Sc3N@Ih-C80 as a novel Lewis acid to trap abnormal N-heterocyclic carbenes: the unprecedented formation of a singly bonded [6,6,6]-adduct

An unprecedented singly bonded [6,6,6]-adduct with an abnormal N-heterocyclic carbene structure, represents the first example of carbon-based Lewis acid–base pairs based on endohedral metallofullerenes.


Introduction
"Frustrated Lewis pairs" are promising metal-free catalysts to activate small molecules such as H 2 , CO 2 , alkenes and alkynes. [1][2][3] Carbon-based Lewis bases are naturally diverse, such as ylides, isonitriles, enamines and N-heterocyclic carbenes (NHCs). 4 Among them, NHCs as stable carbene compounds featuring a neutral divalent carbon atom with two non-bonding electrons are considered as prototypical reactive intermediates and have attracted intensive interest. 5 Usually, NHCs use the normal carbene center (e.g. C2 of 1 0 in Scheme 1) to form h 1 complexes. 6 However, recent experimental and theoretical results show that abnormal carbenes with C5 as the active center (e.g. 1 in Scheme 1) have a stronger electron-donating ability and, accordingly, their complexes show better catalytic properties than the normal ones. 7,8 As a direct result, great efforts have been devoted to the exploration of abnormal carbene compounds. 9 In contrast, carbon-based Lewis acids are limited merely to trityl cations and some electron-poor allenes. 4 Recently, Bazan and coworkers reported that fullerenes such as C 60 and C 70 can behave as all-carbon Lewis acids to form the corresponding Lewis acid-base pairs with a normal NHC structure (1 0 ). 10 This work opens a new perspective on the research of carbon-based Lewis acids. Meanwhile, as a novel class of metal-carbon hybrid molecules, endohedral metallofullerenes (EMFs) feature electron transfer from the internal metallic species to the carbon cage, forming zwitterionic compounds. 11 Accordingly, it is of special interest to study whether the highly charged carbon cages of EMFs are willing to accept additional electrons to act as Lewis acids or not.
Herein, taking Sc 3 N@I h -C 80 as a representative, we show that EMFs also exhibit excellent Lewis acidity to form Lewis acidbase pairs with NHCs. Surprisingly, our unambiguous X-ray results reveal that the abnormal NHC 1 is bonded to Sc 3 N@I h -C 80 , instead of the normal one 1 0 (Scheme 1). More interestingly, a singly bonded [6,6,6]-adduct (2a) of Sc 3 N@I h -C 80 is formed during the reaction, which has never been observed or even predicted, in contrast to the commonly observed [5,6,6]-adduct (2b). Our theoretical results reveal that the regioselective formation of the unprecedented [6,6,6]-adduct with an abnormal carbene moiety (2a) is synergistically affected by the cage size of Sc 3 N@I h -C 80 and the electronic density distribution on the cage.

