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Article

Synthesis of Fused Cyclic Aryl Amino Carbon Carbene Salt Precursors ([f-CArACH]+) Incorporating an Auxiliary Arene and Isolation of a Cu(I) Complex

by
Polidoros Chrisovalantis. Ioannou
,
Nikolaos Tsoureas
* and
Sevasti-Panagiota Kotsaki
Inorganic Chemistry Laboratory, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupoli Zografou, 157 72 Athens, Greece
*
Author to whom correspondence should be addressed.
Organics 2025, 6(4), 51; https://doi.org/10.3390/org6040051
Submission received: 23 September 2025 / Revised: 27 October 2025 / Accepted: 31 October 2025 / Published: 10 November 2025
(This article belongs to the Special Issue Chemistry of Heterocyclic Compounds)
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Abstract

The synthesis of a small library of fused Cyclic Aryl Amino Carbon (f-CArAC) carbene precursors in the form of 1,1,2,4-tetraaryl-1H-isoindol-2-ium triflate (6), (7-R) (R = tBu, CF3) or 3,3-dimethyl-2,8-bis-arene-substituted-3,4-dihydro-isoquinolin-2-ium hydrogen-dichloride (8) and 2,4,8-tri(substituted)-isoquinolin-2-ium tosylate salts (12) has been achieved. All of them feature an arene incorporated on the annulated benzene ring of the corresponding heterocycle, introduced at the early stages of their synthesis via the Suzuki cross-coupling reaction between 2,6-dibromo-benzaldehyde and the desired aryl boronic acid. The terphenyl-2′carbaldehyde by-products of this Suzuki reaction are useful starting points for the preparation of two new iminium iodide salts (10-R) (R = H, CF3) as potential precursors to access ACyclic Amino Carbon (ACAC) carbenes. Compounds (6) and (7-tBu) react readily with hydroxide either in THF or in a biphasic Et2O/aqueous OH− solution to produce the substituted isoindolinols (13) and (14), respectively. The thermal dehydration of the former generates the corresponding f-CArAC carbene in situ, which is trapped by Cu(I)Cl furnishing, a rare example of a two-coordinate Cu(I) complex (15) supported by this new ligand scaffold.

1. Introduction

Nitrogen containing heterocycles are ubiquitous compounds with a multitude of applications in polymers [1,2], pharmaceuticals [3,4], dyes [4,5,6], organocatalysis [7,8,9,10,11] and more recently photochemistry [12,13,14,15], to name a few. From the standpoint of organometallic chemistry, they feature as important moieties in various ligands, out of which N-heterocyclic-ylidenes (NHCs) [16,17], incorporating at least another heteroatom in their scaffold [18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60], are an important class with some representative examples shown in Figure 1(1A). Τheir diverse substitution patterns and architectural motifs enable the manipulation of their intrinsic electronic properties (e.g., HOMO-LUMO gap) [17,61], as well as their donating (σ-donation/π-acceptance) [41,50,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77] and steric parameters [62,77,78,79,80] especially when coordinated to metals, usually, as L type ligands [31,77,81,82,83,84,85,86,87,88].
Substituting the N-R1 group in the case of saturated imidazolin-2-ylidenes (i.e., second scaffold from left at the top of Figure 1(1A)) by a CRR’ moiety gives rise to Cyclic Alkyl Amino Carbenes (CAACs) (Figure 1(1B))—an important subclass of isolable singlet state carbenes [61,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103] with a reduced HOMO-LUMO energy gap. This increases their σ-donating properties, but crucially also renders the orthogonal empty p-orbital of the carbene carbon (i.e., the LUMO) energetically accessible for π-backdonation. As a result, they can promote reactivity reminiscent of transition metals [104] and allow the stabilisation and isolation of low coordinate compounds of both transition metals [94,105,106,107,108,109,110,111,112,113,114,115] and main group elements [94,97,116,117,118,119,120,121,122,123,124,125,126,127,128] when used as supporting ligands. This crucial increased π-acidity of CAACs, becomes even more pronounced via benzannulation of their 5 or 6-member scaffold (Figure 1(1C), fused Cyclic Aryl Alkyl Amino Carbenes; f-CArAC) [114,129,130,131], which due to conjugation further lowers the energy of this LUMO empty p-orbital. Variations in this latter scaffold featuring more than one nitrogen atom have also been reported [132,133,134].
Our attention was drawn to the two known f-CArAC (1C) salt precursors incorporating an auxiliary arene in the fused benzene ring [114], for which no known well-defined complexes have been reported. Therefore, we decided to pursue such ligand motifs to try and address this paucity. In this paper we report on the synthesis, isolation and characterisation of a small library of 1,1,2,4-tetraaryl-1H-isoindol-2-ium (n = 0) and 2,3,3,8-tetra(substituted)-3,4-dihydro-isoquinolin-2-ium (n = 1) carbene salt precursors ([f-CArAC-H]+X− (X = OTf−, [HCl2]−) incorporating such auxiliary arenes. We present aspects of their reactivity ultimately leading to the isolation and structural characterisation of the first f-CArAC: → Cu(I) complex featuring such a motif. As part of these studies, we also demonstrate the use of synthetic intermediates en-route to the afore-mentioned [f-CArAC-H]+X−salts to access iminium salts ([ACAC-H]+) and a 2,4,8-tri(substituted)-isoquinolin-2-ium salts, both of which are of interest as useful carbene precursors.

