Chelate Palladium(II) Complexes with Saturated N-Phosphanyl-N

Feb 15, 2016 - Chelate Palladium(II) Complexes with Saturated N-Phosphanyl-N-Heterocyclic Carbene Ligands: Synthesis and Catalysis. Anatoliy Marchenko...
1 downloads 3 Views 794KB Size
Download PDF
Article pubs.acs.org/Organometallics

Chelate Palladium(II) Complexes with Saturated N‑Phosphanyl-NHeterocyclic Carbene Ligands: Synthesis and Catalysis Anatoliy Marchenko,† Georgyi Koidan,† Anastasiia N. Hurieva,† Yurii Vlasenko,† Aleksandr Kostyuk,*,† and Andrea Biffis*,‡ †

Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanska 5, Kyiv-94, 02660, Ukraine Dipartimento di Scienze Chimiche, Università di Padova, Via Marzolo 1, 35131 Padova, Italy

‡

S Supporting Information *

ABSTRACT: N-Phosphanyl-N-heterocyclic carbenes (NHCPs) featuring a saturated imidazolin-2-ylidene or tetrahydropyrimid2-ylidene ring have been synthesized and characterized. The free carbenes exhibit good stability and can be stored in the solid state for months at ambient temperature without decomposition. Contrary to imidazoline-based NHCPs, which decompose by ring opening, N-phosphanyltetrahydropyrimid-2-ylidenes isomerize to 2-phosphanyl tetrahydropyrimidines upon heating. The free carbenes are capable of acting as chelating ligands toward palladium(II), forming very stable mononuclear complexes that have been structurally characterized. The catalytic potential of the complexes has been preliminarily assessed in cross-coupling reactions, most notably in the Suzuki coupling of aryl chlorides, where these complexes display promising activity, and in the copper- and amine-free Sonogashira coupling of aryl bromides.

■

INTRODUCTION Chelating bidentate ligands are ubiquitous in coordination chemistry, where the chelate effect greatly helps in stabilizing ligand−metal interactions.1 Particularly interesting are chelating bidentate ligands featuring coordinating moieties of different nature (heteroditopic ligands) since in their complexes the different nature of the groups interacting with the metal center allows tuning the stability of the complex, its stereochemical properties, and its reactivity at the coordination sites trans to the bidentate ligand; furthermore, if the strength of the interaction of the two coordinating groups with the metal center is widely different, one of the coordinating moieties can, under proper conditions, reversibly detach from the metal center, thus opening a coordination site on the metal and giving rise to the so-called “hemilabile” ligands.2 In the course of the past decade, several novel heteroditopic ligands have been prepared that feature N-heterocyclic carbenes (NHCs)3,4 as one of the coordinating moieties, as well as another coordinating group connected to the NHC through a linker, and their coordination chemistry has been thoroughly studied.5 In this context, we and others have recently developed N-phosphanyl-N-heterocyclic carbenes (NHCPs),6,7 as well as N-phosphanyl acyclic diaminocarbenes (ADCPs)8 as a novel class of bidentate ligands at carbon and phosphorus (Scheme 1). The coordination chemistry of these ligands has been, however, mainly investigated with group 11 metal centers, which typically form dinuclear complexes in which the NHCP acts as a bridging ligand. Much more scarce are the reports concerning complexes in which these molecules act as chelating ligands toward a single metal center,7a,e,8 and even fewer studies © XXXX American Chemical Society

Scheme 1. Typical Structures of NHCP and ADCP Ditopic Ligands

concern the properties of these complexes, such as their catalytic properties.7e,8 In this contribution, we would like to expand this chemistry, and in particular we report on the preparation of chelate palladium(II) complexes with novel, saturated N-phosphanyl NHCs, as well as on the catalytic performance of these complexes in C−C coupling reactions.

■

RESULTS AND DISCUSSION NHCPs 3a−c were synthesized following the procedure previously developed by us for N-phosphanylimidazolin-2ylidenes (Scheme 2).6c The parent N-aryl heterocycles 1a−c were treated with di(tert-butyl)chlorophosphane and sodium triflate in THF, affording the target salts 2a−c in high yield. The salts are crystalline solids, highly sensitive to hydrolysis. As expected, the quaternization of the nitrogen atom causes in all cases a significant downfield shift of the 1H and 13C NMR signals of the CH group in the 2-position, with respect to the parent heterocycle. Interestingly, while the 1H and 13C NMR Received: January 6, 2016

A

DOI: 10.1021/acs.organomet.5b01019 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics Scheme 2. Synthesis of the Saturated NHCP Ligands

spectra of all compounds display one set of signals, in the 31P NMR spectra of 2a,b two signals are recorded, at δ 140.2, 124.4 (7:1) and 139.3, 123.0 (10:1) ppm, respectively, which is probably due to hindered rotation about the P−N bond.9 Subsequent deprotonation by potassium hexamethyldisilazide allowed preparing in good yield the saturated NHCP ligands 3a−c. A bulky strong base has to be employed in the final deprotonation step; otherwise the base can behave as a nucleophile, attacking the heterocycle at the 2-position. This reactivity has been previously observed with N-phosphanylimidazolinium salts6c and characterizes also the N-phosphanyltetrahydropyrimidinium salts: this has been verified with substrate 2a, which upon reaction with methyllithium (nucleophilic attack by methyl) or tert-butyllithium (hydride abstraction from tert-butyl) yields the corresponding Nphosphanylhexahydropyrimidines, which can be isolated and characterized as the selenides 4a,b (Scheme 3).

Figure 1. Ball-and-stick view of 3b. Selected bond distances (Å) and bond angles (deg) are as follows: P(1)−N(1) 1.736(2), N(1)−C(1) 1.360(3), N(2)−C(1) 1.340(3), N(2)−C(2) 1.436(3); P(1)N(1)C(1) 122.0(1), N(1)C(1)N(2) 115.4(2), C(1)N(2)C(2) 118.6(2).

similarly to previously reported N-phosphanyl imidazol-, benzimidazol-, and triazol-2-ylidenes.6a,10,11 Scheme 4. Thermal Rearrangement of Carbenes 3a,b to Phosphanes 5a,b

Scheme 3. Alternative Reactions of Salt 2a with Lithium Alkyls

Group 16 elements (selenium in particular) usually react with NHCs affording the corresponding carbene−selenium adducts (selones),12 and previously investigated unsaturated NHCPs are no exception,6a,11 although ADCPs behave instead differently and can provide either the product of Se attack at the carbene carbon13 or, with more sterically encumbered carbenes, the product of Se attack at the phosphorus atom.9a In the case of saturated NHCPs, whereas five-membered 3c furnished the expected selone upon attack of Se to the carbene carbon,6c addition of Se to carbenes 3a,b led to a mixture of compounds, among which the expected selones were not detected. The reaction went to completion upon addition of 2 equiv of selenium, and products 6−8 (Scheme 5) could be separated

The novel free carbenes 3a,b were thoroughly characterized by NMR. The spectral features of the carbenes are comparable to those of the previously characterized, five-membered NHCP 3c,6c particularly concerning the 13C NMR signal of the carbene carbon and the 31P NMR signal of the phosphanyl moiety. Furthermore, the structure of compound 3b was confirmed by an X-ray study (Figure 1). It was found that there are two symmetrically independent molecules of 3b in the unit cell. The only difference between them is the location of the C(17) atom in the N(1)C(1)N(2)C(16−18) six-membered cycle. The N(1)C(1)N(2)C(16)C(18) fragment is planar within 0.032 Å in both molecules, and the atom C(17) is located above this plane in one molecule and under the plane in another one. The aromatic ring is orthogonal to the plane of the N(1)C(1)N(2)C(16)C(18) fragment; the dihedral angle between them is 86° for both independent molecules of 3b. N(1) and N(2) atoms have trigonal-planar bond orientation (sum of the bonds is 360.0(3)° and 360.0(4)°, respectively, for both molecules). Contrary to their five-membered congener 3c, which decomposes with ring opening upon heating,6c tetrahydropyrimid-2-ylidenes 3a,b cleanly undergo 1,2-P shift at 125 °C to give 2-phosphanyl tetrahydropyrimidines 5a,b (Scheme 4),

Scheme 5. Reaction of Carbenes 3a,b with Selenium

and isolated as individual compounds by silica gel chromatography, thus proving that Se reacted at both carbon and phosphorus atoms. We are currently evaluating whether this different reactivity is dictated by steric or electronic reasons. Carbenes 3a−c readily reacted with bis(benzonitrile)palladium(II) chloride to give chelating complexes 9a−c (Scheme 6). B

DOI: 10.1021/acs.organomet.5b01019 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics Scheme 6. Synthesis of the Palladium(II) Complexes 9a−c

Figure 3. Perspective view of the molecular structure of 9b, together with the atomic numbering scheme. Selected bond distances (Å) and angles (deg): Pd(1)−Cl(1) 2.3634(9), Pd(1)−Cl(2) 2.3509(8), Pd(1)−P(1) 2.2180(9), Pd(1)−C(1) 2.012(3), P(1)−N(1) 1.707(3), N(1)−C(1) 1.353(4), N(2)−C(1) 1.320(4), N(2)−C(2) 1.448(4); P(1)Pd(1)C(1) 68.07(9), Pd(1)P(1)N(1) 85.8(1), N(1)C(1)Pd(1) 104.9(2), P(1)N(1)C(1) 101.1(2), N(1)C(1)N(2) 119.4(3).

