Structurally versatile phosphine and amine donors constructed from N-heterocyclic olefin units

A general strategy for the synthesis of hindered N- and P-based donors is presented whereby the strongly electron releasing N-heterocyclic olefin (NHO) unit, IPr[double bond, length as m-dash]CH-, (IPr[double bond, length as m-dash]CH- = [(HCNDipp)2C[double bond, length as m-dash]CH](-); Dipp = 3,6-(i)Pr2C6H2) is linked to terminally bound phosphine and amine donors. Preliminary coordination chemistry is presented involving phosphine (IPr[double bond, length as m-dash]CH)PR2 (R = (i)Pr and Ph) and amine (IPr[double bond, length as m-dash]CH)NMe2 ligands and the Lewis acids BH3 and AuCl. Interestingly, (IPr[double bond, length as m-dash]CH)NMe2 binds AuCl through an exocyclic olefin unit, while the softer phosphorus centers in (IPr[double bond, length as m-dash]CH)PR2 coordinate to yield Au-P linkages; thus the reported NHO-based ligands exhibit tunable binding modes to metals.


Introduction
Sterically encumbered phosphines and N-heterocyclic carbenes (NHCs) are effective ligands for supporting a variety of catalytic bond-forming processes, 1 and can stabilize highly reactive molecular entities via strong coordinative interactions. 2 Common traits between these two ligand classes are the presence of a strongly σ-donating atom, ease of synthesis, and a high level of structural tunability. A related ligand group that is attracting increasing attention of late are N-heterocyclic olefins (NHOs), 3 which contain considerable nucleophilic character due to the highly polarized nature of the exocyclic CvC double bond, allowing these species to be strong neutral 2-electron donors (Chart 1; left). Accordingly, NHOs are now being used to intercept reactive inorganic species, 4,5 as organo-catalysts for various polymerization strategies, 6 and as a component of pincer-type ligands. 7 In this paper, we present efficient routes to phosphine and amine donors that contain an NHO moiety [IPrvCH] − directly linked to P-and N-donor sites. As shown in Chart 2, there is a possibility of coordination through either the NHO (via carbon-ligation) or the terminal P/N atoms. Our current study was motivated in part by the prior work of Beller who demonstrated that imidazolium-alkylphosphines (Chart 1; right) when combined with Pd(II) sources and base, afforded active catalysts (in situ) for the hydroxylation of arylhalides, and for both C-N (Buchwald-Hartwig) and C-C (Sonogashira) coupling reactions. 8 Despite the possible formation of neutral NHO-linked phosphines (NHOPs; Chart 2; E = P) during Beller's catalytic processes, such ligands were not isolated, nor were any well-defined metal complexes with these ligands reported. As a result, we decided to explore this ligand class in more detail and consequently uncovered divergent coordination behavior towards AuCl, depending if hard amine-or soft-phosphine groups are appended to an NHO unit.
Scheme 1 In the reaction of IPrvCH 2 (1) and i Pr 2 PCl in a 1 : 1 ratio, we observe the formation of the imidazolium-alkylphosphine salt [IPr-CH 2 -P i Pr 2 ]Cl as well as the desired neutral NHO-appended phosphine 2.  Synthesis of the N-heterocyclic olefin amine (IPrvCH)NMe 2 4 In addition to preparing NHOPs, we wanted to see if a harder amine donor could be incorporated onto an NHO scaffold. The dimethylamino-substituted NHO, (IPrvCH)NMe 2 4, was prepared by combining two equivalents of the commercially available carbene IPr with one equivalent of Eschenmoser's salt [H 2 CvNMe 2 ]I 12 in toluene (eqn (2)). In this process, the first equivalent of IPr is believed to undergo a nucleophilic attack on the iminium moiety to form [IPr-CH 2 -NMe 2 ]I which is then subsequently deprotonated by a second equivalent of IPr to yield (IPrvCH)NMe 2 4 and the imidazolium by-product [IPrH]I (which can be recycled for the preparation of IPr) (eqn (2)). In a similar fashion as the syntheses of 2 and 3, the salt by-product [IPrH]I is much less soluble than the target ligand 4, thus separation could be achieved by filtering the reaction mixture. One drawback with this synthesis is that the crude samples of 4 occasionally contains ca. 5-10% of unreacted IPr (as determined by 1 H NMR), which is difficult to separate from (IPrvCH)NMe 2 4 due to their similar solubilities in common organic solvents. However, a successful way to remove the IPr contaminant involves adding a small amount of BPh 3 to form the known adduct IPr·BPh 3 , 13 which is much less soluble in hexanes than 4.