2. Materials and Methods

2.1. Reagents

All reactions were carried out using standard Schlenk and glovebox techniques unless otherwise stated. For air-sensitive reactions the solvents used were dried by refluxing under an inert atmosphere (N2) either over molten K (THF, n-hexane, toluene) or Na wire/benzophenone-ketyl (Et2O, n-pentane) for a minimum of three days and stored in Young’s or ROTAFLO ampules over activated 4 Å molecular sieves (the activation was performed using a heat-gun (ca 200 °C) under a dynamic vacuum until a stable vacuum ≤ 3 × 10−2 mbar was maintained). All other solvents were used as received and H2O was deionized. Column chromatography was performed using silica gel 0.035–0.07 mm, 60 Å purchased from Thermos Scientific, while TLC plates were from Macherey–Nagel (Alugram Xtra SIL G UV254). HCl 2.5 M solution in CPME (cyclopentyl–methyl-ether) was purchased from Acros in an AcroSeal bottle and was transferred upon arrival in a Young’s ampule and stored under N2 at 5 °C. Triflic anhydride (Tf2O) was purchased from Fluorochem and was transferred in a Young’s ampule upon arrival and stored at 5 °C under N2. Pd(PPh3)4 was purchased from Fluorochem and kept under N2 at 5 °C in a Schlenk flask. n-BuLi (2.5M solution in n-hexane) was purchased from Acros in an AcroSeal bottle and was stored in a glovebox freezer (−30 °C) under N2 and titrated prior to use. Benzophenone was sublimed, recrystallized from PE 40—60, dried and stored in an N2 filled glovebox at RT. Toluene-d8 (C7D8) was freeze-pump-thawed twice, before being refluxed in a Young’s amoule over molten K (120 °C) for a minimum of three days, followed by vac-to-vac transfer under static vacuum over activated 4 Å molecular sieves. All other chemicals and solvents were purchased from commercial sources and were used without further purification unless otherwise stated. The 2,6-dibromo-benzaldehyde was prepared according to the literature using EtOCHO instead of DMF. [135] Detailed syntheses of all compounds reported herein are provided in the ESI of this manuscript.

2.2. Spectroscopic and Analytic Techniques

1H, 13C{1H}, 19F NMR as well as correlation spectra were acquired on a Bruker Avance 400 (1H) NMR spectrometer. NMR spectra were referenced using the residual protio signals of the deuterated solvent (1H) or the signals of the solvent (13C{1H}), while in the case of 19F they were referenced externally relative to C6F6; all NMR spectra are reported using the δ scale (ppm). Where unambiguous assignment of resonances is possible, this is provided as per the numbering scheme of each compound in the ESI. IR spectra were recorded on a Shimadzu IRAffinity-1 spectrometer equipped with a QATR 10 single reflection ATR probe. HiRes mass-spectra were measured in ESI+ mode, using either a Brucker Maxis Impact QTOF spectrometer or an Agilent 6550 LC/Q-TOF equipped with an iFunnel sample introduction probe. All these data is provided free of charge in the ESI of this manuscript.

