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Synlett 2024; 35(17): 2042-2048
DOI: 10.1055/a-2284-4984
letter
Special Section 14th EuCheMS Organic Division Young Investigator Workshop

Synthesis of Three-Dimensional Benzophenone Analogues Based on a [2.2]Paracyclophane Scaffold

Shiqi Wu
,
Laurent Micouin
,
Erica Benedetti∗

The authors gratefully thank the Agence Nationale de la Recherche (JCJC projet PhotoChiraPhane) (ANR-19-CE07-0001-01), the Centre National de la Recherche Scientifique (CNRS), Université Paris Cité (ANR-18-IDEX-0001), and the Ministère de l’Enseignement Supérieur et de la Recherche for financial support. The Chinese Scholarship Council is acknowledged for a grant to S.W.
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Abstract

Herein, we report the synthesis of functionalized three-dimensional benzophenone analogues derived from [2.2]paracyclophane (pCp). The potential use of these compounds as photocatalysts is disclosed. Benzophenone and its derivatives are well-known photoactive compounds that have been extensively employed over the years as catalysts to promote a variety of transformations activated by light. The development of differently substituted three-dimensional versions of such compounds may significantly expand the range of their applications in photocatalysis. Exploitation of the planar chirality of substituted paracyclophanes may also lead to significant innovations in different fields. [2.2]Paracyclophane-based benzophenone derivatives incorporating reactive ester or amide functions at their pseudo-gem position are successfully prepared in a selective manner. Examples of both racemic and enantiopure compounds are reported. As a proof of concept, the catalytic activities of the newly synthesized molecules are compared to that of benzophenone in a known photooxidation reaction.


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Key words

[2.2]paracyclophanes - planar chirality - benzophenone analogues - esters - primary amides
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Erica Benedetti(left) completed her doctoral studies at the University of Insubria, in collaboration with Sorbonne University, under the supervision of Prof. A. Penoni and Prof. L. Fensterbank, obtaining her Ph.D. in 2011. In 2012, she joined the research group of Prof. K. M. Brummond at the University of Pittsburgh as a postdoctoral fellow. After a postdoctoral stay at ESPCI ParisTech in the group of Prof. J. Cossy, in 2014, she became a CNRS researcher at Université Paris Cité. Her current research focuses on the synthesis and functionalization of planar chiral [2.2]paracyclophanes. In recognition of her achievements, she was awarded the CNRS Bronze Medal in 2022 and the Thieme Chemistry Journals Award in 2024. Laurent Micouin (center) studied at the Ecole Nationale Supérieure de Chimie de Paris, where he obtained an engineering diploma in 1990. He earned his Ph.D. in the laboratory of Prof. H.-P. Husson (Paris Descartes University) under the guidance of Prof. J.-C. Quirion in 1995. After a postdoctoral stay in Marburg (Germany) as a Humboldt Fellow under the direction of Prof. P. Knochel, he secured a permanent position at the CNRS in 1996. Since October 2005, he has been a Directeur de Recherche at Université Paris Cité. His primary research interests include methodological developments such as organoaluminum chemistry, asymmetric synthesis, and diversity-oriented synthesis. Shiqi Wu (right) completed his undergraduate studies at Dalian University of Technology and obtained his degree in chemical engineering in 2018. In the same year, he was awarded a CSC fellowship and joined the research group of Dr. E. Benedetti and Dr. L. Micouin at Université Paris Cité to pursue his doctoral studies. His research focused on the synthesis of luminescent [2.2]paracyclophane derivatives and the characterization of their photophysical properties. He successfully defended his Ph.D. in organic chemistry in July 2022.

[2.2]Paracyclophanes[1] (pCps) (see Scheme [1]) constitute an intriguing class of molecules with an uncommon sandwich-like aromatic structure[2] and unusual electronic behavior.[3] Due to these properties, pCps have been extensively used as building blocks in various research fields, including materials science,[4] fluorophore chemistry,[5] [6] organic synthesis, and catalysis.[7] In the latter domains, pCps have garnered considerable attention because they display planar chirality[8] as soon as a substituent is introduced onto their aromatic rings. [2.2]Paracyclophanes are configurationally stable up to 200 °C and highly resistant to the action of acids, bases, oxidants, and light irradiation. These characteristics make them ideal ligands and catalysts for asymmetric synthesis.[9] However, the preparation of polysubstituted pCps in a selective manner is often challenging due to functional group compatibilities and through-space stereoelectronic effects, which strongly influence the reactivity of the aromatic decks. Additionally, controlling the planar chirality of such complex molecules can be difficult to achieve.[10] The development of new synthetic procedures enabling straightforward access to functionalized planar chiral pCps remains a primary focus in modern cyclophane chemistry. In continuation of our ongoing research on selectively functionalizing pCps,[11] we have recently turned our attention to the preparation of novel compounds with potential for innovative applications.

In this report, we present a practical synthetic pathway to obtain pseudo-gem substituted benzophenone analogues derived from [2.2]paracyclophane. We also describe the synthesis of an enantiopure compound, demonstrating the ability to control the planar chirality of these new molecular entities. These molecules, which can be prepared on synthetically useful scales, may prove valuable in the future as electrochemical or photoactive stereocontrolling devices.

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Scheme 1 Synthesis of pCp-based benzophenone and initial attempts to access the targeted analogues

Benzophenone and its derivatives have been successfully used over the years as organophotocatalysts to promote a variety of transformations activated by light.[12] The synthesis of a pCp-based benzophenone (Scheme [1a]) was first reported in 1991 by Hopf and co-workers.[13] The preparation of other simple analogues of this molecule has also been described in the literature.[14] The potential use of these compounds to promote photoinduced transformations was anticipated in these seminal studies. In an effort to expand the potential range of applications of such molecules, we became interested in accessing more functionalized benzophenone analogues based on the pCp scaffold. Thus, we focused our attention on the preparation of useful synthetic intermediates by introducing different reactive substituents on the pCp core, particularly an ester or a primary amide function at the pseudo-gem position. Esterification of (±)-1 was initially attempted using a protocol previously employed to functionalize commercially available pCp. However, the reaction failed to deliver the desired product (Scheme [1b]).[15] Subsequently, direct bromination of (±)-1 was investigated, and compound (±)-2 was successfully isolated using the procedure described by Bräse and co-workers (Scheme [1c]).[16] It is noteworthy that in our experiments this reaction was not selective for the pseudo-gem position, as several by-products were detected by proton NMR of the crude reaction mixture. Palladium-catalyzed carbonylation reactions, which are known to occur with simpler benzene derivatives,[17] were attempted starting from (±)-2 but proved unsuccessful (Scheme [1c]).

