Cationic 5-phosphonio-substituted N-heterocyclic carbenes †

2-Phosphanyl-substituted imidazolium salts 2-PR 2 (4,5-Cl-Im)[OTf] ( 9a,b [OTf]) (4,5-Cl-Im = 4,5-dichloro-1,3-bis(2,6-di-isopropylphenyl)-imidazolium) (a: R = Cy, b: R = Ph) are prepared from the reaction of R 2 PCl (R = Cy, Ph) with NHC 8 (4,5-dichloro-1,3-bis(2,6-di-isopropylphenyl)-imidazolin-2-ylidene) in the presence of Me 3 SiOTf. 5-Phospanyl-substituted imidazolium salts 5-PR 2 (2,4-Cl-Im)[OTf] ( 10a,b [OTf]) are obtained in quantitative yield when a slight excess of the NHC 8 is used. 5-Phosphonio-substituted imidazolium salts 5-PR 2 Me(2,4-Cl-Im)[OTf] 2 ( 14a,b [OTf] 2 ) and 5-PR 2 F(2,4-Cl-Im)[OTf] 2 ( 16a,b [OTf] 2 ) result from methylation reaction or oxidation of 10a,b [OTf] with XeF 2 and subsequent ﬂ uoride abstraction. According to our quantum chemical studies the Cl1 atom at the 2-position at the imidazolium ring of dication 14b 2+ carries a slightly positive charge and is therefore accessible for nucleophilic n) 35 + of which the gold complex 36 + is readily accessible via the reaction with AuCl(tht).


Introduction
The application of N-heterocyclic carbenes (NHCs) in phosphorus chemistry has led to some remarkable discoveries in recent years and is a growing field with considerable impact. The most general feature of NHCs is their tendency to react at the 2-position with electrophilic P III compounds, leading to the corresponding 2-phosphanyl-substituted imidazolium salts or to donor-acceptor complexes of the NHC and the respective P-centered moiety. 1,2 In contrast, only a few examples are known where the 4/5-position of NHCs can be selectively addressed to yield 4/5-phosphanyl-substituted NHCs or imidazolium salts. Reactions are reported involving inter alia phosphaalkenes 3 and chlorophosphanes. 4,5 In 2009 Gates and coworkers observed the unusual reaction of 1,3-di(mesityl)imidazolin-2-ylidene 1 with phosphaalkene MesPvCPh 2 to afford the first example of a neutral 4-phosphanyl-substituted NHC 2 (Scheme 1, top). 3 Shortly afterwards, Bertrand and coworkers observed the rearrangement reaction of 2-phosphanylsubstituted imidazolium salt 3[Cl] to the 4-substituted derivative 4 when treated with a base (e.g. KHMDS; Scheme 1, middle). 4 The neutral 4-phosphanyl-substituted NHCs 2 and 4 were used as ligands in transition metal chemistry to generate mono metallic, 6 homo-6,7 and hetero-7 bimetallic complexes. In 2013 our group reported on the reaction of P-centered imidazolium salt 5[OTf ] with NHC 6 leading to the cationic phosphoranide derivative 7 [OTf ] where the second imidazoliumyl-substituent is bonded via the 4-position to the P atom (Scheme 1, bottom). The proposed mechanism includes the formation of an abnormal carbene 8 followed by an intermolecular rearrangement, which we believe is related to Bertrands mechanism for the formation of 4. 4 Only very few examples of 4-, 4,5-bisphosphoryl- 9 and 4,5bis-phosphanyl-10 substituted imidazolium salts and 4-phosphanido-substituted NHC 11 are reported in the literature so far. The aforementioned compounds exhibit either one or two Lewis basic functionalities. However, so far there is no example of a cationic NHC featuring a phosphonium functionality at the 4/5-position, which should have a significant influence on the reactivity of the carbene.
One of the oxygen atoms of one triflate anion shows a close contact to the Cl1 atom that is well within the sum of the van der Waals radii (O4⋯Cl1 2.813(2) Å; r A(O) + r A(Cl) = 3.21 Å). 19 Also the almost linear C1-Cl1-O4 angle of 170.879(6)°is indicative for a strongly directional rather than purely electrostatic interaction, namely a halogen bonding. 20 Fig. 2 Time-dependent 31 P NMR spectra for the reaction of 9b[OTf ] with 0.3 eq. of NHC 8 (o-C 6 H 4 F 2 , C 6 D 6 -capillary, 300 K). The intermediately formed cation 12b + is indicated by red and blue dots, not identified intermediates by asterisks.