2.3. Single Crystal X-Ray Crystallography

Data for 5-H (CCDC: 2490407), 7-tBu (CCDC: 2490402), 10-CF3 (CCDC: 2490403), 12 (CCDC: 2490408), 14 (CCDC: 2490405), 15 (CCDC: 2490406) and 16 (CCDC: 2490404) were collected at the NKUA X-ray core facility on a dual source (IμS Diamond Cu/Κα and Mo/Κα) Bruker D8-Venture SC-XRD instrument equipped with a Photon-III area detector at 100K using an Oxford Cryosystems 100 cryostream. In the case of 5-H, 7-tBu, 12, 14, 16 and 17 data were collected using Cu/Κα to a resolution of 0.83 Å, while for 5-H to a resolution of 0.79 Å. For compounds 10-CF3 and 15 data were collected using Mo/Kα to a resolution of 0.70 Å.
Data collection was achieved using φ and ω scans to fill the Ewald sphere using a 4-circle kappa goniometer controlled by the APEX5 software package (version 2023.3.2 64-bit) which also handled subsequent processing. A multi-scan absorption correction (SADABS 2016/2) was applied in all cases.
Crystals were mounted on Mitigen cryo-crystallography loops from either dried vacuum-pump oil stored in a N2 filled glovebox over 4 Å molecular sieves (compound (15)) or silicon oil in air.
For the datasets of the compounds listed above, data solution (ShelXT, [136]) and subsequent model refinement (ShelXL, [137]) were achieved using the graphic interface of the Olex2-1.5 software package [138]. For the graphics of the molecular structures ORTEP-III was used [139].
All atoms were refined anisotropically and hydrogen atoms were added using the riding model, unless otherwise stated.
Special Refinement Details:
(7-tBu): The model was refined as an inversion twin with a BASF of 0.05. The model shows occupational disorder on one of the tert-butyl groups which was modelled using the PART command. The asymmetric unit contains a molecule of toluene situated at a special position showing occupational disorder over two positions as well as half a molecule of Et2O again at a special position also displaying the same disorder. These disorders were modelled using the PART command, while in the case of the disordered Et2O use of RIGU and ISOR restraints as well as an EADP constrain were necessary for a stable and conversing refinement.
(10-CF3): One of the CF3 substituents displays occupational disorder over two positions of two of its fluorine atoms. This was successfully modelled using the PART command with the occupancy of each site-let to refine freely and converge to a value of ca 60:40. A SADI restraint was used for the C-F distances of the minor part and its respective fluorine atoms were refined isotropically using an ISOR restraint.
(12): Three tert-butyl substituents show occupational disorder over two positions of their methyls (all three methyls for one of them and two of their methyls for the remaining). This was successfully modelled using the PART command with the occupancy of each site-let to refine freely and converge to values of ca 62:38, 72:28 and 86:14. Three of the carbons (C71A, C64A and C63A) belonging to the methyls in these minor parts, were refined isotropically using an ISOR restraint.
All other SC-XRD collection details and final refinement parameters are given in Tables S1 and S2 in the ESI.