The complexes are light yellow solids that are well soluble in several polar organic solvents; they feature good stability and can be handled without special precautions both in the solid state and in solution. They were thoroughly characterized by 1 H, 13C, and 31P NMR spectroscopy, where they exhibited the expected resonances. With respect to the free carbenes, coordination to palladium(II) invariably results in a considerable upfield shift of the 13C NMR signal of the carbene carbon, as commonly observed in the formation of metal complexes of NHC ligands, including N-phosphanyl ones.6−8 In contrast, no significant shift of the phosphorus signal in the 31 P NMR spectrum is observed upon coordination of 3c to Pd to form 9c (δ 87.7 to 90.1 ppm), whereas a very remarkable upfield shift (δ ca. 112 to ca. 59 ppm) was recorded upon formation of 9a,b. The negligible variation of chemical shift recorded in the formation of 3c resembles the one previously reported with another five-membered NHCP ligand,7b whereas the large variations observed with the six-membered NHCPs are comparable to the ones previously observed with ADCP ligands.8 The structure of compounds 9a−c was determined by X-ray diffraction methods (Figures 2−4). All complexes display a

Figure 4. Perspective view of the molecular structure of 9c, together with the atomic numbering scheme. Selected bond distances (Å) and angles (deg): Pd(1)−Cl(1) 2.3532(9), Pd(1)−Cl(2) 2.3435(8), Pd(1)−P(1) 2.2363(8), Pd(1)−C(1) 1.981(3), P(1)−N(1) 1.708(3), N(1)−C(1) 1.357(4), N(2)−C(1) 1.307(4), N(2)−C(2) 1.435(4); P(1)Pd(1)C(1) 68.55(9), Pd(1)P(1)N(1) 84.53(9), N(1)C(1)Pd(1) 105.4(2), P(1)N(1)C(1) 101.5(2), N(1)C(1)N(2) 110.1(3).

electron donation to the metal center by the former.14 The most notable difference between the complexes with five- and six-membered NHCPs can be appreciated upon looking at the so-called “yaw distortion angle”,15 namely, the angle between the actual Pd−C bond axis and the “ideal” bond axis that passes through the carbene carbon and lies on the symmetry plane of the heterocyclic ring. This angle is easily estimated as the semidifference between the two Pd−C−N angles (if there is no significant distortion from planarity of the Pd−NCN moiety, as in the present case) and is much greater for 9c (19.51°) than for 9a,b (around 15°), indicating greater distortions in the structure of 9c, which should imply a lower stability of this complex. Finally, the Pd−C and Pd−P distances do not vary very significantly between the various complexes and are in the range of similar complexes reported in the literature.7b,8 We then set out to examine the potential of the Pd complexes as catalysts. Among the plethora of reactions that are known to be catalyzed by Pd species, we chose cross-couplings for these first studies, a reaction class for which very numerous catalytic systems based on Pd complexes with NHC ligands have been proposed and extensive literature surveys are available,16 thus facilitating a critical evaluation of the catalytic performance of the novel complexes.

Figure 2. Perspective view of the molecular structure of 9a, together with the atomic numbering scheme. Selected bond distances (Å) and angles (deg): Pd(1)−Cl(1) 2.361(2), Pd(1)−Cl(2) 2.369(2), Pd(1)− P(1) 2.211(2), Pd(1)−C(1) 2.008(6), P(1)−N(1) 1.710(5), N(1)− C(1) 1.368(9), N(2)−C(1) 1.320(9), N(2)−C(2) 1.429(8); P(1)Pd(1)C(1) 68.2(2), Pd(1)P(1)N(1) 86.1(2), N(1)C(1)Pd(1) 104.7(4), P(1)N(1)C(1) 100.2(4), N(1)C(1)N(2) 118.8(5).

distorted square planar coordination geometry with a very small CPdP angle (around 68°) imposed by the ligand geometry. The structure of the ligands is also strongly distorted compared to the free state; in particular, the CNP angle decreases from 122° to 101° in the case of 9b, whereas in the case of 9c the decrease is even more pronounced (from 126.9° to 101.55°). The NCN angle is as expected much wider for the complexes with the six-membered NHCPs (around 119°) than for the five-membered NHCP (110.17°), which should imply stronger C

DOI: 10.1021/acs.organomet.5b01019 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

chlorides at room temperature with down to 0.05 mol % catalyst9), are encouraging for further investigation on NHCP ligands and in particular compare favorably with those previously obtained by us with acyclic N-phosphanyl diaminocarbene ligands, where the lower stability of the Pd complexes was found to negatively affect the catalytic performance.8 We then turned our attention to another reaction, namely, the Hartwig−Buchwald coupling of aryl chlorides with substrates containing an N−H function to yield the corresponding N-aryl derivatives. This reaction is efficiently catalyzed by several palladium−NHC complexes,16 and chelating ligands bearing an NHC and a phosphane moiety have also been employed with success, enabling efficient catalysis with 1−2 mol % Pd already at room temperature.18 We took into consideration the reaction of 4-chloroacetophenone or 4-chlorotoluene with model substrates such as Nmethylaniline or morpholine under a variety of conditions by changing in particular solvent (ethanol, dimethoxyethane, 1,4dioxane, N,N-dimethylformamide), base (KOtBu, K2CO3), and temperature (room temperature to 80 °C). Unfortunately, in no case were we able to detect production of the expected Narylated product using complexes 9a−c as catalysts. We currently tend to attribute this lack of activity to the fact that NHCP palladium(II) complexes fail to efficiently effect the final reductive elimination to form the new C−N bond. This reaction step is rate-determining in Hartwig−Buchwald amination,19 and the NHCP ligands apparently fail to promote it, since the small bite angle furnishes smaller steric pressure toward reductive elimination and also disfavors formation of a chelate NHCP-palladium(0) complex, which would require an even broader bite angle. Finally, we evaluated our complexes as catalysts in the copper- and amine-free Sonogashira coupling of aryl halides and terminal alkynes to yield arylalkynes.20 Copper salts are generally required as cocatalysts for this reaction, since they react with the alkyne, forming intermediate Cu−alkynyl species, which then transmetalate to Pd; however, the use of copper species also makes the process air sensitive and promotes side reactions such as the Glaser−Hay coupling of the alkyne.21 Therefore, reaction protocols avoiding the use of copper cocatalysts, upon addition of a large excess of amine base or by other means, are currently being intensively investigated.20 In this connection, several NHC−palladium(II) complexes have recently been proposed as catalysts for copper-free Sonogashira reactions,22 although these complexes have not displayed up to now a very high reactivity, being able to efficiently convert only reactive aryl iodides and, to some extent, aryl bromides. Preliminary results obtained by employing complexes 9a−c as catalysts for this reaction are reported in Table 2. All complexes were found to be able to efficiently convert in 2 h an activated aryl bromide, such as 4-bromoacetophenone, and phenylacetylene into the Sonogashira product with good selectivity (Table 2, entries 1−4). The reaction could be efficiently run also at lower temperature, albeit by employing longer reaction times (Table 2, entry 2). In contrast, the situation was different with a deactivated aryl bromide such as 4-bromoanisole. In this case, complex 9a turned out to be inactive for the reaction after 2 h, whereas complexes 9b and 9c displayed a moderate activity (Table 2, entries 5−7); the catalytic performance was slightly better for the former complex, reaching 54% yield after 24 h (Table 2, entry 8). It is interesting to remark that the catalytic inactivity observed

