CH₃). HRMS (ESI⁺): *m/z* [M + NH₄]⁺ calculated for C₁₈H₂₂NO₃⁺: 300.1594 Da; found: 300.1592 Da.

Methyl 2-(9H-fluoren-9-yl)-3,3,3-trifluoro-2-hydroxypropanoate **4n** (41%); yellow powder; m.p. 94–95 °C. **¹H-NMR** (200 MHz) (CDCl₃) 7.77–7.71 (m, 3H); 7.45–7.39 (m, 2H); 7.33–7.25 (m, 3H); 4.61 (s, 1H); 3.70 (s, 3H). **¹³C-NMR** (50 MHz) (CDCl₃) 169.2 (CIV); 142.7 (CIV); 142.1 (CIV); 140.1 (CIV); 139.8 (CIV); 128.5 (CHar); 128.3 (CHar); 126.7 (CHar); 126.8 (2CHar); 125.5 (CHar); 119.8 (CHar); 119.6 (CHar); 80.0 (CIV); 79.5 (CIV); 53.8 (CH); 50.2 (CH₃). HRMS (ESI⁺): *m/z* [M + NH₄]⁺ calculated for C₁₇H₁₇NO₃F₃⁺: 340.1155 Da; found: 340.1157 Da.

Ethyl 2-(9H-fluoren-9-yl)-2-hydroxyacetate **4o** (25%): yellow powder; m.p. 135–136 °C. **¹H-NMR** (200 MHz) (CDCl₃) 7.75 (d, *J* = 7.1 Hz, 2H); 7.65 (m, 1H); 7.43–7.26 (m; 5H); 4.94 (d, *J* = 2.7 Hz, 1H); 4.43 (d, *J* = 2.7 Hz, 1H); 4.08 (q, *J* = 7.1 Hz, 2H); 1.03 (t, *J* = 7.1 Hz, 3H). **¹³C-NMR** (50 MHz) (CDCl₃) 173.2 (CIV); 143.3 (2CIV); 142.2 (2CIV); 127.8 (CHar); 127.7 (CHar); 127.2 (CHar); 127.0 (CHar); 124.7 (CHar); 124.5 (CHar); 119.9 (CIV); 119.8 (CHar); 72.6 (CH); 61.6 (CH); 48.31 (CH₂); 13.7 (CH₃). HRMS (ESI⁺): *m/z* [M + H]⁺ calculated for C₁₇H₁₇O₃⁺: 269.1172 Da; found: 269.1171 Da.

Diethyl 2-(9H-fluoren-9-yl)-2-hydroxymalonate **4p** (70%): white powder; m.p. 75–76 °C. **¹H-NMR** (200 MHz) (CDCl₃) 7.74 (d, *J* = 7.4 Hz, 2H); 7.49 (d, *J* = 7.4 Hz, 2H); 7.43–7.36 (m, 2H); 7.30–7.22 (m, 2H); 4.93 (s, 1H); 4.25 (q, *J* = 7.2 Hz, 4H); 3.88 (bs, 1H); 1.19 (t, *J* = 7.2 Hz, 6H). **¹³C-NMR** (50 MHz) (CDCl₃) 169.5 (2CIV); 142.1 (2CIV); 141.6 (2CIV); 128.0 (2CHar); 127.0 (2CHar); 125.3 (2CHar); 119.7 (2CHar); 81.3 (CIV); 62.6 (2CH₂); 54.6 (CH); 13.7 (2CH₃). HRMS (ESI⁻): *m/z* [M + H]⁺ calculated for C₂₀H₂₁O₅⁺: 341.1384 Da; found: 340.1311 Da.

### 3.4. Reactivity of 9-Bromofluorene and 4-Cyanobenzaldehyde in the Presence of Triethylamine

Triethylamine (150 mg, 1.2 mmol) was added to a stirred solution of fluorenyl bromide **1** (100 mg, 0.5 mmol) with the 4-cyanobenzaldehyde (160 mg, 1.2 mmol) and a spatula of sodium sulfate in 4 mL of DMF, under air. The mixture was then stirred at –20 °C for 1 h and warmed to room temperature over a period of 24 h. Then 0.5 mL of water was added to quench the reaction. The solution was extracted with dichloromethane (3 × 30 mL), the combined organic layers were washed with brine (3 × 40 mL), and dried over MgSO₄. The crude product was then obtained after evaporation of the
solvent under reduced pressure. Purification by silica gel chromatographic column (dichloromethane: methanol) gave the 20% of the unreacted 9-bromofluorene with 15% yield of the 4-((9H-fluoren-9-ylidene)methyl)benzo-nitrile **8c** and 7% yield of the 4-(spiro(fluorene-9,2'-oxiran)-3'-yl)benzonitrile **5f** gave the unreacted 9-bromofluorene (20%) with 4-((9H-fluoren-9-ylidene)methyl)benzonitrile **6f** (15%) and 4-(spiro(fluorene-9,2'-oxiran)-3'-yl)benzonitrile **5f** (7%).