3. Results and Discussion

3.1. Synthesis of f-CArAC Salt Precursors

The synthesis of the [f-CArAC-H]+X− salts and their precursors is summarised in Scheme 1:
The introduction of the auxiliary arene via the Suzuki coupling between 2,6-dibromo-benzaldehyde 1 and the appropriate arene boronic acid 2-R, is the first stage of the synthesis, and depending on 2-R, a mixture of the corresponding mono and di-substituted benzaldehydes 3-R and 4-R, in varying ratios, is formed (Table 1). Attempts to selectively prepare aldehydes 3-R, starting from 2-iodo-6-bromo-benzaldehyde, did not mitigate the formation of mixtures and were further hampered by the capricious synthesis [140,141] of this aldehyde, making it unsuitable for scale-up preparations. Introduction of other arenes such as 2,4,6-Me3-C6H2 and 3,5-F2-C6H3, albeit successful under these conditions, produced mixtures of 3-R and 4-R which were unfortunately inseparable by common laboratory methods. Attempts to solve this problem using Pd2(dba)3 in the presence of a Buchwald phosphine in a 1:1 ratio as the pre-catalyst did not fare any better and thus, they were not pursued any further.
Condensation of aldehydes 3-R with Dipp-NH2 (Dipp = 2,6-iPr2-C6H3) using ca 5% p-TSA.H2O as a catalyst in the presence of 4 Å molecular sieves in toluene at 120 °C under N2, furnishes imines 5-R in reasonable to excellent yields after column chromatography. Imine 5-H, has been previously reported to be used in the next steps of the synthesis of f-CArAC’s without further purification; in our case this proved problematic, but its purification at this stage is straightforward and resolved the issue. Other anilines (p-toluidine, 3,5-xylyl-amine and aniline) can also be introduced using these conditions but were not amenable to further purification due to their facile hydrolysis.
Starting from imines 5-R, the 1,1,2,4-tetraaryl-1H-isoindol-2-ium triflate [f-CArAC-H]+OTf− salt precursors 6 and 7-R can be accessed in low but re-producible yields via a one-pot procedure. This method has also allowed us to install a planar and non-flexible fluorene moiety in the spiro position of the 5-member heterocycle in the case of 6 by using 9-fluorenone instead of benzophenone. Imines 5-R can also act as versatile starting points for the preparation of 6-member f-CArAC salt precursors, as exemplified by 5-CF3 leading to the isolation of the 3,4-dihydro-isoquinolin-2-ium compound 8 as its HCl2− salt.
Unfortunately, attempts to further derivatise imines 5-R by using them as Suzuki coupling partners with CH2=CMe(BF3K) were unsuccessful, leading to intractable mixtures with some of the identified products resulting from C=N-Dipp bond hydrolysis or de-halogenation. Therefore, we opted to use aldehyde 3-tBu as a model for the Suzuki coupling with CH2=CMe(BF3K); indeed, this strategy proved successful yielding aldehyde 11 in a moderate isolated yield of 56%. The condensation reaction between 11 and Dipp-NH2, under the same conditions for the preparations of imines 5-R, proved sluggish and therefore an increase in catalyst loading to 10% of p-TSA.H2O was used. Surprisingly, this resulted in the one-step formation of the isoquinolin-2-ium tosylate heterocycle 12. A plausible mechanism for the formation of 12 is shown in Scheme 2 involving an intermediary imine and an allylic stabilised terminal carbon-cation to rationalise the formation of the 6-membered ring. When the reaction was repeated under the same conditions, but using a stoichiometric amount of p-TSA.H2O, compound 12 was not formed, and formation of [Dipp-NH3]OTs was observed instead.
We have also demonstrated the utility of the two by-products 4-H and 4-CF3 as precursors to access iminium salts 10-R, which we are currently investigating as precursors to access Acyclic Carbon Amino Carbenes [142,143,144,145,146]. Although the formation of their precursor imines 9-H/CF3 proceeds at reasonable yields, the following quarternisation step in the case of 10-CF3, is low yielding despite prolonged heating and elevated temperatures, most likely due to the electron-withdrawing CF3 substituents.

3.2. Characterisation of f-CArAC Salt Precursors

The afore-mentioned compounds and their precursors have been spectroscopically and analytically characterised. Their Hi-Res ESI+ mass spectra, show the parent [M]+ ion ([f-CArAC-H]+) or the [M+H]+ (precursor imines) or [M+Na]+ (precursor aldehydes) in good agreement with the theoretical values and isotopic envelopes. The NMR (1H, 13C{1H} and 19F) spectra of the reported [f-CArAC-H]X and iminium salts are consistent with an average Cs symmetry in solution. Table 2 and Table 3 summarise the 1H and 13C{1H} NMR chemical shifts in their characteristic protons and corresponding carbons.
It is worth pointing out that the organic cation in 12 possesses two sites (marked in red and blue) where potential deprotonation to generate a carbene can take place as reflected by their 1H-NMR chemical shift protons (see Figure S114 for their unambiguous assignment). The structure of the cation in 12 (vide infra) is redolent of a recently reported benzo[h]isoquinolinium salt prepared by Bertrand et al. [147], which upon deprotonation furnishes the corresponding pyridin-1-ylidene (i.e., equivalent to removal by base of the red hydrogen in 12+) that is in equilibrium with its pyridine-3-ylidene isomer (i.e., equivalent to deprotonation of the blue hydrogen in 12+), as evidenced by trapping experiments. We are currently exploring the deprotonation of 12 [148] especially since the increased steric hindrance imposed by the proximal bulky auxiliary arene could produce the corresponding isoquinolin-3-ylidene selectively.
The identity of compounds 7-tBu, 10-CF3 and 12 was also unambiguously confirmed by SC-XRD studies, and the molecular structures of their cations are shown in Figure 2.
The solid-state structures agree with their observed NMR spectra and are retained in solution. Their molecular structures exhibit no intra- or inter-molecular interactions between the counter anions and any of the hydrogen in the organic cations.

