General Access to Acenaphthene-Fused N ‑ Heterocyclic Carbene Ligands

: We communicate a general method for the syntheses of acenaphthene-fused imidazolinium salts that are direct precursors to augmented N -heterocyclic carbenes with a fixed cis geometry. Reduction of bis(imino)acenaphthene ligands with a LiAlH 4 /AlCl 3 reagent mix initially produced the corresponding 1,2-diamines which, upon ring-closing reaction with triethyl orthoformate in acidic solution, gave the requisite ionic intermediates. Formation of the carbenes was then shown by preparation of selected [Cu(NHC)] complexes that were obtained via treatment of the respective imidazolinium salt with base in the presence of a Cu(I) source.


■ INTRODUCTION
The first reports on bis(imino)acenaphthenes (BIANs) date back to the late 1960s, 1 but since then, this double Schiff base class languished in obscurity for almost three decades until the topic was invigorated by the Elsevier group in the beginning of the 1990s. 2 Later, Ragaini and co-workers devised more general, high-yielding synthetic procedures that also addressed the preparation of naphthalene-fused α-diimines equipped with electron-withdrawing substituents, 3 mixed Ar, Ar'-BIANs, 4 and some more elusive cycloalkyl derivatives. 5 BIAN chelators bind to a vast array of main group metals 6 as well as transition elements, 7 and catalytic applications 8 of the respective complexes encompass (base-)metal-catalyzed hydrogenations, 9 CO-mediated nitroarene reductions, 10 hydroaminations, 11 (light-driven) C−C bond formations, 12 and ethene polymerization reactions that are well-known for their high importance in certain industrial settings. 13 Further areas include selected oxidation reactions 14 with t-BuOOH or H 2 O 2 as stoichiometric oxidants and, moreover, soluble BIAN complexes incorporating Fe or Co proved to be amenable to heterogenization via controlled pyrolysis in order to obtain solid catalysts that effect the important nitro-to-aniline reduction with H 2 gas. 15 Besides the ready adjustment of their stereoelectronic properties through rational choice of the respective aniline precursor, 3 the structural malleability of the BIANs adds further benefits to this ligand class. In this regard, ring closure mediated by MeOCH 2 Cl produces the respective imidazolium salt, which is an immediate precursor to the corresponding acenaphthylene-fused N-heterocyclic carbene (BIAN-NHC). 16 Thus, the pertinent α-diimines are readily converted, via a brisk two-step sequence, into excellent σ-donors that function as reliable spectator ligands. 17 The first report on a free, isolable NHC by Arduengo 18 triggered extensive research into metal carbene catalysis which, in turn, ushered in an era of fruitful competition between NHCs and the then-dominating phosphine ligands. 19 Numerous preparative efforts have produced an entire smorgasbord of NHC-based catalysts that facilitate diverse chemical transformations such as hydrogenations, hydrosilylations, couplings, and olefin metathesis reactions. 20 With reference to the latter, the replacement of phosphine with imidazolidine-derived carbene in Grubbs' original catalysts dramatically improved the performance, with rates up to 1000 times faster than the all-phosphine type. 21 A further striking example of carbene catalysis is an in-situ-formed [Ni(NHC)] complex that enables the hydrogenative cleavage of aryl ethers, 22 thus showing promising potential for the syntheses of valuable chemicals from forest-derived, inedible resources such as lignin.