Scheme 3 Proposed mechanism for the formation of cations 10b + ; anions are omitted for clarity. This effect might be attributed to a slightly increased electrophilic character of the Cl1 atom caused by the high group electronegativity of dication 14b 2+ (vide infra). [20][21][22] The quantitative oxidation of 10a,b[OTf ] via the slow addition of a solution of XeF 2 in CH 2 Cl 2 affords the difluorophosphoranes 15a,b[OTf ] (isolated yield >80%; Scheme 4). Analytically pure compounds are obtained via precipitation with n-hexane. For both compounds the 31 P NMR spectra show the expected triplet resonance with a typical 1 J PF coupling due to the presence of two chemically equivalent fluorine atoms (15a + : δ(P) = −28.6 ppm, 1 J PF = 722 Hz; 15b + : δ(P) = -64.9 ppm, 1 J PF = 715 Hz). Single crystals suitable for structure investigation are obtained by slow diffusion of n-hexane into a saturated CH 2 Cl 2 solution of 15b[OTf ]. Cation 15b + shows a trigonal bipyramidal bonding environment at the P atom with the F atoms being in the axial positions displaying an almost linear F-P-F angle of 172.91(10)°and typical P-F bond lengths (P-F1 1.6523(19) Å, P-F2 1.6582(19) Å; Fig. 3).
In order to shed light on the reactivity of dications 14a,b 2+ and 16a,b 2+ we analyzed the Merz-Kollman (M-K) and the Mulliken (Mull) charge distribution of 14b 2+ which are shown in Fig. 4 (left). Moreover, the Molecular Electrostatic Potential (MEP) distribution of 14b 2+ was calculated and plotted onto the van der Waals surface were regions of high charge are blue and regions with lower charge red (Fig. 4, right). For this study the geometries and energies were calculated applying the density functional theory (DFT) model BP86 26 with the latest correction of dispersion (D3), 27 together with the def2-TZVP basis set. 28,29 Both methods confirm a significant positive charge of the Cl atoms (Cl1: +0.41e (M-K), +0.12e (Mull); Cl2:  +0.30e (M-K), +0.01e (Mull)) which are bonded to the imidazolium ring, whereas the Cl1 atom, bonded to the 2-position, is more positive. The MEP surface illustrates that the imidazolium ring has the highest charge, however, it is not accessible for a nucleophilic attack due to steric effects. In sharp contrast, the Cl1 atom is very exposed and presents a σ-holea well defined positively charged region on the extension of the C1-Cl1 bond. 20,30 Therefore, the most reactive site towards voluminous nucleophiles in dication 14b 2+ is indeed the Cl1 atom bonded at the 2-position.
Similarly, the reaction of 16a,b[OTf ] 2 with Ph 3 P leads to the quantitative formation of chlorophosphonium salt Ph 3 PCl [OTf ] (δ(P) = 65.5 ppm) 31  . 18b[OTf ] shows a slightly downfield shifted doublet resonance at δ(P) = 76.8 ppm ( 1 J PF = 996 Hz) in the 31 P NMR spectrum compared to the starting material 15[OTf ] 2 (δ(P) = 70.5 ppm). The confirmation of the carbene was given by the 13 C{ 1 H} NMR spectrum showing a resonance at δ(C) = 230.8 ppm, 16,32 which splits into a pseudo triplet ( 3 J CP = 5 Hz, 4 J CF = 5 Hz) due to the coupling to the phosphorus atom and the fluorine atom, respectively. Mechanistically, the formation of NHCs 17a,b + and 18a,b + proceeds via a S N 2(Cl) type reaction 33 which is initiated by the nucleophilic attack of R 3 P (R = Ph, Cy) on the σ-hole of the Cl1 atom bonded to the C2-position. This suggestion is supported by a detailed computational study considering a S N 2(Cl) type reaction. The calculations were performed using the high level ab initio method RI-MP2 34 with the def2-TZVP 28 basis set to obtain reliable reaction barriers (Fig. 6, left). 29 In initial calculations a minimalistic model was used considering PH 3 as nucleophile which reacts with 14b 2+ where the Dipp-substituents are replaced by H atoms. The reaction is initiated by the formation of a hypercoordinate complex I in which a P⋯Cl halogen bond 20 with a comparatively short bond distance of 3.151 Å is observed. This intermediate was found to be 9.2 kcal mol −1 lower in energy than the corresponding starting materials and is well organized for the subsequent S N 2(Cl) type reaction 33 as it presents an ideal directionality for the   Table 1.