We considered initially the Suzuki coupling of aryl bromides and chlorides with phenylboronic acid, a reaction for which NHC−Pd complexes are among the most efficient catalysts known to date.16 We started by working with an unactivated aryl bromide substrate such as 4-bromoanisole in order to optimize the reaction conditions and in particular the solvent and the temperature. We screened the most commonly employed media for this reaction and found that ethanol provided the best catalytic performance (Table 1, entries 1−3). Table 1. Suzuki Reactions Catalyzed by Complexes 9a−c

1 2 3 4 5c 6 7 8 9 10 11 12

R

X

cat

solventa

T (°C) /time (h)

yield (%)b

OCH3 OCH3 OCH3 OCH3 OCH3 COCH3 COCH3 CH3 OCH3 OCH3 OCH3 OCH3

Br Br Br Br Br Cl Cl Cl Cl Cl Cl Cl

9c 9c 9c 9a 9c 9c 9a 9a 9a 9a 9a 9b

DME DMF EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH EtOH

80/17 80/17 80/5 80/5 80/2 80/5 80/5 80/5 80/5 60/5 28/5 28/5

46 94 >99 >99 65 75 >99 >99 89 93 42 8

a

DME = dimethoxyethane; DMF = N,N-dimethylformamide. bYields determined by 1H NMR using 1,4-bis(trimethylsilyl)benzene as an internal standard. cReaction performed with 0.02 mol % catalyst.

In this solvent, the reaction proved to be very efficient with all employed catalysts and could be efficiently performed also with very low catalyst loadings. For example, the reaction using 0.02 mol % 9c allowed reaching a 65% yield within 2 h, with an average TOF of 1.6 × 103 h−1 (Table 1, entry 5). Subsequently, we turned our attention to more challenging substrates for the Suzuki reaction and selected some model aryl chlorides for this purpose. Indeed, while it is known that even simple Pd salts catalyze the Suzuki reaction of aryl iodides or bromides,17 the decreased reactivity of aryl chlorides makes the catalytic interference of Pd centers deriving from the potential decomposition of the complexes less likely and also allows a better discrimination between the catalytic activity of the various Pd complexes. Indeed, a significantly better performance in the conversion of 4-chloroacetophenone was recorded for complex 9a, bearing the six-membered NHCP, compared to complex 9c, with the five-membered one (Table 1, entries 6 and 7). This difference could be the consequence of the higher electron-donating capability of the six-membered NHC moiety compared to the five-membered one and/or of the increased stability of the complex due to lower strain of the chelating ligand in 9a compared to 9c. Complex 9a was a very efficient catalyst also in the conversion of less activated or even deactivated aryl chlorides, which allowed, in the case of deactivated 4-chloroanisole, performing the reaction in high yields at 60 °C and in moderate yields even at room temperature (Table 1, entries 10 and 11). In contrast, the more sterically encumbered complex 9b exhibited poor activity with 4-chloroanisole at room temperature (Table 1, entry 12), possibly due to steric reasons. These results, although not the best ever reported for NHC−palladium(II) complex catalysts (which currently enable high conversion of deactivated aryl D

DOI: 10.1021/acs.organomet.5b01019 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

diaminocarbene and a phosphane group. The lack of catalytic activity recorded in Hartwig−Buchwald couplings (and to some extent also in Sonogashira couplings) has been tentatively attributed to the fact that due to their small bite angle NHCPs as chelating ligands disfavor reductive elimination processes leading to palladium(0) species. Consequently, further investigation on the catalytic potential of these complexes will be extended to include also redox-neutral reactions, in which no reductive elimination processes are involved.

Table 2. Sonogashira Reactions Catalyzed by Complexes 9a−c

1 2 3 4 5 6 7 8 9 10 11

R

X

cat

T (°C) /time (h)

conversion (%)a

yield (%)b

COCH3 COCH3 COCH3 COCH3 OCH3 OCH3 OCH3 OCH3 OCH3 COCH3 COCH3

Br Br Br Br Br Br Br Br Br Cl Cl

9a 9a 9b 9c 9a 9b 9c 9b 9a 9b 9a

100/2 80/16 100/2 100/2 100/2 100/2 100/2 100/24 100/24 100/24 80/21

89 90 92 98 0 27 15 54 37 0 0

81 85 82 85 0 27 15 54 37 0 0

■

EXPERIMENTAL SECTION

All manipulations of air- and moisture-sensitive compounds were carried out using standard Schlenk techniques under an atmosphere of argon or dinitrogen. The reagents were purchased from Aldrich as high-purity products and generally used as received. All solvents were purified and dried by standard methods. Tetrahydropyrimidines 1a,b were prepared according to literature procedures.24 NMR spectra were recorded on a Bruker Avance spectrometer working at 500 MHz (500.13 MHz for 1H, 125.75 MHz for 13C, 202.43 MHz for 31P), 300 MHz (300.1 MHz for 1H, 75.5 MHz for 13C, 282.2 MHz for 19F, and 121.5 MHz for 31P), and 200 MHz (80.89 MHz for 31P); chemical shifts (δ) are reported in units of ppm relative to the residual solvent signals and to external 85% H3PO4 (for 31P). ESI-MS analyses were performed using an LCQ-Duo (Thermo-Finnigan) operating in positive ion mode. Instrumental parameters: capillary voltage 10 V; spray voltage 4.5 kV; capillary temperature 200 °C; mass scan range from 150 to 2000 amu; N2 was used as sheath gas; the He pressure inside the trap was kept constant. The pressure directly read by an ion gauge (in the absence of the N2 stream) was 1.33 × 10−5 Torr. Sample solutions were prepared by dissolving the compounds in acetonitrile. Sample solutions were directly infused into the ESI source by a syringe pump at an 8 μL/min flow rate. Elemental analyses were carried out with a Fisons EA 1108 CHNS-O apparatus or with a Carlo Erba analyzer. 3-(Di-tert-butylphosphanyl)-1-phenyl-3,4,5,6-tetrahydropyrimidin-1-ium Trifluoromethanesulfonate, 2a. To a solution of 1-phenyl-1,4,5,6-tetrahydropyrimidine (1a; 3.2 g, 20 mmol) and CF3SO3Na (3.9 g, 23 mmol) in THF (25 mL) was added di(tertbutyl)chlorophosphane (3.9 g, 22 mmol). Within 2 h the solvent was removed in vacuo, the solid residue was treated with CH2Cl2 (60 mL), the insoluble part was filtered off under argon and washed with CH2Cl2 (2 × 10 mL), and the filtrate was concentrated in vacuo. The residue was washed with Et2O (3 × 30 mL) to give the target salt as a white powder. Yield: 8.2 g (91%). Mp: 175−176 °C (THF). 1H NMR (CDCl3): δ = 1.33 (d, J = 13.5 Hz, 18H, CH3), 2.33 (m, 2H, CH2), 4.02 (br s, 2H, CH2), 4.10 (t, J = 5.4 Hz, 2H, CH2), 7.41−7.49 (m, 5H, CH), 8.22 (d, J = 6.3 Hz, 1H, CH). 13C NMR (CDCl3): δ = 19.3 (s, CH2), 28.8 (d, J = 16 Hz, CH3), 35.5 (d, J = 31 Hz, C), 44.9 (s, CH2), 46.8 (s, CH2), 120.5 (q, J = 321 Hz, CF3), 123.0 (s, CH), 129.2 (s, CH), 130.0 (s, CH), 141.1 (s, iC), 157.8 (d, J = 60 Hz, CH). 31P NMR (CDCl3): δ = 140.2, 124.4 (7:1). Anal. Calcd (%) for C19H30F3N2O3PS (454.5): C, 50.21; H, 6.65; N, 6.16. Found: C, 49.87; H, 6.41; N, 5.91. 3-(Di-tert-butylphosphanyl)-1-(2,4,6-trimethylphenyl)3,4,5,6-tetrahydropyrimidin-1-ium Trifluoromethanesulfonate 2b. The synthesis was performed following the same procedure employed for the preparation of 2a, starting from 2.8 g (14 mmol) of 1b. The reaction time was 1 h. Yield: 2.88 g (84%). 1H NMR (CDCl3): δ = 1.31 (d, J = 13.2 Hz, 18H, CH3), 2.19 (s, 6H, 2 CH3), 2.27 (s, 3H, CH3), 2.35 (m, 2H, CH2), 3.77 (m, 2H, CH2), 4.07 (br s, 2H, CH2), 6.95 (s, 2H, CH), 7.92 (d, J = 6.9 Hz, 1H, CH). 13C NMR (CDCl3): δ = 16.9 (CH), 19.4 (CH2), 20.6 (CH), 28.7 (d, J = 16 Hz, CH), 35.3 (d, J = 30 Hz, C), 45.0 (d, CH2, J = 6.3 Hz), 46.5 (CH2), 120.5 (q, J = 321 Hz, CF3), 129.8 (CH), 133.6 (C), 136.1 (C), 140.3 (C), 159.5 (d, J = 58 Hz, CH). 31P NMR (CDCl3): δ = 139.3, 123.0 (10:1). ESI-MS (positive ions, DMSO): m/z 347.26 [M]+ (5.9%); 363.0 [M + O]+ (51.5%); 203 [M − (tBu2P)]+ (28%). Anal. Calcd (%) for C22H36F3N2O3PS (496.58): C, 53.21; H, 7.31; N, 5.64. Found: C, 53.03; H, 7.43; N, 5.34.