We therefore modified the synthetic strategy to obtain the desired compounds (Scheme [2]). Ester (±)-5 was first prepared on a large scale starting from unsubstituted pCp according to a previously described procedure.[15] Subsequently, pseudo-gem formylation[18] of this intermediate was carried out using Rieche’s conditions[15b] to generate product (±)-6 in 62% yield. Grignard addition led to alcohol (±)-7a in 82% yield. It is worth noting that PhMgBr selectively reacted with the aldehyde function in this transformation. Finally, oxidation of (±)-7a with Dess–Martin periodinane (DMP) afforded compound (±)-3a in 75% overall yield.

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Scheme 2 Synthesis of product (±)-3a

A series of differently functionalized ketones derived from pCp and incorporating an ester moiety at their pseudo-gem position was prepared using this approach. Specifically, compounds (±)-3b–f were isolated in high overall yields by reacting intermediate (±)-6 with different Grignard reagents, followed by treatment of the resulting secondary alcohols with DMP (Scheme [3]).

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Scheme 3 Synthesis of products (±)-3b–f

The functionalized esters (±)-3a–f readily underwent hydrolysis with KOH in hot EtOH, yielding the corresponding acids (±)-8a–f in quantitative yields. Treatment of these acids with oxalyl chloride, followed by the addition of ammonia, allowed us to isolate the corresponding primary amides (±)-4a–f in good overall yields (Scheme [4]).

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Scheme 4 Synthesis of products (±)-4a–f

Products (±)-4a–f exhibited absorption profiles analogous to (±)-1 in dichloromethane, with maxima around 250 nm and 300 nm. In addition, all the compounds displayed a weak absorption band around 350 nm (see Figure [1a] for selected examples, and the Supporting Information for additional details). Cyclic voltammetry studies were also conducted. The voltammograms of (±)-4b and (±)-4d recorded in acetonitrile appeared similar to that of (±)-1 (Figure [1b]). However, lower reduction potentials were observed for the pCp-based analogues compared to the benzophenone derivative (see the Supporting Information for further details).

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Figure 1 Selected examples of (a) UV-Vis absorption and (b) cathodic reduction (IUPAC plotting convention) of pCp-based benzophenone analogues

All the compounds described up to now have been prepared in their racemic form. Optically active pCps 3d and 4d were also synthesized starting from enantiopure intermediate 6 (Scheme [5]). The racemic aldehyde precursor was resolved by chiral HPLC on a semipreparative scale (see the Supporting Information). When subjected to the synthetic pathway leading to the substituted pCp-based benzophenone analogues, aldehyde (+)-6 yielded compounds (+)-3d and (+)-4d, while its enantiomer (–)-6 readily afforded products (–)-3d and (–)-4d in good overall yields. The absolute configurations of all products could be determined by X-ray analysis of aldehyde (–)-6 (second eluted enantiomer, S p). Our findings are in agreement with recently reported data.[19]

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Scheme 5 Resolution of (±)-6 by HPLC on a chiral stationary phase

Table 1 Photoinduced Oxidation of Benzyl Alcohol via Singlet Oxygen Activation Promoted by Benzophenone and Its pCp-Based Analoguesa

Entry

Cat. (mol%)

Time

Conversionb

 1

  11 (10)

16 h

17%

 2

  –

16 h

 9%

 3

  11 (20)

16 h

21%

 4c

  11 (20)

16 h

18%

 5d

  11 (20)

16 h

 4%

 6

(±)-1 (20)

16 h

22%

 7

(±)-4a (20)

16 h

17%

 8

(±)-4c (20)

16 h

15%

 9

(±)-4d (20)

16 h

13%

10

   10 (20)

55 h

40%

11

(±)-1 (20)

55 h

42%

12

(±)-4c (20)

55 h

42%

13

(±)-4d (20)

55 h

20%

14

(±)-12 (20)

55 h

11%

a The reactions were conducted on a 0.2 mmol scale in 0.6 mL of solvent.

b Determined by 1H NMR of the crude reaction mixture.

c The reaction was conducted under an oxygen atmosphere.

d The reaction was conducted under an argon atmosphere.

We finally sought to demonstrate the potential utility of pCp-based analogues of benzophenone as photocatalysts in light-promoted transformations. As a proof of concept, we directed our focus to the photoinduced oxidation of benzyl alcohol (9) via singlet oxygen activation.[20] Initially, benzophenone (11) (10 mol%) was employed to promote the transformation. The reaction was conducted in deuterated dimethyl sulfoxide (DMSO-d 6), irradiating at 300–350 nm and 29 °C in ambient air. Under these conditions, benzaldehyde was formed with a 17% conversion after 16 hours (Table [1], entry 1). Notably, the reaction produced the desired product with only a 9% conversion in the absence of a photocatalyst (Table [1], entry 2). A slightly higher conversion was observed upon increasing the catalytic loading to 20 mol% (Table [1], entry 3). Unfortunately, this result was not improved on running the transformation under an oxygen atmosphere (Table [1], entry 4). The oxidation was almost completely prevented when performing the reaction under an argon atmosphere (Table [1], entry 5). Interestingly, the pCp-based derivative (±)-1 retained the photocatalytic activity of benzophenone in this transformation (Table [1], entry 6). The activity of di-substituted derivatives (±)-4a–f, containing a primary amide function, was also examined. Most of these compounds, exemplified by pCps (±)-4a, (±)-4c and (±)-4d (Table [1], entries 7–9), yielded the anticipated product with conversions comparable to that of (±)-1. Benzaldehyde (10) could be obtained in higher conversions (up to 42%) after 55 hours of irradiation, using photocatalysts (±)-1, (±)-4c, and (±)-4d (Table [1], entries 11–13). The pCp-based derivatives (±)-1 and (±)-4c performed similarly to compound 11 over the same reaction time (Table [1], entry 10), confirming that the introduction of reactive groups on the pCp core does not suppress the photosensitizing behavior of the molecules. Finally, we tested the reactivity of the pCp-based photoactive coumarin (±)-12, a compound known to promote light-induced desulfonylation reactions (Table [1], entry 14).[21] Although capable of activating singlet oxygen,[11c] [22] this molecule proved to be less efficient than (±)-1 in the photooxidation process, thus confirming that the benzophenone derivatives are more appropriate photocatalysts for this reaction.