3.3. Attempts at Generating f-CArAC Free Carbenes and Synthesis of a Cu(I) Complex

Having successfully isolated the small library of [f-CArAC-H]+X− salts 6, 7-R (R = tBu, CF3) and 8 (Scheme 1), we proceeded with their deprotonation to generate and hopefully isolate the corresponding free carbenes. Unfortunately, our efforts using various bases (e.g., AN″ (A = Li+, Na+, K+; N″ = [N(SiMe3)3]−, LiNiPr2, KOtBu, LiTMP (TMP = 2,2.6,6-tetramethyl-piperidide) in THF or Et2O proved invariably unsuccessful, resulting in intractable mixtures even when the subsequent work-up was performed at low temperatures not exceeding −20 °C.
Jana and coworkers (in the case of CAAC’s) [149] and more recently Bertrand et al. (for f-CArAC’s) [150] have demonstrated that pyrrolidin-2-ols and isoindolin-1-ols (i.e., the products of H-OH addition at the corresponding carbene carbon respectively—Figure 1(1C)), can behave as carbene precursors upon heating with concomitant loss of water. Therefore, in view of our limited success with isolating free carbenes, we decided to explore this route in the presence of Cu(I)Cl to trap any in situ generated carbene. Salts 6 and 7-tBu were chosen as model compounds to test this hypothesis and gauge the effect of the auxiliary’s arene steric hindrance. The corresponding isoindolinols 13 and 14 can be easily synthesised via the reaction of 6 or 7-tBu, respectively, with either anhydrous NaOH in THF or KOH in a biphasic Et2O/KOH(aq) (0.2 M) system (Scheme 3).
Isoindolinols 13 and 14 have been characterised spectroscopically, analytically and, in the case of the latter, structurally as well. Their 1H-NMR and 13C{1H} spectra display a loss of the Cs symmetry observed in their parent compounds, characteristically evidenced by the succinct appearance of 4 doublets and two septets for the isopropyl substituents of the Dipp arene. Furthermore, the isoindol-2-ium protons (Table 2) for 6 (s, 9.45 ppm) and 7-tBu (s, 9.19) have shifted up-field to 6.70 ppm for 13 and 6.81 for 14, appearing as doublets due to coupling with the OH protons, and resonating at 2.18 ppm in 13 and 2.38 ppm in 14, with a 3JHH coupling of ca 4 Hz. Finally, the C1-N1 (Scheme 3) bond distance of 1.430(2) Å in the solid-state molecular structure of 14 is characteristic of a carbon nitrogen single bond.
Heating a solution of 13 in toluene in the presence of a small excess of Cu(I)Cl and 3Å molecular sieves at 100 °C in a Young’s ampoule overnight, causes a gradual colour change from pale yellow to deep red-purple. After filtration, removal of volatiles and washing with n-hexane to remove coloured impurities, a yellow residue is obtained, which after re-crystallisation from THF/n-hexane produced the desired Cu(I) complex 15 (Scheme 4) in 13–22% (depending on scale) isolated yields crystals suitable for an SC-XRD study (Figure 3).