a

Conversions based on the aryl halide. bConversions and yields determined by 1H NMR using 1,4-bis(trimethylsilyl)benzene as an internal standard.

with 9a and 4-bromoanisole appears to be due to the reluctance of the complex to undergo reduction under catalytic conditions to form the corresponding palladium(0) species from which the catalytic cycle starts with the oxidative addition of the aryl halide. Indeed, by prolonging the reaction time to 24 h a 37% yield in coupling product is recorded (Table 2, entry 9). Finally, all complexes proved completely inactive with an aryl chloride substrate such as 4-chloroacetophenone (Table 2, entries 10 and 11), which is a feature shared by all NHC-based Pd catalysts reported to date for this reaction. Summarizing these results, the reactivity of the complexes in these preliminary Sonogashira coupling tests seems at present comparable to or higher than that of previously reported mono- or di-NHC− palladium(II) complexes22 and markedly higher than that of previously reported Pd complexes with chelating ligands featuring a diaminocarbene and a phosphane group, which were moderately active only with aryl iodides.23 More investigations will be necessary in order to fine-tune the characteristics of the ligand for this peculiar application.

■

CONCLUSIONS In this work, we have disclosed novel N-phosphanyl-Nheterocyclic carbenes featuring a saturated tetrahydropyrimid2-ylidene ring. The carbenes exhibit good stability: they can be stored in the solid state for months at ambient temperature without decomposition and isomerize to the corresponding 2phosphanyl tetrahydropyrimidines only upon heating at 125 °C. The carbenes, together with a related imidazoline-based NHCP, act as chelating ligands toward palladium(II), forming in high yield complexes that are indefinitely stable in the solid state even without strict exclusion of air and moisture. The resulting palladium(II) complexes have been employed as precatalysts in cross-coupling reactions, most notably in Suzuki couplings of aryl chlorides, where the complexes display promising catalytic activity, in Hartwig−Buchwald couplings of aryl chlorides, in which the complexes are instead catalytically inactive, and finally in copper- and amine-free Sonogashira couplings of aryl bromides, where the catalytic performance of the complexes is comparable to that of previously reported NHC−palladium(II) species but superior to that of related palladium(II) complexes with chelating ligands featuring a E

DOI: 10.1021/acs.organomet.5b01019 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics 3-(Di-tert-butylphosphanyl)-1-phenyl- 3,4,5,6-tetrahydropyrimidin-2-ylidene, 3a. To a stirred solution of tetrahydropyrimidinium salt 2a (2.34 g, 5.15 mmol) in anhydrous and degassed THF (15 mL) cooled to −90 °C was added via syringe a 1 M solution of potassium hexamethyldisilazide (5.15 mL, 5.15 mmol) in THF. The reaction temperature was increased over 30 min to 17 °C. The solvent was removed in vacuo (15 Torr), and the residue was kept in vacuo until dry. Then pentane (20 mL) was added, the precipitate was filtered under argon and washed with pentane (3 × 10 mL), and the extracts were combined and concentrated in vacuo to 18 mL. The crystals formed at −18 °C were collected and dried in vacuo to give white crystals. Yield: 1.45 g (93%). 1H NMR (500 MHz, C6D6): δ = 1.35 (d, J = 12.0 Hz, 20 H, CH3+CH2), 2.80 (br s, 2H, CH2), 2.94 (br s, 2H, CH2), 6.95 (dd, J = 7.0 Hz, 1H, CH), 7.19 (dd, J = 6.5; 8.0 Hz, 2H, CH), 7.66 (d, J = 8.0 Hz, 2H, CH). 13C NMR (125.7 MHz, C6D6): δ = 21.2 (d, J = 10 Hz, CH2), 28.6 (d, J = 16.3 Hz, CH3), 34.9 (d, J = 26 Hz, C), 40.3 (s, CH2), 47.5 (d, J = 44 Hz, CH2), 118.1 (s, CH), 122.5 (s, CH), 127.9 (s, CH), 150.0 (s, C), 256.0 (s, C). 31P NMR (81 MHz, C6D6): δ = 113.5. Anal. Calcd (%) for C18H29N2P (304.42): C, 71.02; H, 9.60; N, 9.20. Found: C, 71.24; H, 9.71; N, 9.03. 3-(Di-tert-butylphosphanyl)-1-(2,4,6-trimethylphenyl)3,4,5,6-tetrahydropyrimidin-2-ylidene, 3b. The synthesis was performed following the same procedure employed for the preparation of 3b, starting from 1.5 g (3.0 mmol) of 2b. Yield: 690 mg (67%). Mp: 113−114 °C. 1H NMR (300 MHz, C6D6): δ = 1.37 (d, J = 11.7 Hz, 18H, CH3), 1.60 (m, 2H, CH2), 2.12 (s, 3H, CH3), 2.22 (s, 6H, CH3), 2.63 (t, J = 3.0 Hz, 2H, CH2), 3.04−3.07 (m, 2H, CH2), 6.76 (s, 2H, CH). 13C NMR (125.7 MHz, C6D6): δ = 17.3 (s, CH3), 20.2 (s, CH3), 21.8 (d, J = 10.0 Hz, CH2), 28.8 (d, J = 16.3 Hz, CH3), 34.8 (d, J = 25 Hz, C), 42.5 (s, CH2), 47.2 (d, J = 45 Hz, CH2), 128.7 (s, CH), 133.9 (s, C),134.8 (s, C), 144.9 (s, C), 254.1 (s, C). 31P NMR (81 MHz, C6D6): δ = 110.0. Anal. Calcd (%) for C21H35N2P (346.50): C, 72.79; H, 10.18; N, 8.08. Found: C, 72.91; H, 10.02; N, 8.19. 1-(Di-tert-butylphosphoroselenoyl)-2-methyl-3-phenylhexahydropyrimidine, 4a. To a stirred and cooled to −90 °C suspension of tetrahydropyrimidinium salt 2a (1.44 g, 3.2 mmol) in THF (10 mL) was added via a syringe a 1.6 N solution of methyllithium (2.0 mL, 3.2 mmol) in ether. The reaction mixture was stirred at −90 °C for 30 min. Then, the reaction temperature was slowly increased to +16 °C, and finely ground selenium (250 mg, 3.2 mmol) was added. The reaction mixture was stirred at 16 °C for 1 h. The solvents were removed in vacuo. The residue was extracted with hot hexane (3 × 20 mL); the extract was concentrated in vacuo to 18 mL. Upon cooling, the precipitate was formed, then collected and dried in vacuo to give 4a as white crystals. The mother liquor was concentrated, and residual matter was purified by chromatography on a SiO2 plate using CH2Cl2 as an eluent, Rf 0.6−1.0, and recrystallized. Combined yield: 0.99 g (79%). Mp: 144−145 °C (hexane). 1H NMR (CDCl3): δ = 1.23 (d, J = 6.5 Hz, 3H, CH3), 1.41 (d, J = 16.0 Hz, 9H, CH3), 1.49 (d, J = 16 Hz, 9H, CH3), 1.67 (d, J = 14.0 Hz, 1H, CH2), 2.03 (m, 1H, CH2), 3.21−3.28 (m, 1H, CH2), 3.41−3.43 (m, 1H, CH2), 3.49−3.55 (m, 1H, CH2), 3.65−3.68 (m, 1H, CH2), 6.63 (q, J = 6.0 Hz, 1H, CH), 6.79 (dd, J = 7.0; 7.5 Hz, 1H, CH), 6.96 (d, J = 8.0 Hz, 2H, CH), 7.24 (dd, J = 7.5; 8.5 Hz, 2H, CH). 13C NMR (CDCl3): δ = 11.3 (s, CH3), 25.0 (s, CH2), 27.9 (s, CH3), 30.0 (s, CH3), 39.4 (s, CH2), 41.0 (s, CH2), 41.2 (d, J = 43 Hz, C), 42.5 (d, J = 43 Hz, C), 68.9 (d, J = 6.3 Hz, CH), 115.8 (s, CH), 118.6 (s, CH), 128.8 (s, CH), 148.9 (s, iC). 31P NMR (CDCl3): δ = 111.5 (JPSe = 727 Hz). ESI-MS (positive ions, DMSO): m/z 401.2 [M + 2]+ (97.9%). Anal. Calcd (%) for C19H33N2PSe (399.42): C, 57.14; H, 8.33; N, 7.01; P, 7.75. Found: C, 57.02; H, 7.93; N, 7.22; P, 7.63. 1-(Di-tert-butylphosphoroselenoyl)-3-phenylhexahydropyrimidine, 4b. To a stirred and cooled to −100 °C suspension of tetrahydropyrimidinium salt 2a (1.60 g, 3.5 mmol) in THF (12 mL) was added dropwise over 3 min a 1.7 M solution of tert-butyllithium (2.1 mL, 3.5 mmol) in pentane. The reaction mixture was stirred at −60 °C for 2 h to give a clear solution. The reaction temperature was slowly increased to +16 °C, and finely ground selenium (280 mg, 3.5 mmol) was added. The reaction mixture was stirred at 16 °C for 2 h.