In summary, we have developed a reliable synthetic pathway selectively leading to pseudo-gem-substituted benzophenone analogues derived from [2.2]paracyclophane.[23] [24] [25] [26] [27] [28] These synthesized compounds incorporate ester or primary amide reactive functions, providing starting points for further functionalization. Both racemic and enantiopure compounds were successfully prepared. Given the frequent use of benzophenone and its derivatives as promoters of light-induced transformations, we explored the potential application of pCp-based analogues as photocatalysts. Our results demonstrate that these three-dimensional molecules retain the photocatalytic activity of their parent compounds, as evidenced by their effectiveness in the photoinduced oxidation of benzyl alcohol.[29] Currently, our laboratory is investigating the use of pCp-benzophenone analogues as catalysts in other light-promoted transformations, including asymmetric reactions.


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Conflict of Interest

The authors declare no conflict of interest.

Acknowledgment

L.-M. Chamoreau, G. Gontard (Plateforme Diffraction X, IPCM, Sorbonne Université) and P. Gerardo (Plateforme de spectrométrie de masse, LCBPT, Université de Paris) are kindly acknowledged for their assistance with X-ray crystallography and mass analysis. We are grateful to N. Vanthuyine (iSm2, Aix-Marseille Université) for his assistance with chiral HPLC.

Supporting Information

    Supporting information for this article is available online at https://doi-org.accesdistant.sorbonne-universite.fr/10.1055/a-2284-4984.
  • Supporting Information