Coordination of the NHOPs 2 and 3 to BH 3 and AuCl
With the new NHOPs in hand, we first tested their reactivity with the Lewis acid source THF·BH 3 . When either (IPrvCH)-P i Pr 2 2 or (IPrvCH)PPh 2 3 was combined with THF·BH 3 in hexanes (eqn (3)), the reaction mixture went from yellow to colorless after 90 min at room temperature. After the volatiles were removed, the respective phosphine-borane adducts (IPrvCH) i Pr 2 P·BH 3 5 and (IPrvCH)Ph 2 P·BH 3 6 were isolated as colorless crystals in 52 and 56% yields after recrystallization from cold (−30°C) hexanes or toluene (slow evaporation), respectively. As expected, coordination of a BH 3 unit was evident by NMR spectroscopy, which showed broad 11 B NMR resonances at −42.0 and −35.8 ppm for 5 and 6, respectively, consistent with the presence of four-coordinate boron environments. In addition, considerable downfield shifts in the 31 P resonances were noted within the NHOPs upon BH 3 coordination: from −17.4 ppm in 2 to 21.9 ppm in (IPrv CH) i Pr 2 P·BH 3 5; from −31.4 ppm in 3 to 7.3 ppm in (IPrvCH)-Ph 2 P·BH 3 6. Such a substantial change in 31 P NMR chemical shift indicated the likely presence of BH 3 units bound to the phosphorus centers; this postulate was confirmed by performing single-crystal X-ray crystallography (5: Fig. 4; 6: Fig. 5).
As shown in Fig. 4, (IPrvCH) i Pr 2 P·BH 3 5 contains a P-bound borane residue with a P-B bond length of 1.9166(18) Å; for comparison, the dialkylphosphine-borane adduct t Bu 2 PH·BH 3 has a P-B bond length of 1.936(2) Å. 14 In the case of (IPrvCH) i Pr 2 P·BH 3 5, the P(1)-C(4) length [1.7504(14) Å] is contracted in comparison to the corresponding distance in the free phosphine (IPrvCH)P i Pr 2 2 [1.780(3) to 1.788(2) Å]. The After demonstrating the successful coordination of the small Lewis acid BH 3 to the NHOPs 2 and 3, we decided to expand our studies to include transition metals. Our initial explorations focused on the noble metals Pd and Pt since complexes bearing these elements in conjunction with bulky phosphines 15 and NHCs 16 are often used in metal-mediated crosscoupling reactions. Despite the presence of a potentially strongly coordinating terminal -P i Pr 2 unit in (IPrvCH)P i Pr 2 2, no discernable reaction was noted when excess 2 (2-3 equiv.) was combined with either Pd(PPh 3 ) 4 or Pt(PPh 3 ) 4 in hot C 6 D 6 (50°C) for 4 days (monitored by 31 P NMR spectroscopy). A similar lack of reactivity was found with the two coordinate Pt(0) complex Pt(P t Bu 3 ) 2 . Attempts to form a bis NHOP-PdCl 2 pre-catalyst 17 by treating PdCl 2 (NCPh) 2 with two equiv. of 2 in toluene, led to an immediate color change of the reaction mixture from yellow to dark red, however 31 P NMR analysis revealed the formation of six spectroscopically distinct products from which a single clean product could not be isolated.
Upon closer inspection of the structure of 7 ( Fig. 6) it is clear that the -P i Pr 2 unit is free to rotate with respect to the bulky IPrvCH-group. In the BH 3 adduct 5, the isopropropyl groups are rotated away from the IPr unit, while in (IPrvCH) P i Pr 2 ·PdCl(cinnamyl) 7 the phosphorus bound i Pr substituents are positioned toward one Dipp group, enabling the more hindered PdCl(cinnamyl) array to occupy a more open side of the NHOP ligand coordination sphere. Therefore despite the bulk of (IPrvCH)P i Pr 2 , there exists sufficient torsional flexibility to allow different coordination pockets to be formed (a useful property for catalysis when various intermediates need to be stabilized). The Pd-cinnamyl bonding interactions in 7 range from 2.113(6) Å to 2.261(5) Å with the longest Pd-C bond to C(53) positioned trans to the phosphine donor. In the NHC complex IPr·PdCl(cinnamyl), the related trans-positioned Pd-C bond length (with respect to the IPr donor) is 2.201(17) Å, 19 indicating that the ligand (IPrvCH)P i Pr 2 exerts a similar degree of trans-influence as IPr.