The solvents were removed in vacuo. The residue was extracted with hot hexane (3 × 20 mL); the extract was concentrated in vacuo to 15 mL. Upon cooling, a precipitate was formed, collected, and dried in vacuo to give 4b as white crystals. Yield: 1.09 g (86%, oil). Mp: 115− 117 °C (hexane). 1H NMR (300 MHz, C6D6): δ = 1.42 (d, J = 15.6 Hz, 18H, CH3), 1.77 (br m, 2H, CH2), 3.39 (t, J = 5.4 Hz, 2H, CH2), 3.66 (q, J = 5.4 Hz, 2H, CH2), 4.99 (d, J = 7.8 Hz, 2H, CH2), 6.83 (t, J = 7.2 Hz, 1H, CH), 7.08 (d, J = 8.1 Hz, 2H, CH), 7.26 (t, J = 8.4 Hz, 2H, CH). 13C NMR (125.7 MHz, C6D6): δ = 24.6 (s, CH2), 28.4 (s, CH3), 42.0 (d, J = 42 Hz, C), 48.2 (s, CH2), 49.4 (s, CH2), 69.3 (d, J = 4 Hz, CH2), 116.3 (s, CH), 119.3 (s, CH), 128.7 (s, CH), 148.4 (s, iC). 31P NMR (202.4 MHz, C6D6): δ = 110.9 (JPSe = 737 Hz). ESI-MS (positive ions, DMSO): m/z 387.0 [M + 2]+ (29.8%); 375.0 [M − CH2 + 4]+ (70.2%). Anal. Calcd (%) for C18H31N2PSe (385.39): C, 56.10; H, 8.11; N, 7.27; P, 8.04. Found: C, 55.78; H, 7.89; N, 7.56; P, 7.96. 2-(Di-tert-butylphosphanyl)-1-phenyl-1,4,5,6-tetrahydropyrimidine, 5a. A solution of 3a (164 mg, 0.54 mmol) in benzene-d6 (100 mg) was heated in the presence of tris(dimethylamino)phosphane selenide (26 mg, 0.11 mmol, 20 mol %) as catalyst at 125 °C for 45 min in a sealed tube. The solvent was removed in vacuo, and the solid residue was recrystallized from pentane. The crystals formed at −18 °C were collected and dried in vacuo to give 5a as a white powder. Yield: 153 mg (93%). Mp: 102−103 °C. 1H NMR (500 MHz, C6D6): δ = 1.32 (d, J = 11.5 Hz, 18H, CH3), 1.51 (m, 2H, CH2), 3.13 (t, J = 5.5 Hz, 2H, CH2), 3.46 (dd, J = 5.5 and 6.0 Hz, 2H, CH2), 6.90 (dd, J = 7.0 and 7.5 Hz, 1H, CH), 6.97 (d, J = 8.0 Hz, 2H, CH) 7.08 (dd, J = 7.5 and 8.0 Hz, 2H, CH). 13C NMR (125.7 MHz, C6D6): δ = 22.7 (s, CH2), 29.8 (d, J = 14 Hz, CH3), 32.95 (d, J = 24 Hz, C), 45.5 (s, CH2), 49.7 (d, J = 2.5 Hz, CH2), 124.3 (CH), 127.2 (CH), 128.0 (CH), 147.6 (d, J = 4 Hz, C), 160.7 (d, J = 18 Hz, CP). 31P NMR (81 MHz, C6D6): δ = 27.7. Anal. Calcd (%) for C18H29N2P (304.42): C, 71.02; H, 9.60; N, 9.20. Found: C, 70.78; H, 9.42, N, 9.15. 2-(Di-tert-butylphosphanyl)-1-(2,4,6-trimethylphenyl)1,4,5,6-tetrahydropyrimidine, 5b. A solution of 3b (150 mg, 0.4 mmol) in benzene-d6 (800 mg) was heated at 125 °C for 30 min in a sealed tube. The solvent was removed in vacuo, and the solid residue was recrystallized from pentane. The crystals formed at −18 °C were collected and dried in vacuo to give 5b as a white powder. Yield: 80 mg (53%). Mp: 98−99 °C. 1H NMR (300 MHz, C6D6): δ = 1.30 (d, J = 11.5 Hz, 18H, CH3), 1.59 (m, 2H, CH2), 2.06 (s, 3H, CH3), 2.23 (s, 6H, CH3), 2.93 (t, J = 5.0 Hz, 2H, CH2), 3.50 (t, J = 5.0 Hz, 2H, CH2), 6.69 (s, 2H, CH). 13C NMR (125.7 MHz, C6D6): δ = 18.9 (d, J = 5 Hz, CH3), 20.2 (s, CH3), 22.2 (s, CH2), 30.1 (d, J = 15 Hz, CH3), 32.8 (d, J = 24 Hz, C), 45.0 (s, CH2), 48.2 (d, J = 2.5 Hz, CH2), 128.8 (s, CH), 135.8 (s, C), 136.4 (d, J = 1.3 Hz, C), 140.4 (d, J = 2.5 Hz, C), 160.1 (d, J = 18 Hz, CP). 31P NMR (81 MHz, C6D6): δ = 34.5. Anal. Calcd (%) for C21H35N2P (346.50): C, 72.79; H, 10.18; N, 8.08. Found: C, 72.92; H, 10.02; N, 7.87. Reaction of Carbene 3a with Selenium. To a stirring suspension of salt 2a (2.27 g, 5.0 mmol) in THF (20 mL), cooled to −90 °C, was added a solution of lithium hexamethyldisilazide (880 mg, 5.2 mmol) in THF (10 mL) in one portion. The reaction mixture was kept stirring at −90 °C for 1 h; then the temperature was raised to −70 °C, and finely ground selenium (0.99 g, 12 mmol) was added. The reaction mixture was allowed to warm to 16 °C and kept stirring for 3 days. The reaction mixture was concentrated in vacuo. The residue was extracted with hexane (3 × 20 mL), and the solution was treated with activated charcoal and filtered. The solvents were evaporated, and the residue was separated by plate chromatography on silica gel using CH2Cl2 as an eluent. The crop Rf 0.8−1.0 gave a mixture of 6a and 8, the crop with Rf 0.7−0.8 gave 480 mg (1.25 mmol) of 7a (17%). The first crop was separated a second time using as an eluent CH2Cl2/hexane (2:1) to give 0.92 g (2 mmol) of 6a (27%), Rf 0.6−0.75, and 0.55 g (1.23 mmol) of 8 (33%), Rf 0.75−0.9. Di-tert-butyl(1-phenyl-1,4,5,6-tetrahydropyrimidin-2-ylselanyl)phosphaneselenide, 6a. Mp: 107−108 °C. 1H NMR (300 MHz, CDCl3): δ = 1.31 (d, J = 17.7 Hz, 18H, CH3), 2.03 (m, 2H, CH2), 3.61 (m, 2H, CH2), 3.76 (t, J = 6.0 Hz, 2H, CH2), 7.13−7.17 (m, 3H, CH), F