  • References and Notes

  • 1 Brown CJ, Farthing AC. Nature 1949; 164: 915
    CrossrefPubMedSearch in Google Scholar
  • 2 Hope H, Bernstein J, Trueblood KN. Acta Cryst. 1972; B28: 1733
    CrossrefSearch in Google Scholar
  • 3 Cram DJ, Allinger NL, Steinberg H. J. Am. Chem. Soc. 1954; 76: 6132
    CrossrefSearch in Google Scholar
  • 7 Hassan Z, Spuling E, Knoll DM, Bräse S. Angew. Chem. Int. Ed. 2020; 59: 2156
    CrossrefPubMedSearch in Google Scholar
  • 10 Felder S, Wu S, Brom J, Micouin L, Benedetti E. Chirality 2021; 33: 506
    CrossrefPubMedSearch in Google Scholar
  • 12 Amos SG. E, Garreau M, Buzzetti L, Waser J. Beilstein J. Org. Chem. 2020; 16: 1163
    CrossrefPubMedSearch in Google Scholar
  • 13 Hopf H, Laue T, Zander M. Angew. Chem., Int. Ed. Engl. 1991; 30: 432
    CrossrefSearch in Google Scholar
  • 16 Spuling E, Sharma N, Samuel ID. W, Zysman-Colman E, Bräse S. Chem. Commun. 2018; 54: 9278
    CrossrefPubMedSearch in Google Scholar
  • 17 Wan Y, Alterman M, Larhed M, Hallberg A. J. Comb. Chem. 2003; 5: 82
    CrossrefPubMedSearch in Google Scholar
  • 18 Rozenberg VI, Antonov DYu, Sergeeva EV, Vorontsov EV, Starikova ZA, Fedyanin IV, Schulz C, Hopf H. Eur. J. Org. Chem. 2003; 2056
    Crossref
  • 20 Nikitas NF, Tzaras DI, Triandafillidi I, Kokotos CG. Green Chem. 2020; 22: 471
    CrossrefSearch in Google Scholar
  • 21 Brom J, Maruani A, Turcaud S, Lajnef S, Peyrot F, Micouin L, Benedetti E. Org. Biomol. Chem. 2024; 22: 59
    CrossrefPubMedSearch in Google Scholar
  • 22 Wu S, Galan LA, Roux M, Riobe F, Le Guennic B, Guyot Y, Le Bahers T, Micouin L, Maury O, Benedetti E. Inorg. Chem. 2021; 60: 16194
    CrossrefPubMedSearch in Google Scholar
  • 23 Compound (±)-1 In a 50 mL flask, [2.2]paracyclophane (1 equiv., 2 g, 9.6 mmol) was dissolved in CH2Cl2 (20 mL) and cooled to –10 °C. A solution of benzoyl chloride (2 equiv., 2.7 g, 2.2 mL, 19.2 mmol) and AlCl3 (1.75 equiv., 2.24 g, 0.92 mL, 16.8 mmol) in CH2Cl2 (10 mL) was added and the reaction was stirred at –10 °C for 1 h. The mixture was then filtered and hydrolyzed with ice. The resulting aqueous solution was extracted with CH2Cl2 (3 × 15 mL). The combined organic layers were washed with aqueous NaHCO3 solution and brine, then dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude residue was purified by silica gel column chromatography (Cy/EtOAc = 30:1) to yield (±)-1 (2.4 g, 7.68 mmol, 80%) as a white solid. 1H NMR (600 MHz, CDCl3): δ = 7.72–7.68 (m, 2 H), 7.54 (td, J = 7.4, 1.4 Hz, 1 H), 7.41 (t, J = 7.7 Hz, 2 H), 6.75 (dd, J = 8.0, 1.3 Hz, 1 H), 6.72–6.68 (m, 2 H), 6.57 (t, J = 1.1 Hz, 2 H), 6.56 (d, J = 7.6 Hz, 1 H), 6.35 (d, J = 7.9 Hz, 1 H), 3.37–3.31 (m, 1 H), 3.28–3.22 (m, 1 H), 3.21–3.05 (m, 3 H), 3.04–2.92 (m, 2 H), 2.86 (ddd, J = 12.8, 10.4, 5.4 Hz, 1 H). 13C NMR (150 MHz, CDCl3): δ = 196.6 (C), 141.6 (C), 139.9 (C), 139.3 (C), 139.3 (C), 138.9 (C), 136.3 (C), 136.0 (CH), 135.7 (CH), 134.3 (CH), 132.7 (CH), 132.7 (CH), 132.4 (CH), 132.4 (CH), 131.1 (CH), 129.9 (2 CH), 128.2 (2 CH), 35.6 (CH2), 35.3 (CH2), 35.2 (CH2), 35.1 (CH2). The spectroscopic data are consistent with the literature data for this compound (see Ref. 13).
  • 24 Compound (±)-5 Anhydrous AlCl3 (1.9 equiv., 1.21 g, 9.09 mmol) was suspended in dry CH2Cl2 (50 mL) in a 100 mL round-bottomed flask. The mixture was cooled to –10 °C, and (COCl)2 (1.9 equiv., 1.18 g, 0.80 mL, 9.11 mmol) was added dropwise (pale yellow solution). The resulting suspension was stirred at –10 °C for 5 min, then [2.2]paracyclophane (1 equiv., 1 g, 4.8 mmol) was slowly added portionwise, turning the solution dark red. The reaction mixture was stirred at –10 °C for 30 min. About 50 g of ice was then added, turning the mixture yellow. The two immiscible layers were separated, and the aqueous phase was extracted with cold CH2Cl2 (–20 °C, 3 × 50 mL). The combined organic phases were kept at –20 °C, dried over MgSO4, and concentrated under reduced pressure in a cold bath. The resulting yellow solid (1 equiv., 1.43 g, 4.8 mmol) was suspended in dry chlorobenzene (40 mL). The solution was heated at reflux and stirred for 3 d. The mixture was then concentrated under reduced pressure. The resulting brown solid (1 equiv., 1.3 g, 4.8 mmol) was dissolved in a mixture of methanol (20 mL) and CH2Cl2 (6 mL). The solution was heated at reflux and stirred for 3 d. The mixture was then concentrated under vacuum. The crude product was purified by silica gel column chromatography (Cy/EtOAc = 30:1) to afford (±)-5 (823 mg, 3.09 mmol, 64%) as a white solid. 1H NMR (500 MHz, CDCl3): δ = 7.14 (d, J = 1.9 Hz, 1 H), 6.66 (dd, J = 7.7, 2.0 Hz, 1 H), 6.59–6.53 (m, 2 H), 6.52–6.43 (m, 3 H), 4.10 (ddd, J = 12.9, 9.8, 1.8 Hz, 1 H), 3.92 (s, 3 H), 3.26–2.94 (m, 6 H), 2.87 (ddd, J = 12.9, 10.1, 6.9 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 167.5 (C), 142.6 (C), 139.9 (C), 139.8 (C), 139.3 (C), 136.4 (CH), 136.1 (CH), 135.3 (CH), 133.1 (CH), 132.7 (CH), 132.2 (CH), 131.5 (CH), 130.7 (C), 51.7 (CH3), 36.1 (CH2), 35.2 (CH2), 35.1 (CH2), 34.9 (CH2). The synthesis of this compound was replicated several times. The spectroscopic data are consistent with the literature data for this compound (see Ref. 15).
  • 25 Compound (±)-6 A solution of (±)-5 (1 equiv., 1 g, 3.75 mmol) in anhydrous CH2Cl2 (30 mL) was cooled to –10 °C. TiCl4 (1 M solution in CH2Cl2, 3.5 equiv., 26 mL, 13.1 mmol) was added portionwise, followed by 1,1-dichlorodimethyl ether (3.5 equiv., 1.51 g, 1.19 mL, 13.1 mmol). The mixture was allowed to warm to room temperature and stirred under argon for 16 h. The reaction was then quenched by the addition of ice. The aqueous phase was extracted with CH2Cl2 (3 × 20 mL). The combined organic layers were washed with saturated aqueous NaHCO3 solution, water, and brine, then dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (Cy/EtOAc = 20:1) to afford (±)-6 (0.68 g, 2.31 mmol, 62%) as a white solid. 1H NMR (500 MHz, CDCl3): δ = 9.91 (s, 1 H), 7.07 (t, J = 1.8 Hz, 2 H), 6.72–6.67 (m, 2 H), 6.65–6.60 (m, 2 H), 4.29–4.05 (m, 2 H), 3.81 (s, 3 H), 3.21–3.05 (m, 5 H), 3.05–2.93 (m, 1 H). 13C NMR (125 MHz, CDCl3): δ = 190.6 (CH), 167.0 (C), 143.5 (C), 142.1 (C), 140.1 (C), 139.7 (C), 138.2 (CH), 136.6 (C), 136.2 (CH), 136.0 (CH), 135.7 (CH), 134.5 (CH), 133.8 (CH), 130.8 (C), 51.9 (CH3), 35.0 (CH2), 34.8 (CH2), 34.6 (CH2), 31.2 (CH2). The spectroscopic data are consistent with the literature data for this compound (see Ref. 18).