nucleophilic attack. The transition state TS is only 9.4 kcal mol −1 higher in energy than the intermediate I, thus confirming that the formation of the carbene is energetically feasible. The resulting adduct P is 6 kcal mol −1 lower in energy than the intermediate I and in total 15.2 kcal mol −1 more stable than the starting materials. These findings were then transferred to the complete model with dicationic 14b 2+ and PPh 3 as nucleophile using the density functional theory methods BP86-D3/def2-TZVP 26-29 (Fig. 6, right). The hypercoordinate complex I′ with a P⋯Cl bond distance of 2.702 Å and the product P′ were computed. The obtained energy difference between I′ and P′ with a value of −9 kcal mol −1 is in good agreement with the high level ab initio MP2/def2-TZVP calculation of the minimalistic model.
As NHCs are extensively used in coordination chemistry of transition metals, the formation of a series of complexes was investigated.  16 The reaction of 14b[OTf ] 2 with Cy 3 P and one eq. AgOTf in THF leads to the formation of 22[OTf ] 3 which is a rare example of a tricationic bis-carbene silver complex. 35 The investigation of the NMR spectra of iso-  (Fig. 7). The Ag atom is in an almost linear arrangement between the two      (8) is also in line with the coordination to transition metals. 16 29 and subsequently investigated the IR stretching frequencies for the carbonyl ligands of the formed carbonyl complex (see Fig. S2.10 †). The average CO stretching frequency (ν av (CO) = 2040.3 cm −1 , TEP = 2051 cm −1 ) 18 indicate a weak donor ability of cationic NHC 17b[OTf ]. According to a recent work by Ganter and co-workers, the 1 J CH coupling constant in imidazolium salts correlates with the σ-donor strength of the corresponding carbene. 37 It was found that poor σ-donors reveal high coupling constants for the C-H bond, which can be explained by a higher s-orbital character of the corresponding C-H bond 38  25[OTf ] is extremely sensitive and decomposes readily in solution which prevents its isolation. In 2010 Bertrand and coworkers reported on the activation of the primary phosphane PhPH 2 using NHC 26 39 and isolated the insertion product of the oxidative addition 27 in high yield (Scheme 8I). 39 Only recently, Radius and co-workers reported on the dehydrogenative coupling of primary and secondary phosphanes utilizing the more electron deficient NHC 28 (Scheme 8II). 40 For the 1 to 2 reaction of 28 with Ph 2 PH an oxidative addition of the phosphane into the carbene moiety followed by a reductive elimination of the corresponding diphosphane and the 2,3dihydro-1H-imidazole 29 was assumed. 40 Similarly, the reaction of prim. and sec. phosphanes with the electron deficient cationic NHC 17b + was performed. The reaction of two equivalents Ph 2 PH with 17b + in 1,2-dichloroethane (DCE) at ambient temperature affords the quantitative formation of diphosphane Ph 4 P 2 after 12 h (Scheme 9, Scheme 9 P-P coupling reactions of R 2 PH (R = Ph, Cy, i Bu; top) and PhPH 2 (bottom) using 17b[OTf ] as hydrogen acceptor; (i) +2 eq. Ph 2 PH, DCE, r.t., 12 h; (ii) +2 eq. Cy 2 PH, CH 3 CN, r.t., 12 h; (iii) +2 eq. i Bu 2 PH, CH 3 CN, r.t., 10 h; (iv) +PhPH 2 , r.t., 10 h, product distribution estimated by integration of the 31 P NMR spectrum of the reaction mixture; (v) +CyPH 2 , r.t., 24 h, product distribution estimated by integration of the 31 P NMR spectrum of the isolated solid. Fig. S2.5 †). The 31 P NMR spectrum of the reaction mixture shows a singlet resonance at δ(P) = −16.3 ppm which can be attributed to Ph 4 P 2 40 and a singlet at δ(P) = 12.1 ppm, corresponding to the byproduct which is formed during the reaction. To our surprise, in depth NMR spectroscopic studies reveal dication 30 2+ as byproduct of this reaction and not the corresponding 2,3-dihydro-1H-imidazole. It was reported that aryl substituents at the phosphane are beneficial for the NHC mediated 40,41 or transition metal catalysed 42 dehydrocoupling reaction, since electron rich alkyl