DOI: 10.1021/acs.organomet.5b01019 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics 7.24−7.30 (m, 2H, CH). 13C NMR (125.7 MHz, CDCl3): δ = 22.9 (s, CH2), 28.0 (s, CH3), 43.4 (d, J = 23 Hz, C), 47.9 (s, CH2), 50.7 (s, CH2), 125.1 (s, CH), 126.5 (s, CH), 128.1 (s, CH), 145.8 (s, iC), 146.9 (d, J = 6.3 Hz, CSe). 31P NMR (202 MHz, CDCl3): δ = 118.3 (JPSe = 364 and 751 Hz). ESI-MS (positive ions, DMSO): m/z 462.9 [M + 1]+ (100%). Anal. Calcd (%) for C18H29N2PSe2 (462.34): C, 46.76; H, 6.32; N, 6.06. Found: C, 46.29; H, 6.01; N, 6.97. 2-(Di-tert-butylphosphoroselenoyl)-1-phenyl-1,4,5,6-tetrahydropyrimidine, 7a. Mp: 126−127 °C. 1H NMR (300 MHz, CDCl3): δ = 1.45 (d, J = 15.6 Hz, 18H, CH3), 1.87 (m, 2H, CH2), 3.44 (t, J = 5.4 Hz, 2H, CH2), 3.74 (m, 2H, CH2), 7.05 (d, J = 7.2 Hz, 2H, CH), 7.19 (dd, J = 7.2; 7.5 Hz, 1H, CH), 7.25−7.30 (m, 2H, CH). 13C NMR (125.7 MHz, CDCl3): δ = 21.4 (s, CH2), 28.3 (s, CH3), 39.5 (d, J = 31 Hz, C), 46.3 (d, J = 14 Hz, CH2), 52.3 (d, J = 4 Hz, CH2), 125.2 (s, CH), 126.8 (s, CH), 128.2 (s, CH), 147.3 (s, iC), 154.4 (d, J = 101 Hz, CP). 31P NMR (202 MHz, CDCl3): δ = 73.0 ppm (JPSe = 723 Hz). ESI-MS (positive ions, DMSO): m/z 385.0 [M + 2]+ (100%). Anal. Calcd (%) for C18H29N2PSe (383.38): C, 56.39; H, 7.62; N, 7.31. Found: C, 55.93, H 7.38, N 7.45. Compound 8. Mp: 106−107 °C. 1H NMR (300 MHz, CDCl3): δ = 1.51 (d, J = 17.7 Hz, CH3). 13C NMR (125.7 MHz, CDCl3): δ = 28.4 (CH3), 43.7 (d, J = 19 Hz, C). 31P NMR (202 MHz, CDCl3): δ = 117.6 ppm (JPSe = 737 and 391 Hz). Reaction of Carbene 3b with Selenium. The same procedure was applied as for 3a. After evaporation of the solvents the residue was separated by plate chromatography on silica gel using as an eluent CH2Cl2. The crop Rf 0.85−1.0 gave a mixture of 6b and 8, and the crop with Rf 0.7−0.85 gave 107 mg (0.25 mmol) 7b (18%). The first crop was separated a second time using as an eluent CH2Cl2/hexane (2:1) to give 219 mg (0.43 mmol) of 6b (31%), Rf 0.75−0.9, and 38 mg (0.08 mmol) of 8 (12%), Rf 0.75−0.9. Di-tert-butyl(1-(2,4,6-trimethylphenyl)-1,4,5,6-tetrahydropyrimidin-2-ylselanyl)phosphaneselenide, 6b. Mp: 149−150 °C. 1H NMR (300 MHz, CDCl3): δ = 1.51 (d, J = 18.3 Hz, 18H, CH3), 2.01 (m, 2H, CH2), 2.26 (s, 3H, CH3), 2.28 (s, 6H, CH3), 3.33 (t, J = 5.4 Hz, 2H, CH2), 3.51 (t, J = 5.4 Hz, 2H, CH2), 6.85 (s, 2H, CH). 13C NMR (125.7 MHz, CDCl3): δ = 17.7 (s, CH3), 20.7 (s, CH3), 22.0 (s, CH2), 28.6 (s, CH3), 43.2 (d, J = 17.6 Hz, C), 46.2 (s, CH2), 48.3 (s, CH2), 129.2 (s, CH), 136.8 (s, C), 137.7 (s, C), 138.7 (s, C), 150.4 (d, J = 8.8 Hz, CSe). 31P NMR (202 MHz, CDCl3): δ = 111.9 (JPSe = 417 and 696 Hz). ESI-MS (positive ions, DMSO): m/z 505.0 [M + 1]+ (97%). Anal. Calcd (%) for C21H35N2PSe2 (504.42): C, 50.00; H, 6.99; N, 5.55. Found: C, 49.83; H, 6.59; N, 5.81. 2-(Di-tert-butylphosphoroselenoyl)-1-(2,4,6-trimethylphenyl)1,4,5,6-tetrahydropyrimidine, 7b. Mp: 178−181 °C. 1H NMR (300 MHz, CDCl3): δ = 1.44 (d, J = 15.9 Hz, 18H, CH3), 1.98 (m, 2H, CH2), 2.27 (s, 3H, CH3), 2.29 (s, 6H, CH3), 3.26 (t, J = 5.4 Hz, 2H, CH2), 3.67 (br s, 2H, CH2), 6.81 (s, 2H, CH). 13C NMR (125.7 MHz, CDCl3): δ = 18.8 (s, CH3), 20.6 (s, CH3), 22.4 (s, CH2), 28.9 (s, CH3), 40.7 (d, J = 33 Hz, C), 44.9 (d, J = 15 Hz, CH2), 51.2 (d, J = 4 Hz, CH2), 128.7 (s, CH), 135.9 (s, C), 136.4 (s, C), 140.1 (s, C), 150.9 (d, J = 102 Hz, CP). 31P NMR (202 MHz, CDCl3): δ = 71.5 ppm (JPSe = 716 Hz). ESI-MS (positive ions, DMSO): m/z 427.0 [M + 2]+ (99%). Anal. Calcd (%) for C21H35N2PSe (425.46): C, 59.29; H, 8.29; N, 6.58. Found: C, 58.89; H, 7.88; N, 6.96. Palladium Complex 9a. Carbene 3a was freshly prepared from 2a (2.31 g, 5.1 mmol) and a 1 M solution of potassium hexamethyldisilazide (5 mL, 5.1 mmol) as outlined above. The resulting pentane solution of the carbene was evaporated to dryness, and the residual solid was dissolved in THF (25 mL). Bis(benzonitrile)palladium(II) chloride (1.7 g, 2.4 mmol) was added, and the mixture was stirred at 20 °C for 15 h and then heated at 90 °C for 5 min. The precipitate was filtered off, washed with THF (2 × 15 mL), and dried in vacuo. The solid was recrystallized from acetonitrile (25 mL) to give 9a as yellow crystals. Yield: 0.83 g (71%). Mp: 300 °C (dec). 1H NMR (400 MHz, DMSO-d6): δ = 1.62 (d, JPH = 16.8 Hz, 18H, tBu), 2.17 (br s, 2H, CH2), 3.55 (br s, 2H, CH2), 3.72 (br s, 2H, CH2), 7.27−7.32 (m, 5H, CH). 13C NMR (75.5 MHz, DMSO-d6): δ = 20.4 (CH2), 28.4 (d, J = 5 Hz, CH3), 44.0 (s, CH2), 51.7 (s, CH2), 126.6 (s, CH), 127.8 (s, CH), 128.7 (s, CH), 144.8 (s, C), 189.5 (s,