Referring back to imidazole-derived carbenes that are additionally buttressed by a rigid acenaphthylene backbone, these BIAN-NHCs significantly capitalize upon the intrinsic stabilization that is provided by the flanking π-system and, in addition, conjugative contact with the BIAN skeleton ameliorates the σ-donor capability of the carbene donor atom. Finally, the intimate linkage to the flat, unsaturated hydrocarbon subunit is thought to foster the steric fineadjustment of the catalytically active pocket by forcing the Naryl substituents into close proximity to the active metal center. 23 Apart from the engagement in a ring−closing reaction, the BIAN diimine motif can also undergo reduction to afford the corresponding enediamine (BIANH 2 ) 24 or the related diamine (BIANH 4 ) 25,26 (Scheme 1). Although BIANH 2 s represent compounds of separate physical existence, they are heavily prone to oxidation and hence these potential bidentate ligands cannot be stored for a longer period of time without getting reoxidized to the parent BIAN. In stark contrast, the BIANH 4 s are easily weighable solids that are readily handled on the bench top and, notably, proper choice of the substitution pattern allows for the design of chiral compounds for both diastereomers. Very interestingly, literature reports on BIANH 4 -type diamines are limited to 2,6-diisopropylphenyl-, mesityl-, and tolyl-substituted derivatives. Therefore, we chose to develop a comprehensive reduction protocol for the syntheses of BIANH 4 ligands that also accommodates the presence of heteroatoms in the N,N′-substituents such as halides, methoxy, or trifluoromethyl (vide infra).
Generally, a very important feature of vicinal diamines is their convertibility into the corresponding imidazolinium salt upon treatment with triethyl orthoformate (TEOF) in acid. 27 Herein, we adopted this approach for the synthesis of a set of (mostly) unprecedented acenaphthene-fused NHC precursors with fixed cis configuration (Scheme 2, left panel). Worthy of note, the installation of an unsymmetrical substitution pattern about the BIANH 4 diamine moiety opens the intriguing possibility of making new chiral NHC complexes that might catalyze important chemical transformations such as hydrogenation reactions (vide supra). Yet, upon using TEOF/H + , formation of the respective trans-annulated NHC is not feasible owing to the intrinsic, prohibitively high ring strain in the bicyclic subunit of the fused heterocycle (Scheme 2, right panel).

■ RESULTS AND DISCUSSION
Since reports on the preparation and characterization of BIANH 4 s are limited to three alkylphenyl-substituted derivatives (vide supra), 25,26 we initially tried to reduce BIANs that lie outside this rather narrow scope and which therefore include electron-withdrawing groups (halides, CF 3 ) as well as donors (RO). Several common metal hydrides were tested as reducing agents (NaBH 4 , LiBH 4 , NaCNBH 3 , Red-Al, and LiAlH 4 ), but all reactions proceeded only sluggishly, and the sought-after diamine was, if it had formed at all, only detected in minuscule quantities. In general, after the addition of the reductant to the dissolved BIAN, we observed the formation of a deeply colored solution that pointed toward the formation of substantial amounts of the corresponding enediamine-type BIANH 2 ; whenever these reaction solutions had been aerated, the original color was restored, which indicated adverse backoxidation of the enediamine to the starting BIAN.
Yet, initial failures concerning the BIANH 4 formation were effectively countered upon pairing LiAlH 4 with a proper Lewisacidic companion reagent, i. e., AlCl 3 , thus permitting in situ generation of alane (AlH 3 ). 28 Since the central Al atom in the latter is devoid of an octet, the reactivity of AlH 3 is superior in comparison with those of commercial metal-based hydrides. 29 Rewardingly, the alane so obtained was directly applicable to the pertinent [Zn(BIAN)] complexes 1, and therefore the inefficient and time-consuming demetallation step 3 to liberate the free BIAN ligand could be excluded in the preparation of the projected BIANH 4 s 2 (Scheme 3). The acenaphthenefused diamines thus-produced were either isolable as the free base or as the respective hydrochloride salt through precipitation with HCl from a saturated DCM solution in order to obtain colorless or off-white microcrystalline powders. Importantly, the desired cis-fused diamine 2 was, depending on the substitution pattern, contaminated with varying amounts of the unwanted trans isomer rac-trans-2 in most