  • 26 Grignard Reaction for the Synthesis of Intermediate (±)-7a; Representative Procedure A Compound (±)-6 (1 equiv., 500 mg, 1.7 mmol) was dissolved in dry THF (10 mL) under an argon atmosphere. PhMgBr (1.2 equiv., 1 M in THF, 2.0 mL, 2.0 mmol) was added dropwise, and the resulting solution was stirred for 1 h at room temperature. The reaction was then quenched by the addition of saturated aqueous NH4Cl solution. THF was removed under vacuum, and the resulting mixture was extracted with EtOAc (3 × 15 mL). The combined organic layers were washed with brine, dried over MgSO4, and concentrated under reduced pressure. The crude residue was purified by silica gel column chromatography (Cy/EtOAc = 25:1) to yield product (±)-7a (520 mg, 1.4 mmol, 82%) as a white solid. IR (neat): 3498, 2949, 1711, 1594, 1492, 1436, 1274, 1199, 1096, 1077, 1033, 919, 872, 793, 764, 730 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.21–7.16 (m, 4 H), 7.15–7.08 (m, 3 H), 6.98 (s, 1 H), 6.72 (d, J = 7.7 Hz, 1 H), 6.62 (d, J = 7.7 Hz, 1 H), 6.50 (d, J = 7.2 Hz, 1 H), 6.46 (d, J = 7.6 Hz, 1 H), 5.65 (d, J = 3.7 Hz, 1 H), 4.05 (ddd, J = 13.7, 10.0, 3.7 Hz, 1 H), 3.98 (d, J = 1.2 Hz, 3 H), 3.39 (dd, J = 3.8, 1.2 Hz, 1 H), 3.32 (ddd, J = 13.8, 9.9, 4.3 Hz, 1 H), 3.21–3.03 (m, 4 H), 2.89 (ddd, J = 13.8, 10.5, 3.7 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 169.6 (C), 143.5 (C), 143.3 (C), 141.8 (C), 139.9 (C), 139.8 (C), 137.1 (CH), 136.1 (CH), 135.4 (C), 134.9 (CH), 134.4 (CH), 131.9 (CH), 129.3 (C), 128.3 (2 CH), 127.7 (CH), 127.2 (CH), 127.0 (2 CH), 72.6 (CH), 52.4 (CH3), 35.0 (CH2), 34.9 (CH2), 34.1 (CH2), 32.3 (CH2). HRMS (ESI): m/z [M + Na]+ calcd for C25H24O3Na: 395.1618; found: 395.1618.
  • 27 Oxidation Reaction for the Synthesis of Compound (±)-3a; Representative Procedure B In a round-bottomed flask under an argon atmosphere, compound (±)-7a (1 equiv., 420 mg, 1.13 mmol) was dissolved in CH2Cl2 (9 mL). Dess–Martin periodinane (DMP, 1.25 equiv., 599 mg, 1.41 mmol) was then added to the reaction mixture. The resulting solution was stirred overnight at room temperature. The reaction was quenched by the addition of saturated aqueous NaHCO3 solution. The immiscible phases were separated, and the aqueous layer was extracted with CH2Cl2 (×2). The combined organic phases were washed with water and brine, dried over MgSO4, and concentrated under reduced pressure. The crude residue was purified by silica gel column chromatography (Cy/EtOAc = 35:1) to yield product (±)-3a (386 mg, 1.04 mmol, 92%) as a white solid. IR (neat): 1716, 1657, 1596, 1556, 1435, 1275, 1196, 1076, 953, 861, 800, 764, 750, 720 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.67–7.64 (m, 2 H), 7.53–7.49 (m, 1 H), 7.42–7.37 (m, 2 H), 7.19 (d, J = 2.1 Hz, 1 H), 6.89 (d, J = 1.9 Hz, 1 H), 6.72 (ddd, J = 7.8, 5.6, 2.0 Hz, 2 H), 6.66 (d, J = 7.9 Hz, 1 H), 6.61 (d, J = 7.8 Hz, 1 H), 4.14 (t, J = 10.0 Hz, 1 H), 3.96 (s, 3 H), 3.33–3.23 (m, 1 H), 3.19–3.05 (m, 4 H), 2.94–2.86 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ = 196.0 (C), 167.2 (C), 142.5 (C), 141.9 (C), 139.5 (C), 139.3 (C), 139.2 (C), 137.0 (C), 136.2 (CH), 136.1 (CH), 135.9 (CH), 135.1 (CH), 134.5 (CH), 133.6 (CH), 132.1 (CH), 129.8 (2 CH), 129.6 (C), 128.1 (2 CH), 51.9 (CH3), 35.7 (CH2), 34.8 (CH2), 34.8 (CH2), 34.7 (CH2). HRMS (ESI): m/z [M + H]+ calcd for C25H23O3: 371.1642; found: 371.1641.
  • 28 Synthesis of Primary Amide (±)-4a; Representative Procedure C To a solution of compound (±)-3a (1 equiv., 200 mg, 0.54 mmol) in EtOH (5.5 mL) was added a solution of KOH (10 equiv., 2 M in H2O, 2.7 mL, 5.4 mmol). The resulting mixture was heated at reflux and stirred for 5 h. The reaction was then cooled to room temperature and acidified to pH 5 with an aqueous HCl solution (2 M). The resulting mixture was extracted with CH2Cl2, dried over MgSO4, and concentrated under reduced pressure to afford the carboxylic acid (±)-8a (190 mg, 0.533 mmol, 99%) as a white solid. To a suspension of this compound (1 equiv.) in CH2Cl2 (5.5 mL), oxalyl chloride (1.2 equiv., 81 mg, 55 μL, 0.64 mmol) was added, followed by a few drops of DMF (10 mol%, 5 μL, 0.05 mmol). The solution was stirred overnight at room temperature. The solvent was then removed under reduced pressure to afford the desired acyl chloride derivative (198 mg, 0.528 mmol, quant.) as a yellow solid. This product (1 equiv.) was dissolved in dry acetone (4.5 mL). NH4OH (32 equiv., 2.4 mL, 16.9 mmol) was added at 5 °C, and the solution was stirred for 1 h. Water was then added, and the acetone was evaporated under reduced pressure. The resulting aqueous solution was extracted with EtOAc (3 × 15 mL). The combined organic layers were washed with saturated aqueous Na2CO3 solution and water, dried over Na2SO4, and concentrated in vacuo. The crude residue was purified by silica gel column chromatography (Cy/EtOAc = 2:1) to afford (±)-4a (160 mg, 0.45 mmol, 85%) as a white solid. IR (neat): 3005, 1657, 1596, 1555, 1447, 1371, 1322, 1276, 1075, 839, 802, 742, 720 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.66 (d, J = 7.8 Hz, 2 H), 7.50 (t, J = 7.3 Hz, 1 H), 7.39 (t, J = 7.7 Hz, 2 H), 6.99 (s, 1 H), 6.86 (s, 1 H), 6.77 (dd, J = 7.7, 1.4 Hz, 1 H), 6.69 (d, J = 7.9 Hz, 2 H), 6.63 (d, J = 7.7 Hz, 1 H), 5.62 (s, 2 H), 4.01–3.83 (m, 1 H), 3.37–3.25 (m, 1 H), 3.23–2.98 (m, 4 H), 2.97–2.86 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ = 196.1 (C), 170.3 (C), 142.2 (C), 139.9 (C), 139.7 (C), 139.5 (C), 139.1 (C), 136.4 (C), 136.3 (CH), 136.1 (CH), 135.2 (CH), 135.2 (CH), 134.1 (CH), 133.2 (C), 132.0 (CH), 131.7 (CH), 129.9 (2 CH), 128.1 (2 CH), 36.0 (CH2), 35.2 (CH2), 34.8 (CH2), 34.7 (CH2). HRMS (ESI): m/z [M + H]+ calcd for C24H22O2N: 356.1645; found: 356.1644.
  • 29 Photooxidation of Benzylic Alcohol in the Presence of Catalyst (±)-1; Representative Procedure D In a glass vial, (±)-1 (0.2 equiv., 14 mg, 0.046 mmol) was dissolved in DMSO-d 6 (0.6 mL). Benzyl alcohol (9) (1 equiv., 22 mg, 21 μL, 0.2 mmol) was added to the mixture. The vial was then placed in a Rayonet photoreactor, and the reaction was irradiated at 300–350 nm under air for 55 h (Temp = 29 °C). Water (10 mL) and CH2Cl2 (10 mL) were then added. The phases were separated, and the aqueous layer was extracted with CH2Cl2 (3 × 10 mL). The combined organic phases were washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The conversion (unreacted starting material vs desired product) was determined by 1H NMR analysis of the crude reaction mixture.