The geometry around the two-coordinate Cu(I) metal centre in 15 is almost linear with the carbene carbon copper bond distance of 1.8800(12) Å equal within esd’s to the two previously structurally characterised f-CArAC: →Cu(I)-X complexes (X = Cl (1.879(3) Å [151]), Br (1.884(3) Å [152]; f-CArAC: = 2-[Dipp]-3,3-diphenyl-2,3-dihydro-1H-isoindol-1-ylidene, i.e., the analogous ligand bearing no auxiliary phenyl and incorporating two phenyls instead of a fluorene moiety), but longer than the derivatives of the latter where the halogen has been exchanged by another anionic ligand ([C5Me5]–: 1.845(2) Å; [C5H5]−: 1.8466(10); acac−: 1.848(2) Å; [acac(Ph)2]−: 1.8499(14) Å; pyrazolide: 1.8639(16) Å; acac = acetyl-acetonate) [152]. Based on the afore-mentioned metrics, the auxiliary arene in 15 does not seem to significantly affect the bonding in Cu(I) complexes supported by f-CArAC: donor ligands. Furthermore, the solid-state structure did not reveal any interaction between the Cu(I) metal centre and the auxiliary phenyl either intra- or inter-molecularly even in the packed unit cell in the case of the latter. Nevertheless, it is interesting to note that the phenyl ring projects towards the Cu(I) metal centre, with possible implications to its reactivity.
Complex 15 has also been spectroscopically characterised, with its 1H and 13C{1H} NMR spectra being consistent with the determined solid-state structure that is retained in solution, and the carbene carbon (i.e., C1 in Figure 4) resonating at 232.3 ppm (δ(C6D6)) in the 13C{1H} NMR spectrum, in agreement with previous literature examples [129,151,152].
The isolation of complex 15, is a good indication of the in situ formation of the f-CArAC: carbene via the thermally induced dehydration of the corresponding isoindolinol 13. In view of the low isolated yield of 15, we decided to follow the reaction in C7D8, under otherwise similar conditions. After 2 h of heating the 1H-NMR spectrum of an aliquot from the reaction mixture revealed that a small amount of 15 had already formed (ca 5% based on relevant integration of Dipp resonances), along with unreacted 13 and a new species 16 at a 3:1 approximate ratio, respectively, based on their relative integration (Figure S145 in ESI). Almost complete consumption of 13 was observed after ca 22 h, with the two identifiable species (Figure S146 in the deep red-purple solution being the Cu(I) complex 15 and the new species 16 (Scheme 4). After work-up, the identity of 16 was unambiguously confirmed via a SC-XRD study (Figure 4) on crystals grown from a saturated Et2O solution of the insoluble in n-pentane solids (which also contain complex 15).
Imine 16 (N1-C1 bond distance of 1.2586(19) Å) is the result of ring contraction with a plausible mechanism for its formation shown in Scheme 5. This involves the generation of the free carbene 13C: [153], followed by the formation of a substituted vinylidene-λ2-azane that subsequently undergoes the observed ring contraction in a similar manner to that recently posited by Bertrand and coworkers [150]. Indeed, when 13 is heated in the absence of Cu(I)Cl, formation of 16 is observed in >90% spectroscopic yield (Figure S142 in the ESI). Together these results advocate for the formation of 13C: as a fleeting species in solution. We are currently investigating alternative reaction conditions to suppress the formation of 16 by increasing the rate of trapping of 13C: by a metal centre.
When isoindolin-1-ol 14 (Scheme 3) was heated in a similar manner as above, either in the presence or absence of Cu(I)Cl, then the same colour changes were observed, but no well-defined products could be isolated. This suggests that steric hindrance plays a crucial role, and we are currently working on introducing less bulky arenes on the N-heteroatom.