Given the difficulties faced in introducing an NHOP as a ligand to Pd and Pt centers, we decided the explore the coordi-  (7), B-P-C(61) 108.15 (7).  nation of this ligand class to gold(I) centers. Added motivation for this work stems from the rapidly growing use of Au(I) complexes in catalysis (e.g. in the hydroamination of alkynes). 20 A toluene solution of (IPrvCH)P i Pr 2 2 was added to a molar equivalent of Me 2 S·AuCl, and after stirring at room temperature for 2 h, (IPrvCH) i Pr 2 P·AuCl 8 was obtained as a pale yellow solid in an 85% yield after filtration of the reaction mixture and removal of the volatiles (eqn (4)); the resulting product was analytically pure as judged by satisfactory C, H and N analyses. Compound 8 was characterized by X-ray crystallography and the refined molecular structure is shown in Fig. 7. The metrical parameters within the IPrvCH-unit in 8 are similar to those in the BH 3 adduct (IPrvCH) i Pr 2 P·BH 3 5, with comparable P-C(4) and exocyclic C (1) 21 The corresponding diphenylphosphine-capped NHO complex (IPrvCH)PPh 2 ·AuCl 9 was prepared (98% yield) in a similar straightforward manner as 8, and exhibited the same overall geometry as in 8 (Fig. 8) with a slightly narrower P-Au-Cl angle of 168.72(4)°.

Dalton Transactions Paper
ð4Þ In an attempt to prepare a more reactive Au(I) complex for future catalytic trials, 20d the NHO-Au complex (IPrvCH)-Ph 2 P·AuCl 9 was treated with Na[BAr F 4 This reaction afforded a gummy orange precipitate from which a product of [BAr F 4 ] − anion activation [IPr-CH 2 -PPh 2 ·Au(3,5-(F 3 C) 2 C 6 H 3 )]BAr F 4 10 could be isolated and structurally characterized (eqn (5); Fig. 9). While the mechanism of this process is under investigation, protonation of the exocyclic olefin within the NHO unit occurred to yield an imidazolium-alkylphosphine ligand, 8 along with the removal of one Ar F unit from the generally unreactive weakly coordinating [BAr F 4 ] − anion. One possible source of the proton would be C-H activation of the backbone olefin within the IPr unit. 22 The generation of a highly electron deficient Au(I) center during the reaction process could facilitate the abstraction of Ar F from the [BAr F 4 ] − anion; although rare, related pro-   cesses have been noted with both phosphine and NHC-bound Au(I) centers. 23 The structure of 10 is shown in Fig. 9 and, as expected, a nearly linear coordination geometry exists at the Au(I) center [P-Au-C(71) angle = 174.82 (11) To further evaluate the donation abilities of the new phosphines, we targeted the preparation of NHOP·Rh(CO) 2 Cl complexes with the hope of obtaining informative ν(CO) IR data. 3d When the NHOPs 2 and 3 were each combined with 0.5 equiv. of [RhCl(CO) 2 ] 2 , three different Rh-P containing products were found, as evidenced by 31 P{ 1 H} NMR spectroscopy in the form of doublet resonances due to coupling to Rh (I = 1/2). Despite multiple attempts, we could not separate the products due to their similar solubilities in common organic solvents, and as such further investigations were not pursued.
Divergent coordination chemistry of (IPrvCH)NMe 2 4 As presented above, the NHOPs 2 and 3 exclusively bind to Lewis acidic units through the terminal phosphine residues. However in the corresponding amine-capped NHOs (such as 4) featuring hard N-donor sites, there exists a chance that olefin coordination could transpire with soft Lewis acids (Chart 1). Somewhat to our surprise, (IPrvCH)NMe 2 4 did not yield clean reactivity with THF·BH 3 , with multiple products identified by 11 B NMR spectroscopy. In contrast, an isolable 1 : 1 complex (IPrvCH)NMe 2 ·AuCl 11 formed as a yellow solid in 89% yield when 4 was combined with Me 2 S·AuCl in toluene (eqn (6)). The most drastic change in the 13 C{ 1 H} NMR spectra of the (IPrvCH)NMe 2 units was the upfield shift of the olefinic CHNMe 2 carbon from 89.0 ppm in free (IPrvCH)NMe 2 4 to a position of 58.4 ppm in 11; this latter spectroscopic signature suggested possible olefin coordination to gold in 11. Crystals of 11 were obtained for X-ray crystallographic analysis and despite the lower quality of the data, (IPrvCH)NMe 2 coordination through a C-Au linkage was confirmed with a distance of 2.044(15) Å; moreover a nearly linear geometry was present at gold [C(3)-Au-Cl angle = 177.6(4)°; see Fig. S32 in the ESI †]. Therefore one can see direct evidence for the two possible binding modes of NHO-supported amines and phosphines in this study (Chart 2).