cases. However, since the ensuing ring-closing reaction with TEOF/H + is not viable with the trans diamines (vide supra), it was not necessary to separate both diastereomers prior to the syntheses Organometallics pubs.acs.org/Organometallics Article of the imidazolinium salts 3-HCl or 3-HBF 4 as the bis(formamide) side products rac-trans-2-(CHO) 2 were easily removed from the reaction mixture. While most of the tested BIAN ligands were neatly converted into their BIANH 4 derivatives, the syntheses of CF 3 -tagged diamines 2y and 2aa as well as the preparation of dimethylamino congener 2ac were severely hampered (Scheme 4). With respect to the o-and p-CF 3 BIAN reduction, unselective hydrodefluorination occurred but, in the latter case, application of a large excess of AlH 3 enabled full reduction of the trifluoromethyl group to selectively obtain the corresponding p-tolyl compound 2c. Surprisingly, related reductions that aimed at the preparation of the full set 2k-x were largely free from detrimental hydrodehalogenation processes. Regarding the unsymmetrical 2ak and the cyclopropyl derivative 2al, the reaction had to be quenched at −5°C so as to leave the sensitive substituents (quinoline and strained cyclopropyl, respectively) untouched. Strikingly, in case of the reduction of the bis(cyclopropyl)-BIAN, application of a higher AlH 3 loading and prolonged reaction time permitted a convenient route to achieve the elusive N,N′-di-n-propyl BIANH 4 2am, which is not directly accessible from the parent BIAN because bis(alkyl)-BIANs are notoriously unstable. 3,7d As mentioned above (Scheme 1), the reduction of αdiimines with metal hydrides produces a diastereomeric mixture of vicinal diamines in which the cis/trans ratio is heavily dependent upon the BIAN substitution pattern and the nature of the solvent. In accordance with the literature, we found that BIANH 4 s 2f and 2i were almost exclusively obtained in the cis configuration. Interestingly, while the p-tolyl kindred 2c was previously reported to predominate in the trans configuration, 24 the in situ AlH 3 method described herein afforded the same compound, almost exclusively, in the cis form. Of note, the hitherto unknown diamines 2e, 2j, and 2q were also mainly cis despite their steric encumbrance in vicinity of the reacting C�N motif. On the other hand, the BIANH 4 s 2ad and 2ag bearing ortho methoxy groups were largely trans configurated.
The influence of the solvent on the diastereomeric ratio is best exemplified in the case of 2a that was isolated in a cis/ trans ratio of 20:80 when running the reaction in pure diethyl ether, whereas an Et 2 O−THF mixture (2:1 by volume) gave rise to a transposed 90:10 mixture. A similar, pronounced With a series of structurally diverse BIANH 4 s in hand, we went on to synthesize the corresponding annulated imidazolinium salts 3-HCl and 3-HBF 4 , respectively (Scheme 3). For the former, we adhered to the guidelines from a precedent literature protocol 27 that encompasses the following: (1) the conversion of the diamine into the hydrochloride salt with etheric HCl solution (2 M) followed by (2) heating the latter in HC(OEt) 3 (triethyl orthoformate, TEOF) in the presence of HCOOH. However, when we initially performed the ringclosing reaction, as recommended, in the presence of formic acid, we found that the desired salts 3-HCl were, in many cases, contaminated with the corresponding imidazolidines 3-H (Scheme 3). The latter were formed upon reduction of the imidazolinium species with HCOOH which, in addition to its Organometallics pubs.acs.org/Organometallics Article anticipated role as a Brønsted acid, obviously also functioned as a transfer hydrogenation agent. Consequently, we decided to leave out the formic acid catalyst and, henceforth, the imidazolinium salt formation was not further obstructed by detrimental side reactions (Scheme 5). Importantly, the trans isomers of the diamines 2 produced bis(formamides) rac-trans-2-(CHO) 2 (Scheme 3) that remained in solution under the reaction conditions, whereas the projected heterocyclic salts 3-HCl precipitated as microcrystalline, easy-to-separate solids. In general, the ring closure is indifferent with regard to the stereoelectronic properties of the BIANH 4 aryl substituents provided they are placed in the meta or para position of the ring whereat most of the yields well exceeded the 90% mark; only the bis-CF 3 -substituted salt 3ab-HCl was not formed under the reaction conditions, presumably owing the very strong electron-withdrawing effect of both trifluoromethyl groups.