4-((9H-Fluoren-9-ylidene)methyl)benzonitrile: **6f** (15%) yellow powder; m.p. 149–150 °C (Lit.: 150–151). 1H-NMR (200 MHz) (CDCl₃) 7.97–7.94 (m, 1H); 7.75–7.73 (m, 1H); 7.41–7.30 (m, 6H); 7.12 (d, *J* = 8.3 Hz, 2H); 7.12 (d, *J* = 8.3 Hz, 2H); 6.80 (bs, 1H). Physical and spectroscopic data agree with those reported in the literature [38].

**4. Conclusions**

This strategy afforded a novel and convenient synthesis of various 9-fluorenylidene derivatives under mild reaction conditions. TDAE was used to generate the fluorenyl anion in situ and under practical conditions, which could be extended to electrophiles. In this study, TDAE, or another base present in the reaction mixture, was also able to promote the formation of epoxide derivatives. Moreover, because of their structural analogy with recently reported compounds, the anti-nociceptive properties of all intermediates are under active investigation.

**Acknowledgments:** This work is supported by the Centre National de la Recherche Scientifique. We express our thanks to V. Remusat for 1H- and 13C-NMR spectra recording and Valérie Monnier for measured HRMS.

**Author Contributions:** A.G.G.-T., T.T. and P.V. conceived and designed the study. A.G.G.-T. and T.T. designed the experiments and interpreted the results. A.G.G.-T., T.T. and P.V. wrote the manuscript.

**Conflicts of Interest:** The authors declare no conflict of interest.

**References**

1. El-Shekeil, A.; El-Sonbati, A.Z. Fluorenone thiosemicabazone complexes of bivalent metalions. *Transit. Met. Chem. 1992*, *17*, 420–422. [CrossRef]

2. Ahmad, T.; Kandil, F.; Moustapha, C. Synthesis, Characterization, Biological Evaluation and Antibacterial Activity of some Heterocyclic Fluorene Compounds Derived from Schiff Base. *Int. J. ChemTech Res.* **2015**, *8*, 447–458.

3. Zhang, X.; Xu, J.-K.; Wang, J.; Wang, N.-L.; Kurihara, H.; Kitanaka, S.; Yao, X.-S. Bioactive Bibenzyl Derivatives and Fluorenones from *Dendrobium nobile*. *J. Nat. Prod.* **2007**, *70*, 24–28. [CrossRef] [PubMed]

4. Hu, Q.-F.; Zhou, B.; Huang, J.-M.; Gao, X.-M.; Shu, L.-D.; Yang, G.-Y.; Che, C.-T. Antiviral Phenolic Compounds from *Arundina graminifolia*. *J. Nat. Prod.* **2013**, *76*, 292–296. [CrossRef] [PubMed]

5. Mueller, S.; Herzog, B.; Quass, K. Photostable Cosmetic or Dermatological Compositions Containing Sunscreens. PCT International Application WO 2006034968, 6 April 2006.

6. Anonymous. 9-Aminoalkylfluorenes and Their Salts. Austrian Patent AT 368125, 10 September 1982.

7. Britten, N.J.; Burns, J.W.; Hallberg, J.W.; Waldron, N.A.; Watts, J.L. Dispersible Formulations of an Anti-inflammatory Agent. PCT International Application WO 2004082588, 30 September 2004.