Conclusion
We have reported efficient syntheses of neutral N-heterocyclic olefin-appended phosphines and amine donors, and present preliminary coordination behavior with the Lewis acids BH 3 and AuCl. Interestingly, modulation of the donor properties enables either NHO-based coordination (via an olefinic carbon atom) or standard phosphine binding modes to be adopted. As a result, we are exploring these coordinatively versatile ligands within the context of late metal-mediated catalysis.

General
All reactions were performed in either an inert atmosphere glove box (Innovative Technology, Inc.) or using Schlenk techniques. Solvents were dried using a Grubbs-type solvent purification system 24 11 B, and 11 B{ 1 H} NMR spectra were recorded on a Varian VNMRS-400 or Varian VNMRS-500 spectrometer and referenced externally to SiMe 4 , 85% H 3 PO 4 , or F 3 B·OEt 2 . Elemental analyses were performed by the Analytical and Instrumentation Laboratory at the University of Alberta. Melting points were measured in sealed glass capillaries under nitrogen using a MelTemp melting point apparatus and are uncorrected.

X-ray crystallography
Crystals for X-ray diffraction studies were removed from a vial and immediately coated with thin a layer of hydrocarbon oil (Paratone-N). A suitable crystal was then mounted on a glass fiber, and quickly placed in a low temperature stream of nitrogen on the X-ray diffractometer. All data (Tables 1 and 2) were collected using a Bruker APEX II CCD detector/D8 diffractometer using Mo Kα or Cu Kα radiation with the crystals cooled to −80°C or −100°C. The data was corrected for absorption through Gaussian integration from the indexing of the crystal faces. Crystal structures were solved using intrinsic phasing SHELXT 26 (2, 4, 5, 6, 9 and 11), direct methods (3), or Patterson/ structure expansion (7 and 8) 27 and refined using full-matrix least-squares on F 2 . The assignment of hydrogen atoms positions were based on the sp 2 or sp 3 hybridization of their attached carbon atoms, and were given thermal parameters 20% greater than those of their parent atoms.
Special refinement conditions (IPrvCH)P i Pr 2 ·BH 3 5. Attempts to refine peaks of residual electron density as disordered or partial-occupancy solvent hexane carbon atoms were unsuccessful. The data were cor-  rected for disordered electron density through use of the SQUEEZE procedure as implemented in PLATON. 28 A total solvent-accessible void volume of 1145 Å 3 with a total electron count of 212 (consistent with 4.24 molecules of solvent hexane, or ∼0.25 molecules per formula unit of 5) was found in the unit cell.
(IPrvCH)P i Pr 2 ·PdCl(cinnamyl) 7. The crystal used for data collection was found to display non-merohedral twinning. (IPrvCH)PPh 2 ·AuCl 9. Attempts to refine peaks of residual electron density as disordered or partial-occupancy solvent toluene or hexane carbon atoms were unsuccessful. The data were corrected for disordered electron density through use of the SQUEEZE procedure as implemented in PLATON. 28 A total solvent-accessible void volume of 517 Å 3 with a total electron count of 110 (consistent with 2 molecules of solvent toluene, or 0.5 molecules per formula unit of the Au complex) was found in the unit cell.