Yet, the steric demand of the ortho substituents greatly affected the outcome of the reaction. In this context, bulky and branched alkyl groups (3i-, 3j, and 3an-HCl) as well as sterically demanding halides (3q-, 3s-, and 3v-HCl) greatly inhibited the formation of the desired N-heterocyclic salts. Only the fluoro group seemed to be small enough to not impair the ring-closing reaction en route to 3k-HCl.
The sterically congested 2,6-diisopropyl derivative 2i did not undergo heterocycle formation using this two-step hydrochloride method. Notwithstanding this experimental finding, it was reported earlier that the related tetrafluoroborate salt 16 Scheme 5. BIANH 4 -Derived Imidazolinium Chlorides 3-HCl Obtained on Application of General Procedure GP2 (see the Experimental Section) With the Stated Reaction Conditions a a The yields were calculated for the ring closure with respect to the amount of the cis isomer in the starting material 2·2 HCl. The reaction mixture was heated to 100°C; purification procedure used is described in detail in the Supporting Information.

Organometallics pubs.acs.org/Organometallics
Article was readily obtained upon the reaction of diamine 2i with NH 4 BF 4 in neat TEOF. In order to expand upon the substrate scope outlined in Scheme 5, we applied this NH 4 BF 4 /TEOF method to the diamines that were not converted into the tagged imidazolinium salts via the diamine·2 HCl route. Indeed, all, but one (3j-HBF 4 ), NHC precursor salts that were hitherto not accessible were obtained in fairly good yields (77−98%) on adoption of the slightly different tetrafluoroborate approach (Scheme 6). Importantly, also chiral, quinoline-functionalized 2ak was smoothly transformed into the desired ionic heterocyclic compound 3ak-HBF 4 .
Since N-heterocyclic carbenes are well-known to engage in the formation of stable organometallics when attached to coinage metals 30 including abundant copper, 31 we chose to prepare selected Cu(I) complexes that incorporate our ownsynthesized, acenaphthene-supported NHCs. Our decision was further guided by the fact that pertinent carbene-modified copper hydrides show interesting reaction patterns in catalytic redox transformations. 32 In this connection, Teichert and coworkers recently demonstrated that a bifunctional NHC ligand gives rise to a CuH species with inverted reactivity. Typically, complex copper hydrides such as Stryker's reagent 33 are soft nucleophiles that effect, inter alia, the 1,4-reduction of enoates. Yet, the NHC motif pertaining to the Teichert system renders the metal hydride rather hard so as to enable the valuable and challenging ester-to-alcohol hydrogenation. 34 Treatment of the precursor salts (3-HCl, 3-HBF 4 ) with the respective copper(I) halide (CuCl, CuBr) in the presence of K 2 CO 3 in DCM or acetone furnished the desired coordination compounds in acceptable (55% for 3ah-CuCl) to very good yields (89% for 3q-CuCl), as summarized in Scheme 7. Quite remarkably, putting strongly electron-withdrawing functionalities (halides, CF 3 ) in the meta or para position of the N,N′diphenyl portion of the NHC unit caused a sharp decline in the electron density of the carbene C atom such that it became susceptible to nucleophilic attack by water. 35 As a result, the initially formed Cu carbene complex promptly decomposed to the respective formamide 2-CHO (Scheme 7). Noteworthily, the presence of H 2 O was not avoided since it is generated as a by-product from the deprotonation of the imidazolinium salt with the carbonate base. However, substituents placed in the ortho position did not interfere with the formation of the wanted metal complexes, irrespective of the stereoelectronic properties of the substituent(s). Obviously, the tested substituents that were situated next to the carbene C provided a potent barrier against intruding water. The 2-adamantylsubstituted 3an-CuCl was not obtained through this procedure since the precursor 3an-HBF 4 was not deprotonated by Scheme 6. BIANH 4 -Derived Imidazolinium Tetrafluoroborates 3-HBF 4 Prepared Upon Reaction of Diamines 2 with NH 4 BF 4 in TEOF According to General Procedure GP3 (see the Experimental Section) a a Reaction mixture was heated to 115°C; heating to 140°C led to the formation of TEOF adduct 3ab-TEOF-BF 4 ; b Reaction mixture was heated to 125°C; c General Procedure GP3 was slightly adjusted (Supporting Information). Organometallics pubs.acs.org/Organometallics Article K 2 CO 3 . Even by switching to a stronger base using NaOtBu, we were unable to isolate the copper complex. Finally, Figure 1 captures the molecular structure of three selected complexes 3h-CuCl, 3af-CuBr, and 3af-CuCl as determined by single crystal X-ray diffraction analysis. These structural diagrams clearly indicate the cis fusion of the acenaphthene backbone that is linked to the imidazolinium core. Moreover, the high tendency of the Cl ligand to bridge two metal centers 29 is confirmed provided that steric congestion is eliminated (mononuclear 3h-CuCl vs binuclear 3af-CuCl).