phosphanes gave either no, or a non-selective conversion. When alkyl phosphanes R 2 PH (R = Cy, i Bu) are reacted with 17b[OTf ] in a 2 to 1 stoichiometry in CH 3 CN at ambient temperature, a clean formation of the corresponding diphosphane R 4 P 2 (R = Cy, i Bu) is observed after 10 h reaction time. The reaction of 2 eq. Cy 2 PH with 17b[OTf ] in CH 3 CN leads to the formation of a colorless precipitate. The 31 P NMR spectrum of the isolated precipitate reveals a singlet resonance at δ(P) = −21.3 ppm illustrating a clean and quantitative formation of diphosphane Cy 4 P 2 (see Fig. S2.6 †). The 31 P NMR spectrum for the reaction of 2 eq. i Bu 2 PH with 17b[OTf ] shows a singlet at δ(P) = 13.5 ppm for 30 2+ and a singlet resonance at δ(P) = −52.4 ppm which is attributed to i Bu 4 P 2 . Small amounts of unreacted i Bu 2 PH give rise to a doublet resonance at δ(P) = −83.7 ppm due to a slight excess of the inserted phosphane in the reaction (see Fig. S2.7 †). No conversion is observed when 2 eq. of the more sterically encumbered t Bu 2 PH is reacted with 17b[OTf ], leading to the assumption that the dehydrogenative coupling reaction maybe limited by the steric demand but not necessarily by electronic effects of the corresponding substituents on the phosphane.
To support a possible reaction mechanism (Scheme 10), 5 eq. of Ph 2 PH and 17b[OTf ] were mixed together in DCE and the reaction mixture was investigated by means of 31 P NMR spectroscopy (Fig. 8). We assume that the first step of this reaction involves the nucleophilic attack of cation 17b + towards Ph 2 PH to give the hyper-coordinate intermediate 31 + . Related phosporanides were recently reported. 1g,5 This intermediate reacts with a second eq. of Ph 2 PH to 31H + , accompanied by the formation of Ph 2 PCl (δ(P) = 81.8 ppm). 13 Cation 31H + shows a doublet resonance due to proton coupling at δ(P) = 18.9 ppm ( 1 J PH = 477 Hz) and a singlet at δ(P) = 27.6 ppm for the tetra-coordinate phosphorus atom. Small amounts of cation 31 + are present in the spectrum as indicated by the observation of a singlet of low intensity at δ(P) = 26.4 ppm. The corresponding doublet for the penta-coordinate P-atom coincides with that of 31H + . Intermediate 31H + rearranges to 2,3-dihydro-1H-imidazole 32 + in accordance to the work by Bertrand, Röschenthaler and Radius. 1g,39,40 This cation readily reacts with the liberated Ph 2 PCl to dication 33 2+ which is indicated by the observation of two doublets at δ(P) = −23.4 ppm and δ(P) = 34.6 ( 1 J PP = -227 Hz) and a singlet resonance at δ(P) = 33.3 ppm for the phosphonium moiety in the backbone. In the last step, cation 33 2+ liberates Ph 4 P 2 accompanied by the formation of dication 30 2+ .
Scheme 10 Possible reaction mechanism for the P-P coupling reaction of 2 eq. R 2 PH with 17b + to R 2 P-PR 2 . Further reactivity studies of 17b[OTf ] were directed towards the synthesis of a cationic N-heterocyclic olefin (NHO). 45,46 Therefore we methylated in a first step the in situ formed cation 17b + obtained from 14b[OTf ] 2 and Cy 3 P with one equivalent of MeOTf to give dication 34 2+ (Scheme 11). Dication 34 2+ was isolated as triflate salt (isolated yield 91%) and investigated by means of multinuclear NMR spectroscopy and X-ray analysis (Fig. 9). The 1 H NMR spectrum of dissolved 34[OTf ] 2 in CD 2 Cl 2 reveals a doublet resonance at δ(H) = 2.91 ppm ( 2 J HP = 13.8 Hz) for the CH 3 -group which is bonded to the phosphorus atom whereas the CH 3 -group at the 2-position of the imidazolium ring gives a singlet resonance at δ(H) = 2.38 ppm. The 31 P NMR spectrum shows a quartet resonance at δ(P) = 15.6 ppm which is slightly upfield shifted compared to 14b 2+ (δ(P) = 16.9 ppm). Derivative 34[OTf ] 2 is readily deprotonated in a subsequent step by lithium diisopropylamide (LDA) in THF to give 35[OTf ] as yellow powder in excellent yield (93%). The 31 P NMR spectrum shows an upfield shifted quartet resonance at δ(P) = 9.6 ppm compared to dication 34 2+ (δ(P) = 15.6 ppm).