Results and discussion
In a typical reaction, an ortho-dichlorobenzene (ODCB) solution of Sc 3 N@I h -C 80 and an excess amount (ca. 50-fold) of 1,3-bis-(diisopropylphenyl)-imidazol-2-ylene (1) was heated to 90 C under an argon atmosphere (Scheme 1). The reaction progress was monitored via high performance liquid chromatography (HPLC). Aer the solution was heated for 12 hours, a new peak appeared at 18.3 min, which is ascribed to the adduct 2a as identied using mass spectrometry (Fig. 1). The reaction was terminated aer 24 hours, and 2a was isolated with preparative HPLC in $80% conversion yield based on consumed Sc 3 N@I h -C 80 . The matrix assisted laser desorption/ionization time-of-ight (MALDI-TOF) mass spectrum of 2a displays a single peak at m/z 1498.2, rmly conrming the successful attachment of the NHC moiety onto the fullerene cage (Fig. 1b).
The electronic conguration of 2a was investigated using UV-Vis-NIR spectroscopy in toluene (Fig. 2). Although the spectrum of 2a resembles that of pristine Sc 3 N@I h -C 80 in the wavelength range between 540 nm and 1100 nm, their curves at 350-540 nm differ signicantly from one another, conrming that the electronic structure of Sc 3 N@I h -C 80 has been altered by the modication.
The structure of 2a is unequivocally established via singlecrystal X-ray crystallography. The entire system is fully ordered, including the functionalized cage, the internal cluster and even the three CS 2 solvent molecules. 12 It is evident that a single bond is formed between the addend and the cage with a bond length of 1.515Å (C5-C6), conrming unambiguously the formation of a Lewis acid-base complex (Fig. 3a). 13,14 More surprisingly, the addition site on the cage of Sc 3 N@I h -C 80 involves a triple hexagon junction (THJ) which is generally less reactive than the carbon atoms of other kinds on a fullerene cage. Such an addition pattern has never been observed or even expected for Sc 3 N@I h -C 80 because previously reported singly bonded derivatives contained at least two substituents that are exclusively linked to the pentagon-hexagon-hexagon junction (PHHJ) carbon atoms unless the cage is severely functionalized. [15][16][17] Because of the substitution, the carbon atom at the site of addition (C6) is slightly pulled out from the cage sphere which causes a 'Y-shaped' displacement of the internal Sc 3 N cluster with the Sc 3 -N1 bond nearly collinear with the new bond C5-C6, whereas the Sc 3 N-plane is perpendicular to the N-heterocyclic ring of the addend (Fig. 3b).
Surprisingly, the NHC moiety is linked to the cage of Sc 3 N@I h -C 80 with its abnormal carbene center C5 instead of the normal site C2, which is completely different from the corresponding Lewis pairs of C 60 and C 70 . 10 The bond length of C4-C5 (1.367Å) falls into the range of a C]C double bond, con-rming the existence of imidazol-2-ylene. The lengths of the The unprecedented structure of 2a with an abnormal NHC moiety singly bonded to a THJ carbon atom is of great interest. First, we try to understand why a [6,6,6]-adduct (2a) is formed instead of the corresponding [5,6,6]-adduct (2b). It is wellknown that THJ carbons are less pyramidal and accordingly are less reactive than the carbon atoms of other kinds of fullerenes. 18 Indeed, our theoretical results suggest that the [5,6,6]adduct 2b, if formed, is 0.49 kcal mol À1 more stable than the [6,6,6]-adduct 2a (Fig. 4a), indicating that the preferential formation of 2a is not a thermodynamically controlled process. We then consider that the electron density distribution on the cage of Sc 3 N@I h -C 80 should be a critical factor. It is widely accepted that pentagons are the sites of the negative charges of highly charged fulleride species such as EMFs. 19 Accordingly, [5,6,6]-junction carbon atoms always accumulate more negative charges than THJ carbons do. As a direct result, NHCs as electron-rich Lewis bases tend to attack the [6,6,6]-junction carbon atoms which have lower electron densities, revealing the Lewis acidic property of Sc 3 N@I h -C 80 . In summary, the [6,6,6]-addition pattern of 2a is a consequence of the electron density distribution on the cage of Sc 3 N@I h -C 80 .
We then try to nd a reasonable explanation for the unexpected formation of the abnormal carbene structure of 2a. Usually NHCs use the normal carbene center (C2 in 1 0 , Scheme 1) to bind metals. However, abnormal NHC carbene species (1, Scheme 1) can stably exist and can even be isolated. 20 Several examples of abnormal carbene complexes have been reported, which show enhanced catalytic properties for the activation of unreactive bonds. 7,8 Furthermore, Dagorne and coworkers reported that a normal but sterically congested NHC-AlMe 3 Lewis acid-base pair can isomerize to its abnormal NHC-AlMe 3 species. 20 This result inspires us to speculate that the abnormal carbene structure of 2a is also caused by a steric effect. Our computational results showed that neither the normal [6,6,6]-adduct (2a 0 ) nor the normal [5,6,6]-adduct (2b 0 ) can exist as stable compounds: during the optimization processes the single bond connecting the normal NHC moiety and Sc 3 N@I h -C 80 is broken (Fig. 4b), which can be attributed to the steric hindrance between the congested diisopropylphenyl groups of the normal NHC (1 0 ) and the large cage of Sc 3 N@I h -C 80 .
Finally, we propose a plausible mechanism to rationalize the unexpected formation of 2a (Scheme 2). According to the literature, the normal carbene 1 0 , where C2 is the carbene center, can tautomerize into the abnormal one 1 with C5 as the active  This journal is © The Royal Society of Chemistry 2016 site. 21 Then, the tautomers (1 and 1 0 ) turn into the corresponding mesoionic compounds. 9 Since the mesoionic species of 1 0 can not form stable adducts (2a 0 and 2b 0 ) with Sc 3 N@I h -C 80 because of the high steric hindrance between the addend and the cage, only the abnormal carbene structure is possible. As discussed above, the electron-rich NHC 1 (or the corresponding mesoionic compound) tends to attack one of the THJ carbon atoms with low electron densities, forming the [6,6,6]-adduct 2a in a highly regioselective manner.

Conclusions
In summary, Sc 3 N@I h -C 80 is conrmed to be an excellent carbon-based Lewis acid although its cage is negatively charged, representing the rst example of EMFs that readily undergo Lewis acid-base complexation reactions with NHCs. The regioselective formation of the unusual singly bonded [6,6,6]adduct 2a is reasonably interpreted by analyzing the charge density distribution on the cage because the electron-rich NHC is prone to attack one of the THJ carbons with low electron densities. More interestingly, Sc 3 N@I h -C 80 here is found to selectively trap the rare abnormal NHC 1 as a consequence of the steric hindrance between the normal NHC moiety and Sc 3 N@I h -C 80 . Hence, we conclude that the regioselective and unprecedented formation of 2a is a synergistic effect of both the cage size and electron density distribution of Sc 3 N@I h -C 80 . This synthetic strategy can be easily extended to create various EMFbased Lewis acid-base pairs with different metallic cores and/or cage structures, which may show unique catalytic properties in organic synthesis, taking into account their "frustrated" characteristics.