■ CONCLUSIONS
We introduced a general method for the syntheses of acenaphthene-based, vicinal diamines that were prepared through reduction of the respective BIAN ligand with AlH 3 that was prepared in situ from LiAlH 4 and AlCl 3 . The stereochemistry of the thus-obtained BIANH 4 chelators was elucidated by NMR spectroscopy, X-ray crystallography, and chiral HPLC upon which they were subjected to ring-closing reactions brought about by treatment of the amines with triethyl orthoformate aided by HCl or HBF 4 . This approach permitted access to cis-fused, acenaphthene-tagged imidazolinium salts that are viable precursors to augmented Nheterocyclic carbene ligands. Since NHC-functionalized CuH complexes are promising hydrogenation catalysts with interesting reactivity patterns, we synthesized a series of Cu(I) complexes that incorporated our own-developed BIANH 4 -derived carbene motif. These copper-based organometallics were readily assembled upon reaction of the pertinent imidazolinium salt with K 2 CO 3 in DCM or acetone at slightly elevated temperatures.
The potential of the acenaphthene-fused NHC ligands to aid in (base-)metal-catalyzed hydrogenation reactions, including enantioselective syntheses, is currently explored in our research laboratories.

■ EXPERIMENTAL SECTION
General Experimental Considerations. Chemicals were purchased from Alfa Aesar, Fisher Scientific (including Acros Organics), Merck (including Sigma-Aldrich), TCI, or VWR and were used as received without further purification (except for acenaphthene quinone; see the purification procedure below). Anhydrous ZnCl 2 was stored in a tightly sealed flask and was quickly weighed under air; deuterated solvents were purchased from Deutero GmbH, and dry solvents were either purchased or purified by an M. BRAUN Solvent Purification System SPS-7. Reactions under inert conditions were carried using standard Schlenk technique with either N 2 (5.0) or Ar (5.0) from Linde Gas GmbH. If not specifically stated, the reactions were performed without any protection from air.
NMR data were collected on a Bruker AVANCE 300 MHz spectrometer and the measurements at temperatures other than r.t. were recorded on a Bruker AVANCE 500 MHz spectrometer. Chemical shifts are given in parts per million (ppm) on the delta (δ) scale and are referenced to residual solvent signals according to the literature. 36 IR spectra were recorded on a Bruker ALPHA II FT-IR Scheme 7. Set of Unprecedented [Cu(NHC)] Complexes 3-CuX (X = Cl or Br) that are Buttressed by an Acenaphthene Core Organometallics pubs.acs.org/Organometallics Article spectrometer with a monolithic diamond crystal and a platinum ATR module. Chiral chromatography was performed on a Shimadzu LC-20 HPLC system with UV detection using a YMC CHIRAL ART cellulose-SB 5 μm column. Purification of Acenaphthenequinone. Commercial acenaphthenequinone tends to appear as an ochre-colored powder containing significant amounts of impurities. For the purification, acenaphthene quinone (12 g) was suspended in DCM (1000 mL) and stirred for 1 h whereupon the suspension was filtered through a plug of silica. On removing the solvent under reduced pressure, the acenaphthenequinone was obtained as fine, needle-shaped yellow crystals (9.5 g).