The doublet resonance for the CH 3 -group bound to the P atom is shifted to higher field (δ(H) = 1.83 ppm; 2 J HP = 13.6 Hz) compared to the corresponding CH 3 -group in 34 2+ (δ(H) = 2.91 ppm; 2 J HP = 13.8 Hz). The CH 2 -group at the 2-position of the imidazole ring gives rise to a doublet resonance at δ(H) = 2.54 ppm and a doublet of doublet resonance at δ(H) = 2.61 ppm due to the hindered rotation around the C1-CH 2 bond. Both signals exhibit a geminal coupling constant of 2 J HH = 3.7 Hz and the latter resonance shows an additional coupling to the P atom ( 5 J HP = 1.6 Hz) which is explained by the spatial arrangement of this proton (see Fig. S2.11 †). The C atom of the CH 2 -group resonates at δ(P) = 55.1 ppm which is in the typical range for an olefinic C atom. Single crystals suitable for X-ray crystallography are obtained by slow diffusion of Et 2 O into a saturated solution of 35[OTf ] in CH 3 CN at −35°C (Fig. 9). Compared to the molecular structure of 34 2+ the major differences are the elongated C1-N1/N2 bond distances (C1-  To proof the donor properties of cationic NHO 35 + , the triflate salt was reacted with one equivalent AuCl(tht) in THF at ambient temperature to afford the NHO gold complex 36 [OTf ] in good yield (71%, Scheme 12). The 31 P NMR spectrum of 36 [OTf ] reveals a slightly downfield shifted resonance at δ(P) = 9.6 ppm compared to the free ligand 35 + (δ(P) = 14.3 ppm). The 1 H NMR spectrum of 36 + shows a singlet resonance for the CH 2 -group at δ(H) = 2.36 ppm, thus the two protons of the CH 2 moiety become magnetically equal upon coordination to the transition metal due to the free rotation around the C1-CH 2 bond (see Fig. S2.11 †). The coordination of the gold chloride fragment to the CH 2 -group causes a pronounced high field shift in the 13 C NMR spectrum (δ(C) = 8.5 ppm) compared to cation 35 + (δ(C) = 55.1 ppm). Single crystals suitable for X-ray crystallography are obtained by slow diffusion of Et 2 O into a saturated solution of 36[OTf ] in CH 3 CN at −35°C (Fig. 9). The molecular structure of cation 36 + displays a tetra-coordinate bonding environment at the C4 atom with a C1-C4-Au bond angle of 116.2(2)°and an elongated C1-C4 bond length of 1.453(4) Å compared to that in 35 + (C1-C4 1.399(3) Å). This elongation is a result of the reduced π-bond character of the C1-C4 bond caused by the coordination of the gold chloride fragment.

Conclusions
In this contribution, we present a facile and high yielding syntheses of 2-phosphanyl-(9a,b[OTf ]) and 5-phosphanyl-(10a, b[OTf ]) substituted imidazolium salts from the reaction of the corresponding chlorophosphanes and NHC 8. Methylation or oxidation with XeF 2 and subsequent fluoride abstraction of these salts affords 5-phosphonio substituted imidazolium salts 14a,b[OTf ] 2 and 16a,b[OTf ] 2 in good to very good yields. Quantum chemical calculations revealed the Cl1 atom (σ-hole) the most reactive position towards bulky nucleophiles. Chlorenium abstraction is achieved by the addition of R 3 P (R = Ph, Cy) in a S N 2(Cl) type reaction to yield the first cationic 5-phosphonio-substituted NHCs 17a,b +  The isolation of the first NHC salts does impact the broad field of NHC chemistry since it allows the design of new charged systems (Chart 1). Thus, the opportunity of including a variety of different onio-substituents ( phosphanes, amines, pyridines 48 etc.) 49 allows for the introduction of additional cationic charges in 4/5-position. This should have a tremendous influence on the reactivity of the resulting carbenes which was already shown by a in situ formed pyridinio-substituted NHC derivative. 48 The introduction of a stereogenic center is feasible by the variation of the substituents at the phosphonium center, the substituents of the N atoms in the heterocycle, as well as the choice of counter-ions which makes the resulting systems interesting candidates for stereoselective transition metal or organo catalysis.