Corresponding Author

Erica Benedetti
Université Paris Cité, CNRS, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques
75006 Paris
France   

Publication History

Received: 16 February 2024

Accepted after revision: 10 March 2024

Accepted Manuscript online:
10 March 2024

Article published online:
26 March 2024

© 2024. Thieme. All rights reserved

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  • References and Notes

  • 1 Brown CJ, Farthing AC. Nature 1949; 164: 915
    CrossrefPubMedSearch in Google Scholar
  • 2 Hope H, Bernstein J, Trueblood KN. Acta Cryst. 1972; B28: 1733
    CrossrefSearch in Google Scholar
  • 3 Cram DJ, Allinger NL, Steinberg H. J. Am. Chem. Soc. 1954; 76: 6132
    CrossrefSearch in Google Scholar
  • 7 Hassan Z, Spuling E, Knoll DM, Bräse S. Angew. Chem. Int. Ed. 2020; 59: 2156
    CrossrefPubMedSearch in Google Scholar
  • 10 Felder S, Wu S, Brom J, Micouin L, Benedetti E. Chirality 2021; 33: 506
    CrossrefPubMedSearch in Google Scholar
  • 12 Amos SG. E, Garreau M, Buzzetti L, Waser J. Beilstein J. Org. Chem. 2020; 16: 1163
    CrossrefPubMedSearch in Google Scholar
  • 13 Hopf H, Laue T, Zander M. Angew. Chem., Int. Ed. Engl. 1991; 30: 432
    CrossrefSearch in Google Scholar
  • 16 Spuling E, Sharma N, Samuel ID. W, Zysman-Colman E, Bräse S. Chem. Commun. 2018; 54: 9278
    CrossrefPubMedSearch in Google Scholar
  • 17 Wan Y, Alterman M, Larhed M, Hallberg A. J. Comb. Chem. 2003; 5: 82
    CrossrefPubMedSearch in Google Scholar
  • 18 Rozenberg VI, Antonov DYu, Sergeeva EV, Vorontsov EV, Starikova ZA, Fedyanin IV, Schulz C, Hopf H. Eur. J. Org. Chem. 2003; 2056
    Crossref
  • 20 Nikitas NF, Tzaras DI, Triandafillidi I, Kokotos CG. Green Chem. 2020; 22: 471
    CrossrefSearch in Google Scholar
  • 21 Brom J, Maruani A, Turcaud S, Lajnef S, Peyrot F, Micouin L, Benedetti E. Org. Biomol. Chem. 2024; 22: 59
    CrossrefPubMedSearch in Google Scholar
  • 22 Wu S, Galan LA, Roux M, Riobe F, Le Guennic B, Guyot Y, Le Bahers T, Micouin L, Maury O, Benedetti E. Inorg. Chem. 2021; 60: 16194
    CrossrefPubMedSearch in Google Scholar
  • 23 Compound (±)-1 In a 50 mL flask, [2.2]paracyclophane (1 equiv., 2 g, 9.6 mmol) was dissolved in CH2Cl2 (20 mL) and cooled to –10 °C. A solution of benzoyl chloride (2 equiv., 2.7 g, 2.2 mL, 19.2 mmol) and AlCl3 (1.75 equiv., 2.24 g, 0.92 mL, 16.8 mmol) in CH2Cl2 (10 mL) was added and the reaction was stirred at –10 °C for 1 h. The mixture was then filtered and hydrolyzed with ice. The resulting aqueous solution was extracted with CH2Cl2 (3 × 15 mL). The combined organic layers were washed with aqueous NaHCO3 solution and brine, then dried over Na2SO4. The solvent was evaporated under reduced pressure and the crude residue was purified by silica gel column chromatography (Cy/EtOAc = 30:1) to yield (±)-1 (2.4 g, 7.68 mmol, 80%) as a white solid. 1H NMR (600 MHz, CDCl3): δ = 7.72–7.68 (m, 2 H), 7.54 (td, J = 7.4, 1.4 Hz, 1 H), 7.41 (t, J = 7.7 Hz, 2 H), 6.75 (dd, J = 8.0, 1.3 Hz, 1 H), 6.72–6.68 (m, 2 H), 6.57 (t, J = 1.1 Hz, 2 H), 6.56 (d, J = 7.6 Hz, 1 H), 6.35 (d, J = 7.9 Hz, 1 H), 3.37–3.31 (m, 1 H), 3.28–3.22 (m, 1 H), 3.21–3.05 (m, 3 H), 3.04–2.92 (m, 2 H), 2.86 (ddd, J = 12.8, 10.4, 5.4 Hz, 1 H). 13C NMR (150 MHz, CDCl3): δ = 196.6 (C), 141.6 (C), 139.9 (C), 139.3 (C), 139.3 (C), 138.9 (C), 136.3 (C), 136.0 (CH), 135.7 (CH), 134.3 (CH), 132.7 (CH), 132.7 (CH), 132.4 (CH), 132.4 (CH), 131.1 (CH), 129.9 (2 CH), 128.2 (2 CH), 35.6 (CH2), 35.3 (CH2), 35.2 (CH2), 35.1 (CH2). The spectroscopic data are consistent with the literature data for this compound (see Ref. 13).
  • 24 Compound (±)-5 Anhydrous AlCl3 (1.9 equiv., 1.21 g, 9.09 mmol) was suspended in dry CH2Cl2 (50 mL) in a 100 mL round-bottomed flask. The mixture was cooled to –10 °C, and (COCl)2 (1.9 equiv., 1.18 g, 0.80 mL, 9.11 mmol) was added dropwise (pale yellow solution). The resulting suspension was stirred at –10 °C for 5 min, then [2.2]paracyclophane (1 equiv., 1 g, 4.8 mmol) was slowly added portionwise, turning the solution dark red. The reaction mixture was stirred at –10 °C for 30 min. About 50 g of ice was then added, turning the mixture yellow. The two immiscible layers were separated, and the aqueous phase was extracted with cold CH2Cl2 (–20 °C, 3 × 50 mL). The combined organic phases were kept at –20 °C, dried over MgSO4, and concentrated under reduced pressure in a cold bath. The resulting yellow solid (1 equiv., 1.43 g, 4.8 mmol) was suspended in dry chlorobenzene (40 mL). The solution was heated at reflux and stirred for 3 d. The mixture was then concentrated under reduced pressure. The resulting brown solid (1 equiv., 1.3 g, 4.8 mmol) was dissolved in a mixture of methanol (20 mL) and CH2Cl2 (6 mL). The solution was heated at reflux and stirred for 3 d. The mixture was then concentrated under vacuum. The crude product was purified by silica gel column chromatography (Cy/EtOAc = 30:1) to afford (±)-5 (823 mg, 3.09 mmol, 64%) as a white solid. 1H NMR (500 MHz, CDCl3): δ = 7.14 (d, J = 1.9 Hz, 1 H), 6.66 (dd, J = 7.7, 2.0 Hz, 1 H), 6.59–6.53 (m, 2 H), 6.52–6.43 (m, 3 H), 4.10 (ddd, J = 12.9, 9.8, 1.8 Hz, 1 H), 3.92 (s, 3 H), 3.26–2.94 (m, 6 H), 2.87 (ddd, J = 12.9, 10.1, 6.9 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 167.5 (C), 142.6 (C), 139.9 (C), 139.8 (C), 139.3 (C), 136.4 (CH), 136.1 (CH), 135.3 (CH), 133.1 (CH), 132.7 (CH), 132.2 (CH), 131.5 (CH), 130.7 (C), 51.7 (CH3), 36.1 (CH2), 35.2 (CH2), 35.1 (CH2), 34.9 (CH2). The synthesis of this compound was replicated several times. The spectroscopic data are consistent with the literature data for this compound (see Ref. 15).
  • 25 Compound (±)-6 A solution of (±)-5 (1 equiv., 1 g, 3.75 mmol) in anhydrous CH2Cl2 (30 mL) was cooled to –10 °C. TiCl4 (1 M solution in CH2Cl2, 3.5 equiv., 26 mL, 13.1 mmol) was added portionwise, followed by 1,1-dichlorodimethyl ether (3.5 equiv., 1.51 g, 1.19 mL, 13.1 mmol). The mixture was allowed to warm to room temperature and stirred under argon for 16 h. The reaction was then quenched by the addition of ice. The aqueous phase was extracted with CH2Cl2 (3 × 20 mL). The combined organic layers were washed with saturated aqueous NaHCO3 solution, water, and brine, then dried over MgSO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (Cy/EtOAc = 20:1) to afford (±)-6 (0.68 g, 2.31 mmol, 62%) as a white solid. 1H NMR (500 MHz, CDCl3): δ = 9.91 (s, 1 H), 7.07 (t, J = 1.8 Hz, 2 H), 6.72–6.67 (m, 2 H), 6.65–6.60 (m, 2 H), 4.29–4.05 (m, 2 H), 3.81 (s, 3 H), 3.21–3.05 (m, 5 H), 3.05–2.93 (m, 1 H). 13C NMR (125 MHz, CDCl3): δ = 190.6 (CH), 167.0 (C), 143.5 (C), 142.1 (C), 140.1 (C), 139.7 (C), 138.2 (CH), 136.6 (C), 136.2 (CH), 136.0 (CH), 135.7 (CH), 134.5 (CH), 133.8 (CH), 130.8 (C), 51.9 (CH3), 35.0 (CH2), 34.8 (CH2), 34.6 (CH2), 31.2 (CH2). The spectroscopic data are consistent with the literature data for this compound (see Ref. 18).