8. Laine, L.; Connors, L.G.; Reicin, A.; Hawkey, C.J.; Burgos-Vargas, R.; Schnitzer, T.J.; Yu, Q.; Bombardier, C. Serious lower gastrointestinal clinical events with nonselective NSAID or coxib use. *Gastroenterology* **2003**, *124*, 288–292. [CrossRef] [PubMed]

9. Giuglio-Tonolo, G.; Terme, T.; Médebielle, M.; Vanelle, P. Original reaction of p-nitrobenzyl chloride with aldehydes using tetrakis(dimethylamino)ethylene (TDAE). *Tetrahedron Lett.* **2003**, *44*, 6433–6435. [CrossRef]

10. Giuglio-Tonolo, G.; Terme, T.; Médebielle, M.; Vanelle, P. Nitrobenzylation of α-carbonyl ester derivatives using TDAE approach. *Tetrahedron Lett.* **2004**, *45*, 5121–5124. [CrossRef]

11. Amiri-Attou, O.; Terme, T.; Médebielle, M.; Vanelle, P. Original formation of benzyl benzoates by TDAE strategy. *Tetrahedron Lett.* **2008**, *49*, 1016–1020. [CrossRef]

12. Juspin, T.; Terme, T.; Vanelle, P. TDAE Strategy Using α-Diketones: Rapid Access to 2,3-Diphenylquinoline and Acenaphtho[1,2-**b**]quinoline Derivatives. *Synlett* **2009**, 1485–1489. [CrossRef]
13. Khoumeri, O.; Montana, M.; Terme, T.; Vanelle, P. Rapid and efficient synthesis of 2-substituted-tetrahydropyrido[3,4-*b*]quinoxalines using TDAE strategy. *Tetrahedron Lett.* **2012**, *53*, 2410–2413. [CrossRef]

14. Giuglio-Tonolo, A.G.; Spitz, C.; Terme, T.; Vanelle, P. An expeditious method for the selective cyclotrimerization of isocyanates initiated by TDAE. *Tetrahedron Lett.* **2014**, *55*, 2700–2702. [CrossRef]

15. Juspin, T.; Laget, M.; Terme, T.; Azas, N.; Vanelle, P. TDAE-assisted synthesis of new imidazo[2,1-*b*]thiazole derivatives as anti-infectious agents. *Eur. J. Med. Chem.* **2010**, *45*, 840–845. [CrossRef] [PubMed]

16. Montana, M.; Terme, T.; Vanelle, P. Original synthesis of oxiranes via TDAE methodology: Reaction of 2,2-dibromomethylquinoxaline with aromatic aldehydes. *Tetrahedron Lett.* **2005**, *46*, 8373–8376. [CrossRef]

17. Roche, M.; Lacroix, C.; Khoumeri, O.; Franco, D.; Neyts, J.; Terme, T.; Leyssen, P.; Vanelle, P. Synthesis, biological activity and structure-activity relationship of 4,5-dimethoxybenzene derivatives inhibitor of rhinovirus. *Eur. J. Med. Chem.* **2014**, *76*, 445–459. [CrossRef] [PubMed]

18. Murphy, J.A.; Zhou, S.; Thomson, D.W.; Schoenebeck, F.; Mahesh, M.; Park, S.R.; Tutle, T.; Berlouis, L.E.A. Highly Efficient Reduction of Unactivated Aryl and Alkyl Iodides by a Ground-State Neutral Organic Electron Donor. *Angew. Chem. Int. Ed.* **2005**, *44*, 1356–1360. [CrossRef] [PubMed]

19. Murphy, J.A.; Khan, T.A.; Zhou, S.; Thomson, D.W.; Schoenebeck, F.; Mahesh, M.; Park, S.R.; Tuttle, T.; Berlouis, L.E.A. The Generation of Aryl Anions by Double Electron Transfer to Aryl Iodides from a Neutral Ground-State Organic Super-Electron Donor. *Angew. Chem. Int. Ed.* **2007**, *46*, 5178–5183. [CrossRef] [PubMed]

20. Broggi, J.; Terme, T.; Vanelle, P. Organic Electron Donors as Powerful Single-Electron Reducing Agents in Organic Synthesis. *Angew. Chem. Int. Ed.* **2014**, *53*, 384–413. [CrossRef] [PubMed]

21. Kuroboshi, M.; Waki, Y.; Tanaka, H. Palladium-Catalyzed Tetrakis(dimethylamino)ethylene-Promoted Reductive Coupling of Aryl Halides. *J. Org. Chem.* **2003**, *68*, 3938–3942. [CrossRef] [PubMed]

22. Pawelke, G. Tetrakis(dimethylamino)ethylene/trifluoroiodomethane. A specific novel trifluorome-thylating agent. *J. Fluor. Chem.* **1989**, *42*, 429–433. [CrossRef]

23. Takechi, N.; Aït-Mohand, S.; Médebielle, M.; Dolbier, W.R.J. Nucleophilic trifluoromethylation of acyl chlorides using the trifluoromethyl iodide/TDAE reagent. *Tetrahedron Lett.* **2002**, *43*, 4317–4319. [CrossRef]