C). 31P NMR (81 MHz, DMSO-d6): δ = 59.5. Anal. Calcd (%) for C18H29Cl2N2PPd (481.73): C, 44.88; H, 6.07; N, 5.82. Found: C, 44.51; H, 5.71; N, 5.69. Palladium Complex 9b. To a stirred solution of salt 2b (1.34 g, 2.7 mmol) in THF (15 mL), cooled to −90 °C, was added a solution of lithium hexamethyldisilazide (460 mg, 2.7 mmol) in THF in one portion. The reaction mixture was allowed to warm to 20 °C, then cooled to −70 °C, and a solution of bis(benzonitrile)palladium(II) chloride (960 mg, 2.5 mmol) in THF (20 mL) was added. After 15 h at 20 °C a very fine-grained precipitate was filtered off, washed with THF (2 × 20 mL), and dried in vacuo. The solid was extracted with dichloromethane (3 × 15 mL); undissolved solid was filtered off and recrystallized from acetonitrile. Dichloromethane was evaporated in vacuo. The residual solid was combined with the crystals that were collected from acetonitrile to give 9b as a yellow solid. Yield: 0.77 g (58%). Mp: 300 °C (dec). 1H NMR (500 MHz, DMSO-d6): δ = 1.59 (d, J = 17.0 Hz, 18H, tBu), 2.13 (br s, 2H, CH2), 2.17 (s, 6H, Me), 2.22 (s, 3H, Me), 3.41 (br s, 2H, CH2), 3.61 (br s, 2H, CH2), 6.83 (s, 2H, CH). 13C NMR (125.7 MHz, DMSO-d6): δ = 17.3 (s, CH3), 20.4 (s, CH2), 20.7 (s, CH3), 28.2 (s, CH3), 43.9 (s, CH2), 49.8 (s, CH2), 128.8 (s, CH), 133.5 (s, C), 186.5 (s, C). 31P NMR (81 MHz, DMSOd6): δ = 58.0. Anal. Calcd (%) for C21H35Cl2N2PPd (523.81): C, 48.15; H, 6.74; N, 5.35. Found: C, 47.71; H, 6.49; N, 5.51. Palladium Complex 9c. To a stirred solution of salt 2c (1.32 g, 2.7 mmol) in THF (15 mL), cooled to −40 °C, was added a solution of lithium hexamethyldisilazide (0.46 g, 2.7 mmol). The reaction mixture was allowed to warm to 20 °C, then cooled to 0 °C, and a solution of bis(benzonitrile)palladium(II) chloride (2.7 mmol) in THF (10 mL) was added. After 15 h at 20 °C a very fine-grained precipitate settled. THF was evaporated to dryness, and the residue was washed with 3 × 10 mL of diethyl ether. The solid was dried and then dissolved in methylene chloride (15 mL). Insoluble LiOTf was filtered and washed with methylene chloride (2 × 5 mL). The volume of methylene chloride was reduced to one-fifth, and the solution was left in a freezer at −10 °C to give 9c as yellow crystals.Yield: 0.77 g (57%). Mp: 250 °C (dec). 1H NMR (300 MHz, DMSO-d6): δ = 1.53 (d, JP−H = 17.1 Hz, 18H, tBu), 2.16 (s, 6H, Me), 2.24 (s, 3H, Me), 3.88 (t, J = 9.3 Hz, 2H, CH2), 4.15 (t, J = 9.9 Hz, 2H, CH2), 6.89 (s, 2H, CHAr). 13C NMR (125.7 MHz, DMSO-d6): δ = 17.4 (s, CH3), 20.6 (s, CH3), 27.7 (d, JC−P = 4 Hz, CH3), 48.7 (d, JC−P = 6 Hz, CH2), 52.4 (d, J = 3 Hz, CH2), 128.6 (s, CH), 132.9 (s, C), 134.6 (s, C), 137.5 (s, C), 165.8 (s, C). 31P NMR (81 MHz, DMSO-d6): δ = 90.1. Anal. Calcd (%) for C20H33Cl2N2PPd (509.78): C, 47.12; H, 6.52; N, 5.50. Found: C, 46.76; H, 6.28; N, 5.71. X-ray Crystal Structure Determination of Compounds 3b and 9a−c. All crystallographic measurements were performed at 173(1) K (for 3b, 9a, 9c) and 123(1) K (for 9b) on a Bruker Smart Apex II diffractometer (Mo Kα) operating in the ω and φ scan mode. Data were corrected for Lorentz and polarization effects. The SADABS procedure absorption correction was applied. The structures were solved by direct methods and refined by the full-matrix least-squares technique in the anisotropic approximation using the SHELXS97 and SHELXL97 programs25,26 and CRYSTALS program package.27 In the refinement the Chebychev weighting scheme28 was used. All hydrogen atoms were located in the difference Fourier maps and refined with fixed positional and thermal parameters. CCDC 1437123 (3b), 1437124 (9a), 1437122 (9b), and 1437233 (9c) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/data_request/cif. Full crystallographic details are also displayed in Table S1 in the Supporting Information. Catalytic Tests: Suzuki Reaction. Typical procedure: In a Schlenk tube equipped with a magnetic stirring bar were placed under an inert atmosphere 81 mg (0.66 mmol) of phenylboronic acid, 167 mg (1.2 mmol) of anhydrous K2CO3, and 6 μmol (1 mol %) of catalyst. The tube was degassed and put under an inert atmosphere. A 0.600 mmol amount of aryl halide and 5 mL of dry solvent were subsequently added. The flask was immediately placed in an oil bath preheated at the reaction temperature, and the reaction mixture was G

DOI: 10.1021/acs.organomet.5b01019 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

Danopoulos, A. A. Coord. Chem. Rev. 2007, 251, 610−641. (k) Peris, E.; Crabtree, R. H. Coord. Chem. Rev. 2004, 248, 2239− 2246. (6) (a) Marchenko, A. P.; Koidan, H. N.; Zarudnitskii, E. V.; Hurieva, A. N.; Kirilchuk, A. A.; Yurchenko, A. A.; Biffis, A.; Kostyuk, A. N. Organometallics 2012, 31, 8257−8264. (b) Marchenko, A. P.; Koidan, H. N.; Hurieva, A. N.; Gutov, O. V.; Kostyuk, A. N.; Tubaro, C.; Lollo, S.; Lanza, A.; Nestola, F.; Biffis, A. Organometallics 2013, 32, 718−721. (c) Marchenko, A.; Koidan, H.; Hurieva, A.; Vlasenko, Y.; Kostyuk, A.; Tubaro, C.; Lenarda, A.; Biffis, A.; Graiff, C. J. Organomet. Chem. 2014, 771, 14−23. (7) (a) Kühnel, E.; Shishkov, I. V.; Rominger, F.; Oeser, T.; Hofmann, P. Organometallics 2012, 31, 8000−8011. (b) Nägele, P.; Herrlich (neé Blumbach), U.; Rominger, F.; Hofmann, P. Organometallics 2013, 32, 181−191. (c) Ai, P.; Danopoulos, A. A.; Braunstein, P.; Monakhov, K. Y. Chem. Commun. 2014, 50, 103−105. (d) Brown, C. C.; Plessow, P. N.; Rominger, F.; Limbach, M.; Hofmann, P. Organometallics 2014, 33, 6754−6759. (e) Ai, P.; Danopoulos, A. A.; Braunstein, P. Inorg. Chem. 2015, 54, 3722−3724. (f) Ai, P.; Danopoulos, A. A.; Braunstein, P. Organometallics 2015, 34, 4109− 4116. (8) Marchenko, A.; Koidan, H.; Hurieva, A.; Vlasenko, Y.; Kostyuk, A.; Biffis, A. Dalton Trans. 2016, 45, 1967−1975. (9) (a) Marchenko, A.; Koidan, G.; Hurieva, A.; Kurpiieva, O.; Vlasenko, Y.; Rozhenko, A. B.; Kostyuk, A. Eur. J. Inorg. Chem. 2014, 2014, 3259−3270. (b) Aluri, B. R.; Burck, S.; Gudat, D.; Niemeyer, M.; Holloczki, O.; Nyulaszi, L.; Jones, P. G.; Heinicke, J. Chem. - Eur. J. 2009, 15, 12263−12272. (10) (a) Marchenko, A. P.; Koidan, H. N.; Huryeva, A. N.; Zarudnitskii, E. V.; Yurchenko, A. A.; Kostyuk, A. N. J. Org. Chem. 2010, 75, 7141−7145. (11) Marchenko, A. P.; Koidan, H. N.; Hurieva, A. N.; Pervak, I. I.; Shishkina, S. V.; Shishkin, O. V.; Kostyuk, A. N. Eur. J. Org. Chem. 2012, 2012, 4018−4033. (12) Bourissou, D.; Guerret, O.; Gabbaı, F. P.; Bertrand, G. Chem. Rev. 2000, 100, 39−91. (13) Marchenko, A.; Koidan, G.; Hurieva, A.; Savateev, A.; Kostyuk, A. Tetrahedron Lett. 2013, 54, 5671−5673. (14) Nelson, D. J.; Nolan, S. P. Chem. Soc. Rev. 2013, 42, 6723−6753. (15) Leung, C. H.; Incarvito, C. D.; Crabtree, R. H. Organometallics 2006, 25, 6099−6107. (16) (a) Marion, N.; Nolan, S. P. Acc. Chem. Res. 2008, 41, 1440. (b) Fortman, G. C.; Nolan, S. P. Chem. Soc. Rev. 2011, 10, 5151−5169. (c) Valente, C.; Calimsiz, S.; Hoi, K. H.; Mallick, D.; Sayah, M.; Organ, M. G. Angew. Chem., Int. Ed. 2012, 51, 3314−3332. (d) Ni, C.; Shen, A.; Cao, Y. C.; Ye, X. F. Youji Huaxue 2014, 34, 278−291. (17) Alimardanov, A.; Schmieder-van de Vondervoort, L.; de Vries, A. H. M.; de Vries, J. G. Adv. Synth. Catal. 2004, 346, 1812−1817. (18) Wheaton, C. A.; Bow, J.-P. J.; Stradiotto, M. Organometallics 2013, 32, 6148−6161. (19) Hartwig, J. F. Nature 2008, 455, 314−322. (20) Chinchilla, R.; Najera, C. Chem. Rev. 2007, 107, 874−922. (21) (a) Siemsen, P.; Livingston, R. C.; Diederich, F. Angew. Chem., Int. Ed. 2000, 39, 2632−2657. (b) Hay, A. S. J. Org. Chem. 1962, 27, 3320−3321. (22) (a) Batey, R. A.; Shen, M.; Lough, J. Org. Lett. 2002, 4, 1411− 1414. (b) Ray, L.; Barman, S.; Shaikh, M. M.; Ghosh, P. Chem. - Eur. J. 2008, 14, 6646−6655. (c) Luo, F.-T.; Lo, H.-K. J. Organomet. Chem. 2011, 696, 1262−1265. (e) Huynh, H. V.; Lee, C. S. Dalton Trans. 2013, 42, 6803−6809. (f) Yang, L.; Li, Y.; Chen, Q.; Du, Y.; Cao, C.; Shi, Y.; Pang, G. Tetrahedron 2013, 69, 5178−5184. (g) Biffis, A.; Cipani, M.; Bressan, E.; Tubaro, C.; Graiff, C.; Venzo, A. Organometallics 2014, 33, 2182−2188. (h) Lu, H.; Wang, L.; Yang, F.; Wu, R.; Shen, W. RSC Adv. 2014, 4, 30447−30452. (23) Eberhard, M. R.; van Vliet, B.; Duran Pachon, L.; Rothenberg, G.; Eastham, G.; Kooijman, H.; Speck, A. L.; Elsevier, C. J. Eur. J. Inorg. Chem. 2009, 2009, 1313−1316.