  • 26 Grignard Reaction for the Synthesis of Intermediate (±)-7a; Representative Procedure A Compound (±)-6 (1 equiv., 500 mg, 1.7 mmol) was dissolved in dry THF (10 mL) under an argon atmosphere. PhMgBr (1.2 equiv., 1 M in THF, 2.0 mL, 2.0 mmol) was added dropwise, and the resulting solution was stirred for 1 h at room temperature. The reaction was then quenched by the addition of saturated aqueous NH4Cl solution. THF was removed under vacuum, and the resulting mixture was extracted with EtOAc (3 × 15 mL). The combined organic layers were washed with brine, dried over MgSO4, and concentrated under reduced pressure. The crude residue was purified by silica gel column chromatography (Cy/EtOAc = 25:1) to yield product (±)-7a (520 mg, 1.4 mmol, 82%) as a white solid. IR (neat): 3498, 2949, 1711, 1594, 1492, 1436, 1274, 1199, 1096, 1077, 1033, 919, 872, 793, 764, 730 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.21–7.16 (m, 4 H), 7.15–7.08 (m, 3 H), 6.98 (s, 1 H), 6.72 (d, J = 7.7 Hz, 1 H), 6.62 (d, J = 7.7 Hz, 1 H), 6.50 (d, J = 7.2 Hz, 1 H), 6.46 (d, J = 7.6 Hz, 1 H), 5.65 (d, J = 3.7 Hz, 1 H), 4.05 (ddd, J = 13.7, 10.0, 3.7 Hz, 1 H), 3.98 (d, J = 1.2 Hz, 3 H), 3.39 (dd, J = 3.8, 1.2 Hz, 1 H), 3.32 (ddd, J = 13.8, 9.9, 4.3 Hz, 1 H), 3.21–3.03 (m, 4 H), 2.89 (ddd, J = 13.8, 10.5, 3.7 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 169.6 (C), 143.5 (C), 143.3 (C), 141.8 (C), 139.9 (C), 139.8 (C), 137.1 (CH), 136.1 (CH), 135.4 (C), 134.9 (CH), 134.4 (CH), 131.9 (CH), 129.3 (C), 128.3 (2 CH), 127.7 (CH), 127.2 (CH), 127.0 (2 CH), 72.6 (CH), 52.4 (CH3), 35.0 (CH2), 34.9 (CH2), 34.1 (CH2), 32.3 (CH2). HRMS (ESI): m/z [M + Na]+ calcd for C25H24O3Na: 395.1618; found: 395.1618.
  • 27 Oxidation Reaction for the Synthesis of Compound (±)-3a; Representative Procedure B In a round-bottomed flask under an argon atmosphere, compound (±)-7a (1 equiv., 420 mg, 1.13 mmol) was dissolved in CH2Cl2 (9 mL). Dess–Martin periodinane (DMP, 1.25 equiv., 599 mg, 1.41 mmol) was then added to the reaction mixture. The resulting solution was stirred overnight at room temperature. The reaction was quenched by the addition of saturated aqueous NaHCO3 solution. The immiscible phases were separated, and the aqueous layer was extracted with CH2Cl2 (×2). The combined organic phases were washed with water and brine, dried over MgSO4, and concentrated under reduced pressure. The crude residue was purified by silica gel column chromatography (Cy/EtOAc = 35:1) to yield product (±)-3a (386 mg, 1.04 mmol, 92%) as a white solid. IR (neat): 1716, 1657, 1596, 1556, 1435, 1275, 1196, 1076, 953, 861, 800, 764, 750, 720 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.67–7.64 (m, 2 H), 7.53–7.49 (m, 1 H), 7.42–7.37 (m, 2 H), 7.19 (d, J = 2.1 Hz, 1 H), 6.89 (d, J = 1.9 Hz, 1 H), 6.72 (ddd, J = 7.8, 5.6, 2.0 Hz, 2 H), 6.66 (d, J = 7.9 Hz, 1 H), 6.61 (d, J = 7.8 Hz, 1 H), 4.14 (t, J = 10.0 Hz, 1 H), 3.96 (s, 3 H), 3.33–3.23 (m, 1 H), 3.19–3.05 (m, 4 H), 2.94–2.86 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ = 196.0 (C), 167.2 (C), 142.5 (C), 141.9 (C), 139.5 (C), 139.3 (C), 139.2 (C), 137.0 (C), 136.2 (CH), 136.1 (CH), 135.9 (CH), 135.1 (CH), 134.5 (CH), 133.6 (CH), 132.1 (CH), 129.8 (2 CH), 129.6 (C), 128.1 (2 CH), 51.9 (CH3), 35.7 (CH2), 34.8 (CH2), 34.8 (CH2), 34.7 (CH2). HRMS (ESI): m/z [M + H]+ calcd for C25H23O3: 371.1642; found: 371.1641.
  • 28 Synthesis of Primary Amide (±)-4a; Representative Procedure C To a solution of compound (±)-3a (1 equiv., 200 mg, 0.54 mmol) in EtOH (5.5 mL) was added a solution of KOH (10 equiv., 2 M in H2O, 2.7 mL, 5.4 mmol). The resulting mixture was heated at reflux and stirred for 5 h. The reaction was then cooled to room temperature and acidified to pH 5 with an aqueous HCl solution (2 M). The resulting mixture was extracted with CH2Cl2, dried over MgSO4, and concentrated under reduced pressure to afford the carboxylic acid (±)-8a (190 mg, 0.533 mmol, 99%) as a white solid. To a suspension of this compound (1 equiv.) in CH2Cl2 (5.5 mL), oxalyl chloride (1.2 equiv., 81 mg, 55 μL, 0.64 mmol) was added, followed by a few drops of DMF (10 mol%, 5 μL, 0.05 mmol). The solution was stirred overnight at room temperature. The solvent was then removed under reduced pressure to afford the desired acyl chloride derivative (198 mg, 0.528 mmol, quant.) as a yellow solid. This product (1 equiv.) was dissolved in dry acetone (4.5 mL). NH4OH (32 equiv., 2.4 mL, 16.9 mmol) was added at 5 °C, and the solution was stirred for 1 h. Water was then added, and the acetone was evaporated under reduced pressure. The resulting aqueous solution was extracted with EtOAc (3 × 15 mL). The combined organic layers were washed with saturated aqueous Na2CO3 solution and water, dried over Na2SO4, and concentrated in vacuo. The crude residue was purified by silica gel column chromatography (Cy/EtOAc = 2:1) to afford (±)-4a (160 mg, 0.45 mmol, 85%) as a white solid. IR (neat): 3005, 1657, 1596, 1555, 1447, 1371, 1322, 1276, 1075, 839, 802, 742, 720 cm–1. 1H NMR (500 MHz, CDCl3): δ = 7.66 (d, J = 7.8 Hz, 2 H), 7.50 (t, J = 7.3 Hz, 1 H), 7.39 (t, J = 7.7 Hz, 2 H), 6.99 (s, 1 H), 6.86 (s, 1 H), 6.77 (dd, J = 7.7, 1.4 Hz, 1 H), 6.69 (d, J = 7.9 Hz, 2 H), 6.63 (d, J = 7.7 Hz, 1 H), 5.62 (s, 2 H), 4.01–3.83 (m, 1 H), 3.37–3.25 (m, 1 H), 3.23–2.98 (m, 4 H), 2.97–2.86 (m, 2 H). 13C NMR (125 MHz, CDCl3): δ = 196.1 (C), 170.3 (C), 142.2 (C), 139.9 (C), 139.7 (C), 139.5 (C), 139.1 (C), 136.4 (C), 136.3 (CH), 136.1 (CH), 135.2 (CH), 135.2 (CH), 134.1 (CH), 133.2 (C), 132.0 (CH), 131.7 (CH), 129.9 (2 CH), 128.1 (2 CH), 36.0 (CH2), 35.2 (CH2), 34.8 (CH2), 34.7 (CH2). HRMS (ESI): m/z [M + H]+ calcd for C24H22O2N: 356.1645; found: 356.1644.
  • 29 Photooxidation of Benzylic Alcohol in the Presence of Catalyst (±)-1; Representative Procedure D In a glass vial, (±)-1 (0.2 equiv., 14 mg, 0.046 mmol) was dissolved in DMSO-d 6 (0.6 mL). Benzyl alcohol (9) (1 equiv., 22 mg, 21 μL, 0.2 mmol) was added to the mixture. The vial was then placed in a Rayonet photoreactor, and the reaction was irradiated at 300–350 nm under air for 55 h (Temp = 29 °C). Water (10 mL) and CH2Cl2 (10 mL) were then added. The phases were separated, and the aqueous layer was extracted with CH2Cl2 (3 × 10 mL). The combined organic phases were washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The conversion (unreacted starting material vs desired product) was determined by 1H NMR analysis of the crude reaction mixture.