Synthetic details
Synthesis of (IPrvCH)P i Pr 2 2. i Pr 2 PCl (100 μL, 0.77 mmol) was added dropwise to IPrvCH 2 1 (0.508 g, 1.26 mmol) in 8 mL of THF. The resulting mixture was stirred for 20 h to give an orange suspension. The mixture was then filtered and the volatiles were removed from the filtrate to afford an orange solid that was extracted with 4 mL of hexanes and filtered again. Removal of the volatiles from the filtrate gave 2 as a light brown solid (0.267 g, 81%). Crystals suitable for X-ray crystallography were obtained by cooling (−30°C) a saturated solution of 2 in hexanes. 1  Synthesis of (IPrvCH)PPh 2 3. Ph 2 PCl (41.2 μL, 0.16 mmol) was added dropwise to a solution of IPrvCH 2 1 (0.150 g, 0.37 mmol) in 3 mL of THF. The resulting mixture was stirred overnight to give an orange suspension. The precipitate was allowed to settle and the mother liquor was isolated after filtration. The volatiles were removed from the mother liquor to afford (IPrvCH)PPh 2 3 as a brown solid (0.078 g, 83%). Crystals suitable for X-ray crystallography were obtained by cooling (−30°C) a saturated solution in hexanes. 1  Synthesis of IPrvCHNMe 2 4. A solution of IPr (0.481 g, 1.24 mmol) in 3 mL of toluene was added to finely ground [H 2 CvN(CH 3 ) 2 ]I (0.115 g, 0.62 mmol). The resulting mixture was stirred overnight to give a cloudy yellow reaction mixture. The mother liquor was isolated after filtration. The volatiles were then removed from the mother liquor to afford a yellow solid that was extracted with 2 mL of hexanes and filtered. Removal of the volatiles from the filtrate afforded 4 as a yellow solid (227 mg, 82%, product also contained 7% of unreacted IPr). Further purification can be performed by adding BPh 3 (ca. 2 mg) to 4 (0.050 g) in minimal amount of benzene (ca. 0.5 mL). The solution was stirred for 15 min and 2 mL of hexanes was added to yield a white precipitate. The mother liquor was isolated after filtration and the volatiles were removed from the filtrate to afford 4 (0.040 g) containing <1% of unreacted IPr. Crystals suitable for X-ray crystallography were obtained by cooling (−30°C) a saturated solution in hexanes. 1  Found: C, 79.04; H 9.43; N, 8.52. Despite repeated attempts, analyses were consistently low in the carbon content. See Fig. 7 and 8 in the ESI † for a copy of the NMR spectra of 4. Preparation of (IPrvCH)P i Pr 2 ·BH 3 5. 106 μL of THF·BH 3 (1.0 M solution in THF, 0.11 mmol) was added dropwise to a solution of IPrvCHP i Pr 2 2 (50 mg, 0.096 mmol) in 2 mL of hexanes. The reaction mixture was stirred for 1.5 h and then filtered. The volatiles were removed from the filtrate and the resulting solid was dissolved in approximately 0.5 mL of hexanes and cooled (−30°C) to afford (IPrvCH)P i Pr 2 ·BH 3 as a white microcrystalline solid (27 mg, 52%). Crystals suitable for X-ray crystallography were obtained by cooling (−30°C) a saturated solution in hexanes. 1 5 Hz, 12H, CH(CH 3 ) 2 ), 1.44 (broad septet, 2H, P(CH(CH 3 ) 2 ) 2 ), 1.14 (d, 3 J HH = 6.5 Hz, 12H, ArCH(CH 3 ) 2 ), 1.06 (dd, 3 J HH = 7.0 Hz, 3 J HP = added to solid Me 2 S·AuCl (40 mg, 0.14 mmol) to give a yellow solution. This reaction mixture was stirred at room temperature for 90 minutes and a small amount of metallic precipitate was observed. The mixture was filtered and the volatiles were then removed from the filtrate to afford (IPrvCH)PPh 2 ·AuCl 9 as a pale yellow solid (108 mg, 98%). Crystals suitable for X-ray crystallography were obtained by cooling (−30°C) a saturated solution in a 2 : 1 mixture of toluene/hexanes. 1 H NMR (400 MHz, C 6 D 6 ): δ 7.47-7.49 (m, 4H, PhH), 7.41 (t, 3 J HH = 8.0 Hz, 2H, ArH), 7.18 (d, 3 J HH = 8.0 Hz, 4H, ArH), 6.86-6.87 (m, 6H, PhH), 5.83 (s, 2H, N(CH) 2 N), 3.00 (septet, 3 J HH = 6.8 Hz, 4H, CH(CH 3 ) 2 ), 2.80 (d, 2 J HP = 6.4 Hz, 1H, CHPPh 2 ), 1.20 (d, 3 J HH = 6.8 Hz, 12H, CH(CH 3 ) 2 ), 1.08 (d, 3 J HH = 6.8 Hz, 12H, CH(CH 3 ) 2 ). (IPrvCH)-PPh 2 ·AuCl 9 (17 mg, 0.020 mmol) and Na[BAr F 4 ] (18 mg, 0.020 mmol) were combined in 2 mL of toluene and stirred at room temperature overnight. A pale orange solution formed along with a gummy orange precipitate. The mother liquor was decanted away and the precipitate was exposed to prolonged vacuum to yield an orange solid. This solid was then extracted with CH 2 Cl 2 (2 × 1 mL) and the combined extracts were filtered. The filtrate was then layered with 2 mL of hexanes before cooling to −30°C, leading to colorless crystals of 10 (19 mg). 1