vigorously stirred for 5 h. A 14 mg (0.063 mmol) amount of 1,4bis(trimethylsilyl)benzene as an internal standard was then added. The mixture was evaporated to dryness and taken up in CDCl3. Yields were determined by 1H NMR. Catalytic Tests: Sonogashira Reaction. Typical procedure: In a Schlenk tube equipped with a magnetic stirring bar were placed under an inert atmosphere 0.600 mmol of aryl halide, 167 mg (1.2 mmol) of anhydrous K2CO3, and 6 μmol (1 mol %) of catalyst. The tube was degassed and put under an inert atmosphere. A 10 mL amount of dry DMF was subsequently added, followed by 132 μL (1.2 mmol) of phenylacetylene The flask was immediately placed in an oil bath preheated at 100 °C, and the reaction mixture was vigorously stirred for 2 h. The reaction mixture was then partitioned between 30 mL of water and 20 mL of diethyl ether, and the organic layer was further washed with 2 × 20 mL of water and dried over MgSO4. A 14 mg (0.063 mmol) amount of 1,4-bis(trimethylsilyl)benzene as an internal standard was then added, after which the mixture was evaporated to dryness and taken up in CDCl3. Yields were determined by 1H NMR.

■

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.5b01019. NMR spectra of the compounds and additional X-ray crystallographic details for compounds 3b and 9a−c (PDF) Crystallographic files for compounds 3b and 9a−c (CIF)

■

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] (A. Kostyuk). *Tel: +39-049-8275216. Fax: +39-049-8275223. E-mail: andrea.biffi[email protected] (A. Biffis). Notes

The authors declare no competing financial interest.

■

REFERENCES

(1) Crabtree, R. H. The Organometallic Chemistry of the Transition Metals, 6th ed.; Wiley: Hoboken, NJ, 2014. (2) (a) Slone, C. S.; Weinberger, D. A.; Mirkin, C. A. Prog. Inorg. Chem. 1999, 48, 233−350. (b) Braunstein, P.; Naud, F. Angew. Chem., Int. Ed. 2001, 40, 680−699. (c) Zhang, W.−H.; Chien, S. W.; Hor, T. S. A. Coord. Chem. Rev. 2011, 255, 1991−2024. (3) General references on NHC ligands: (a) Nolan, S. P., Ed. NHeterocyclic Carbenes, Effective Tools for Organometallic Synthesis; WileyVCH: Weinheim, 2014. (b) Diez-Gonzalez, S., Ed. N-Heterocyclic Carbenes: From Laboratory Curiosities to Efficient Synthetic Tools; RSC Catalysis Series, RSC: Cambridge, 2010. (c) Cazin, C. S. J., Ed. NHeterocyclic Carbenes in Transition Metal Catalysis and Organocatalysis, Catalysis by Metal Complexes, Vol. 32; Springer: Heidelberg, 2010. (4) General reviews on N-heterocyclic carbenes: (a) Hopkinson, M. N.; Richter, C.; Schedler, M.; Glorius, F. Nature 2014, 510, 485−496. (c) Melaimi, M.; Soleilhavoup, M.; Bertrand, G. Angew. Chem., Int. Ed. 2010, 49, 8810−8849. (d) Hahn, F. E.; Jahnke, M. C. Angew. Chem., Int. Ed. 2008, 47, 3122−3172. (5) (a) Biffis, A.; Baron, M.; Tubaro, C. Adv. Organomet. Chem. 2015, 63, 203−288. (b) Gaillard, S.; Renaud, J.-L. Dalton Trans. 2013, 42, 7255−7270. (c) Gu, S.; Huang, J.; Chen, W. Youji Huaxue 2013, 33, 715−737. (d) Bierenstiel, M.; Cross, E. D. Coord. Chem. Rev. 2011, 255, 574−590. (e) Kühl, O. Functionalised N-Heterocyclic Carbene Complexes; Wiley: Hoboken, NJ, 2010. (f) Poyatos, M.; Mata, J. A.; Peris, E. Chem. Rev. 2009, 109, 3677−3707. (g) Normand, A. T.; Cavell, K. J. Eur. J. Inorg. Chem. 2008, 2008, 2781−2800. (h) Kühl, O. Chem. Soc. Rev. 2007, 36, 592−607. (i) Lee, H. M.; Lee, C.-C.; Cheng, P.-Y. Curr. Org. Chem. 2007, 11, 1491−1524. (j) Pugh, D.; H

DOI: 10.1021/acs.organomet.5b01019 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics (24) (a) Alici, B.; Ç etinkaya, E.; Ç etinkaya, B. Heterocycles 1997, 45, 29−36. (b) Paczal, A.; Bényei, A. C.; Kotschy, A. J. Org. Chem. 2006, 71, 5969−5979. (25) Sheldrick, G. M. SHELXS97 Program for the Solution of Crystal Structure; University of Goettingen: Goettingen, Germany, 1997. (26) Sheldrick, G. M. SHELXL97 Program for the Refinement of Crystal Structures; University of Goettingen: Goettingen, Germany, 1997. (27) Watkin, D. J.; Prout, C. K.; Carruthers, J. R.; Betteridge, P. W. CRYSTALS issue 10; Chemical Crystallography Laboratory, University of Oxford, 1996. (28) Carruthers, J. R.; Watkin, D. J. Acta Crystallogr., Sect. A: Cryst. Phys., Diffr., Theor. Gen. Crystallogr. 1979, 35, 698−699.

I

DOI: 10.1021/acs.organomet.5b01019 Organometallics XXXX, XXX, XXX−XXX