4. Conclusions

In summary we report on the successful synthesis and isolation of a small library of new fused Cyclic Aryl Amino Carbene salt precursors, functionalized with an auxiliary arene situated on the annulated benzene ring. We have used Suzuki cross-couplings, using commercially available 2,6-dibromo-benzaldehyde, as the key step to introduce various arenes and consequently access various scaffolds, including two new Acyclic Aryl Amino Carbene salt precursors and an unexpected isoquinolin-2-ium salt. Although, access to the corresponding carbenes has been elusive, their in-situ generation from the thermal dehydration of isoindolin-1-ols is further documented by, (a) a trapping experiment resulting in the isolation of a new Cu(I) complex and (b) the isolation of a ring contraction product. We are currently expanding on the insights offered by these results and our efforts will be reported in a forthcoming publication.

Supplementary Materials

Schemes S1-S16: Synthesis of compounds reported here-in; Figures S1–S146: Spectroscopic (NMR, IR) data of compounds reported herein; Tables S1&S2: Collection and model refinement details of SC-XRD studies for compounds 5-H, 7-tBu, 10-CF3, 12, 14, 15 and 16. The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/org6040051/s1, Crystallographic information files (.cif) of compounds 5-H, 7-tBu, 10-CF3, 12, 14, 15 and 16 have been deposited at the CCDC; these data is free of charge. References [154,155,156] are cited in the Supplementary Materials.

Author Contributions

Conceptualization, N.T.; methodology, N.T. and P.C.I.; synthesis, P.C.I., N.T.; SC-XRD collection, solution and model refinement, N.T.; formal analysis, P.C.I. and N.T., Hi-Res Mass-spec, S.-P.K.; writing—original draft preparation, P.C.I. and N.T.; writing—review and editing, P.C.I. and N.T.; project administration, N.T.; funding acquisition, N.T. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded within the framework of the National Recovery and Resilience Plan Greece 2.0, funded by the European Union–NextGenerationEU, as implemented by the Hellenic Foundation for Research and Innovation (H.F.R.I.), grant number 15293 (acronym CEPTr).

Data Availability Statement

The original contributions presented in this study are included in the article/Supplementary Materials. Further inquiries can be directed to the corresponding author.

Acknowledgments

Access to the SC-XRD instrumentation in the National and Kapodistrian University of Athens Core Facility is greatly acknowledged. The authors are also grateful to C. Mantzourani and N. Stini for Hi-Res mass spectra acquisition and A. A. Danopoulos for helpful discussions, access to glovebox facilities and a generous loan of anhydrous Cu(I)Cl.

Conflicts of Interest

The authors declare no conflicts of interest.