Synthesis of BIAN Derivatives and ZnCl 2 Complexes (1/1-ZnCl 2 ). Most of the BIAN ligands and their ZnCl 2 complexes were prepared in accordance with the literature protocols; the procedural details are delineated in the Supporting Information.
General Procedure 1 (GP1): Synthesis of Acenaphthene-1,2-Diamines (2). Under a N 2 atmosphere, dry diethyl ether (18 mL) was filled into a 100 mL Schlenk flask and cooled with an ice bath. Hereafter, AlCl 3 (400 mg, 3 mmol, 1 equiv) was added following which the suspension was stirred for a period of 10 min. Then, 1 M LiAlH 4 in THF (9 mL, 9 mmol, 3 equiv) was added, and the mixture was cooled to −70°C using an isopropanol/liquid N 2 mixture. After the addition of solid 1/1-ZnCl 2 (3 mmol, 1 equiv), the reaction mixture was agitated overnight, thereby allowing it to slowly reach RT. After that, methanol was added dropwise under manual stirring until the gas evolution had ceased (diethyl ether was occasionally added whenever the entire content of the flask had solidified). All volatiles were then removed under reduced pressure whereupon the residue was dried in vacuo for 1 h. The solid was ground with a pestle and extracted with DCM (2 × 100 mL). Subsequently, the suspension was filtered over Celite 545 in a Buchner funnel whereat the obtained filter cake was washed with DCM (20 mL).
Isolation Method B. The filtrate was concentrated under reduced pressure to 10 mL whereupon 2 M HCl in Et 2 O (4.5 mL, 9 mmol, 3 equiv) was added. After the addition of neat diethylether (20 mL), the suspension was stirred for a period of 10 min at RT. The formed precipitate (2·2 HCl) was collected on a Buchner funnel, washed with diethyl ether (2 × 10 mL), and eventually dried in vacuo.
General Procedure 2 (GP2): Synthesis of Imidazolinium Chlorides . The respective diamine 2 (1 equiv) was suspended/dissolved in a small volume of DCM whereupon 2 M HCl in Et 2 O (3 equiv) was added while stirring. Neat diethyl ether (15 mL) was added, and the formed precipitate (2·2 HCl) was collected on a Buchner funnel, washed with diethyl ether (2 × 10 mL), and then dried in vacuo.
The hydrochloride salt 2·2 HCl (1 eq.) was suspended in triethyl orthoformate (20−60 equiv), and then the mixture was heated at 135°C in an Ar-flushed distillation apparatus for a period of 10 min in order to drive out the ethanol that is formed during the formation of the heterocycle. The obtained solid (3-HCl) was collected on a Buchner funnel while the mixture was still warm (50°C) to avoid any coprecipitation of bis(formamide), washed with diethyl ether (2 × 10 mL), and finally dried in vacuo.
General Procedure 4 (GP4): Synthesis of Copper(I)−NHC Complexes . For the preparation of 3-CuX, a modified literature procedure was employed. 37 Under an argon atmosphere, a dry Schlenk tube was charged with 1 equiv of 3-HCl or 3-HBF 4 , 2 equiv of CuCl (CuBr for 3af-CuBr), and 3 equiv of K 2 CO 3 . Dry acetone (1.5 mL per 100 mg of imidazolinium salt) was then added, and the mixture was stirred at 60°C for a period of 16 h. Afterward, DCM was added, and the mixture was sonicated to dissolve the product. Subsequently, the mixture was filtered through a 1 × 3 cm plug of silica, which was rinsed three times with DCM. The filtrate was concentrated to 2 mL, and the product was precipitated/ crystallized upon addition of diethyl ether. Finally, the solid was collected on filter paper, washed with diethyl ether, and dried in vacuo.
For the carbene complexes 3ah-CuCl and 3ai-CuCl, dry DCM was used instead of acetone whereby the reaction was conducted in a pressure tube.
Procedure for the BIAN ligand syntheses and ZnCl 2 complexes thereof; 1 H, 13 C, and 19 F NMR spectra; HRMS spectra; ATR-IR spectra; HPLC chromatograms; and X-ray crystallographic data (PDF)