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Erica Benedetti(left) completed her doctoral studies at the University of Insubria, in collaboration with Sorbonne University, under the supervision of Prof. A. Penoni and Prof. L. Fensterbank, obtaining her Ph.D. in 2011. In 2012, she joined the research group of Prof. K. M. Brummond at the University of Pittsburgh as a postdoctoral fellow. After a postdoctoral stay at ESPCI ParisTech in the group of Prof. J. Cossy, in 2014, she became a CNRS researcher at Université Paris Cité. Her current research focuses on the synthesis and functionalization of planar chiral [2.2]paracyclophanes. In recognition of her achievements, she was awarded the CNRS Bronze Medal in 2022 and the Thieme Chemistry Journals Award in 2024. Laurent Micouin (center) studied at the Ecole Nationale Supérieure de Chimie de Paris, where he obtained an engineering diploma in 1990. He earned his Ph.D. in the laboratory of Prof. H.-P. Husson (Paris Descartes University) under the guidance of Prof. J.-C. Quirion in 1995. After a postdoctoral stay in Marburg (Germany) as a Humboldt Fellow under the direction of Prof. P. Knochel, he secured a permanent position at the CNRS in 1996. Since October 2005, he has been a Directeur de Recherche at Université Paris Cité. His primary research interests include methodological developments such as organoaluminum chemistry, asymmetric synthesis, and diversity-oriented synthesis. Shiqi Wu (right) completed his undergraduate studies at Dalian University of Technology and obtained his degree in chemical engineering in 2018. In the same year, he was awarded a CSC fellowship and joined the research group of Dr. E. Benedetti and Dr. L. Micouin at Université Paris Cité to pursue his doctoral studies. His research focused on the synthesis of luminescent [2.2]paracyclophane derivatives and the characterization of their photophysical properties. He successfully defended his Ph.D. in organic chemistry in July 2022.
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Scheme 1 Synthesis of pCp-based benzophenone and initial attempts to access the targeted analogues
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Scheme 2 Synthesis of product (±)-3a
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Scheme 3 Synthesis of products (±)-3b–f
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Scheme 4 Synthesis of products (±)-4a–f
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Figure 1 Selected examples of (a) UV-Vis absorption and (b) cathodic reduction (IUPAC plotting convention) of pCp-based benzophenone analogues
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Scheme 5 Resolution of (±)-6 by HPLC on a chiral stationary phase