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Figure 1. Representative NHC architectures (1A) (top); Reported scaffolds of CAACs (1B) (below) and f-CArACs (1C); the grey ethylene bridge denotes bicylic CAACs where no R1′, R2′ are present.
Figure 1. Representative NHC architectures (1A) (top); Reported scaffolds of CAACs (1B) (below) and f-CArACs (1C); the grey ethylene bridge denotes bicylic CAACs where no R1′, R2′ are present.
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Scheme 1. Synthetic routes to [f-CArAC-H]+X− salt precursors (isolated yields).
Scheme 1. Synthetic routes to [f-CArAC-H]+X− salt precursors (isolated yields).
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Scheme 2. Plausible mechanism leading to salt 12.
Scheme 2. Plausible mechanism leading to salt 12.
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Figure 2. From left to right: ORTEP-III diagrams of the molecular structures of the cations in 7-tBu, 10-CF3 and 12, respectively, displaying 50% ADP’s; counter-anions, co-crystallisation solvent (C7H8 and Et2O in the case of 7-tBu, CH3CN in the case of 10-CF3 and H2O in the case of 12) and most H atoms have been omitted for clarity (colour code: black: carbon; blue: nitrogen; green: fluorine; wheat: hydrogen).
Figure 2. From left to right: ORTEP-III diagrams of the molecular structures of the cations in 7-tBu, 10-CF3 and 12, respectively, displaying 50% ADP’s; counter-anions, co-crystallisation solvent (C7H8 and Et2O in the case of 7-tBu, CH3CN in the case of 10-CF3 and H2O in the case of 12) and most H atoms have been omitted for clarity (colour code: black: carbon; blue: nitrogen; green: fluorine; wheat: hydrogen).
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Scheme 3. Synthesis of isoindolinols 13 and 14 and ORTEP-III diagram of the molecular structure of 14 (50% ADP’s); C1-N1: 1.430(2) Å.
Scheme 3. Synthesis of isoindolinols 13 and 14 and ORTEP-III diagram of the molecular structure of 14 (50% ADP’s); C1-N1: 1.430(2) Å.
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Figure 3. ORTEP-III diagram of the molecular structure of Cu(I) complex 15 showing 50% ADP’s with H atoms omitted for clarity. Selected bond distances (Å) and angles (°): Cu1-Cl1: 2.1144(3), Cu1-C1: 1.8800(12), N1-C1: 1.3190(16), C1-Cu1-Cl1: 171.20(4).
Figure 3. ORTEP-III diagram of the molecular structure of Cu(I) complex 15 showing 50% ADP’s with H atoms omitted for clarity. Selected bond distances (Å) and angles (°): Cu1-Cl1: 2.1144(3), Cu1-C1: 1.8800(12), N1-C1: 1.3190(16), C1-Cu1-Cl1: 171.20(4).
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Scheme 4. Concurrent formation of Cu(I) complex 15 and the ring contraction by-product 16.
Scheme 4. Concurrent formation of Cu(I) complex 15 and the ring contraction by-product 16.
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Figure 4. ORTEP-III diagram of the molecular structure of 16 showing 50% ADP’s with H atoms omitted for clarity.
Figure 4. ORTEP-III diagram of the molecular structure of 16 showing 50% ADP’s with H atoms omitted for clarity.
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Scheme 5. Plausible mechanism explaining the formation of 16.
Scheme 5. Plausible mechanism explaining the formation of 16.
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Table 1. Relative ratio of mono- (3-R) and di-arene (4-R) substituted benzaldehydes based on the relative integration of their CHO protons (400 MHz) in the crude reaction mixture.
Table 1. Relative ratio of mono- (3-R) and di-arene (4-R) substituted benzaldehydes based on the relative integration of their CHO protons (400 MHz) in the crude reaction mixture.
R3-R/4-R
H1/0.27
tBu1/0.13
CF31/0.71
Table 2. Characteristic 1H (400 MHz) and 13C{1H} (100.6 MHz) NMR chemical shifts for the cations in 6, 7-R and 8.
Table 2. Characteristic 1H (400 MHz) and 13C{1H} (100.6 MHz) NMR chemical shifts for the cations in 6, 7-R and 8.
CompoundOrganics 06 00051 i001Organics 06 00051 i002Organics 06 00051 i003
1H-NMR chemical shift (δ(CDCl3))9.459.19 (R = tBu)
9.30 (R = CF3)		8.11
13C{1H}-NMR chemical shift (δ(CDCl3))175.01173.77 (R = tBu)
175.08 (R = CF3)		166.20
Table 3. Characteristic (400 MHz) and 13C{1H} (100.6 MHz) chemical shifts for the cations in 10-R and 12.
Table 3. Characteristic (400 MHz) and 13C{1H} (100.6 MHz) chemical shifts for the cations in 10-R and 12.
CompoundOrganics 06 00051 i004Organics 06 00051 i005
1H-NMR chemical shift (δ(CDCl3))11.16 (R = H)
10.23 (R = CF3)		8.67
8.58
13C{1H}-NMR chemical shift (δ(CDCl3))185.44 (R = H)
184.26 (R = CF3)		135.37
145.78
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Ioannou, P.C.; Tsoureas, N.; Kotsaki, S.-P. Synthesis of Fused Cyclic Aryl Amino Carbon Carbene Salt Precursors ([f-CArACH]+) Incorporating an Auxiliary Arene and Isolation of a Cu(I) Complex. Organics 2025, 6, 51. https://doi.org/10.3390/org6040051

AMA Style

Ioannou PC, Tsoureas N, Kotsaki S-P. Synthesis of Fused Cyclic Aryl Amino Carbon Carbene Salt Precursors ([f-CArACH]+) Incorporating an Auxiliary Arene and Isolation of a Cu(I) Complex. Organics. 2025; 6(4):51. https://doi.org/10.3390/org6040051

Chicago/Turabian Style

Ioannou, Polidoros Chrisovalantis., Nikolaos Tsoureas, and Sevasti-Panagiota Kotsaki. 2025. "Synthesis of Fused Cyclic Aryl Amino Carbon Carbene Salt Precursors ([f-CArACH]+) Incorporating an Auxiliary Arene and Isolation of a Cu(I) Complex" Organics 6, no. 4: 51. https://doi.org/10.3390/org6040051

APA Style

Ioannou, P. C., Tsoureas, N., & Kotsaki, S.-P. (2025). Synthesis of Fused Cyclic Aryl Amino Carbon Carbene Salt Precursors ([f-CArACH]+) Incorporating an Auxiliary Arene and Isolation of a Cu(I) Complex. Organics, 6(4), 51. https://doi.org/10.3390/org6040051

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