24. Pawelke, G. Reaction of tetrakis(dimethylamino)ethylene with CF2Br2 in the presence of secondary amines, formation of N-trifluoromethyl-dialkylamines. *J. Fluor. Chem.* **1991**, *52*, 229–234. [CrossRef]

25. Since, M.; Terme, T.; Vanelle, P. Original TDAE strategy using α-halocarbonyl derivatives. *Tetrahedron* **2009**, *65*, 6128–6134. [CrossRef]

26. Juspin, T.; Giuglio-Tonolo, G.; Terme, T.; Vanelle, P. First TDAE-Mediated Double Addition of Nitrobenzylic Anions to Aromatic Dialdehydes. *Synthesis* **2010**, *5*, 844–848.

27. Pooput, C.; Dolbier, W.R., Jr.; Médebielle, M. Nucleophilic Perfluoroalkylation of Aldehydes, Ketones, Imines, Disulfides, and Diselenides. *J. Org. Chem.* **2006**, *71*, 3564–3568. [CrossRef] [PubMed]

28. Pooput, C.; Medebielle, M.; Dolbier, W.R.J. A New and Efficient Method for the Synthesis of Trifluoromethylthio- and Selenoethers. *Org. Lett.* **2004**, *6*, 301–303. [CrossRef] [PubMed]

29. Médebielle, M.; Kato, K.; Dolbier, W.R., Jr. Fluorinated hydrazones. Part 1: Reductive coupling reactions of chlorodifluoroacetylated dialkylhydrazones using tetrakis(dimethylamino)ethylene (TDAE). *Tetrahedron Lett.* **2003**, *44*, 7871–7873. [CrossRef]

30. Montana, M.; Terme, T.; Vanelle, P. Original synthesis of α-chloroketones in azaheterocyclic series using TDAE approach. *Tetrahedron Lett.* **2006**, *47*, 6573–6576. [CrossRef]

31. Bergmann, E.; Hervey, J. Über das Auftreten von freien substituierten Methylenen bei chemischen Reaktionen. *Chem. Ber.* **1929**, *62*, 803–916. [CrossRef]

32. Stösser, R.; Thurne, J.-U.; Tomaschewski, U.; Ewert, P.; Eblik, P.; Sneide, W.; Hanke, T. EPR-Investigations on Radicals and Triplet States of Fluorene Derivatives. *Z. Naturforsh. A Phys. Sci.* **1982**, *37*, 1241–1246.

33. Goodman, C.C.; Roof, A.C.; Tillman, E.S.; Ludwig, B.; Chon, D.; Weigley, M.I. Synthesis and characterization of fluorene end-labeled polystyrene with atom transfer radical polymerization. *J. Polym. Sci. Pol. Chem.* **2005**, *43*, 2657–2665. [CrossRef]

34. Eisch, J.J.; Fregene, P.O. Vanadium(I) Chloride and Lithium Vanadium(I) Dihydride as Selective Epimetalating Reagents for π- and σ- Bonded Organic Substrates. *Eur. J. Org. Chem.* **2008**, *26*, 4482–4492. [CrossRef]

35. Ghera, E.; Sprinzak, Y. Reactions of active methylene compounds in pyridine soln. II. Aldol-type reactions of indene and fluorene. *J. Am. Chem. Soc.* **1960**, *82*, 4945–4952. [CrossRef]
36. Mladenova, G.; Singh, G.; Acton, A.; Chen, L.; Rinco, L.J.; Johnston, E.L.-R. Photochemical Pinacol Rearrangements of Unsymmetrical Diols. *J. Org. Chem.* **2004**, *69*, 2017–2023. [CrossRef] [PubMed]

37. Zhiqin, J.; Shuping, W.; Hansen, S. Studies on photooxidations. II. Electron transfer photooxidation of 9-benzylidenefluorene. *Hua Hsüeh Hsüeh Pao* **1988**, *46*, 294–297.

38. Allen, R.E.; Schumann, E.L.; Day, W.C.; Van Campen, M.G.J. Amidines of certain substituted triphenylethylenes. *J. Am. Chem. Soc.* **1958**, *80*, 591–598. [CrossRef]

**Sample Availability:** Samples of the compounds **4a–4g**; **4i–4p** and **5a–5c**; **5f–5k**; **6f** are available from the authors.

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