Complexes

Abstract

The present invention provides a palladium(II) complex of formula (1). ##STR00001## R.sub.12, m, and X are described in the specification. The invention also provides a process for the preparation of the complex, and its use in carbon-carbon and carbon-heteroatom coupling reactions.

Claims

1. A palladium(II) complex of formula (1): ##STR00105## wherein: Cy is cyclohexyl; R.sub.12 is an organic group having 1-20 carbon atoms; m is 0, 1, 2, 3, 4 or 5; and X is a coordinating anionic ligand.

2. A palladium(II) complex according to claim 1, wherein R.sub.12 is selected from the group consisting of substituted and unsubstituted straight-chain alkyl, substituted and unsubstituted branched-chain alkyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aryl, and substituted and unsubstituted heteroaryl wherein the heteroatoms are independently selected from sulfur, nitrogen and oxygen.

3. A palladium(II) complex according to claim 1, wherein X is a halo group or a trifluoroacetate group.

4. A palladium(II) complex according to claim 1, wherein the complex of formula (1) is selected from the group consisting of: ##STR00106##

5. A process for the preparation of a complex of formula (1), the process comprising the step of reacting a complex of formula (3) with a monodenatate biaryl ligand of formula (4) to form the complex of formula (1), ##STR00107## wherein, Cy is cyclohexyl; R.sub.12 is an organic group having 1-20 carbon atoms; m is 0, 1, 2, 3, 4 or 5; and X is a coordinating anionic ligand.

6. A process for carrying out a carbon-carbon coupling reaction or a carbon-heteroatom coupling reaction in the presence of a catalyst, the process comprising the use of a complex of formula (1) as defined in claim 1.

7. The process of claim 6, wherein the carbon-carbon coupling reaction is (a) a Heck reaction; (b) a Suzuki reaction; (c) a Sonogashira reaction; or (d) a Negishi reaction and the carbon-heteroatom coupling reaction is a Buchwald-Hartwig amination reaction.

Description

(1) The invention will now be described by way of the following non-limiting examples and with reference to the following figures in which:

(2) FIG. 1 is a .sup.1H NMR spectrum of Pd(π-allyl)(BrettPhos)Cl.

(3) FIG. 2 is a .sup.1H NMR spectrum of Pd(π-crotyl)(BrettPhos)Cl.

(4) FIG. 3 is a .sup.1H NMR spectrum of Pd(π-cinnamyl)(BrettPhos)Cl.

(5) FIG. 4 is a .sup.1H NMR spectrum of Pd(π-allyl)(JackiePhos)Cl.

(6) FIG. 5 is a .sup.1H NMR spectrum of (π-crotyl)Pd(CyBippyPhos)Cl.

(7) FIG. 6 illustrates the rate of conversion in the α-arylation of acetophenone with 4-chloroanisole using (π-allyl)Pd(XPhos)Cl, (π-crotyl)Pd(XPhos)Cl, (π-cinnamyl)Pd(XPhos)Cl, 3.sup.rd generation XPhos palladacycle and (π-allyl)Pd(XPhos)Cl with 1 mol % added carbazole.

EXAMPLES

(8) All solvents and reagents were purchased from commercial sources and used as received. All catalysts, ligands or precious metal precursors were obtained from Johnson Matthey Catalysis or Alfa Aesar. Flash chromatography was performed either on a Teledyne Isco CombiFlashRf using 12 g RediSepRf silica gel cartridges. .sup.31P, .sup.1H and .sup.13C NMR spectra were recorded on a 400 MHz spectrometer, with chemical shifts reported relative to residual solvent as internal references (CDCl.sub.3: 7.26 ppm for .sup.1H NMR and 77.26 ppm for .sup.13C NMR, C.sub.6D.sub.6: 7.16 ppm for .sup.1H NMR and 128.06 ppm .sup.13C NMR, DMSO-d6: 2.50 ppm for .sup.1H NMR and 39.52 ppm for .sup.13C NMR, toluene-d8: 2.08 ppm for .sup.1H NMR and 20.43 ppm for .sup.13C NMR), unless otherwise stated, while .sup.31P.sup.1H NMR spectra were externally referenced to 85% H.sub.3PO.sub.4. The following abbreviations were used to explain the multiplicities: s=singlet, d=doublet, t=triplet, q=quartet, quint=quintet, sept=septet, m=multiplet, b=broad, app t=apparent triplet, app d=apparent doublet, br=broad. Elemental analyses were sent to Robertson Microlit Laboratories, Inc. All reactions were carried out in individual Schlenk flasks under a nitrogen atmosphere. The purity of the isolated products was >95% as determined by .sup.1H NMR, GC/MS or elemental analysis unless noted otherwise.

(9) Crystallographic data were obtained at 120K on a APEX Bruker-AXS CCD X-ray diffractometer equipped with a monocap collimator. Structures were solved with SHELXTL software. These data was obtained from University of Delaware X-ray Crystallography Laboratory of the Department of Chemistry and Biochemistry.

(10) General Procedure for the Preparation of [Pd(Optionally Substituted (R.sub.12).sub.n-Allyl)(X)].sub.2 Complexes:

(11) Distilled H.sub.2O in a three-necked roundbottom flask is purged with nitrogen for 30 minutes. PdCl.sub.2 and KCl are subsequently added to the flask and the solution is stirred at room temperature for 1 h. Then, optionally substituted (R.sub.4).sub.n-allyl chloride is added and the resulting reaction mixture is stirred at room temperature overnight (18-20 hrs). The reaction is extracted with chloroform, and the aqueous layer washed with chloroform three times. The organic layers are combined, dried over MgSO.sub.4, filtered and concentrated in vacuo. The crude product is recrystallised from chloroform and methyl tert-butyl ether, and the resulting solid is isolated by filtration and dried in vacuo.

(12) [Pd(π-cinnamyl)Cl].sub.2

(13) ##STR00033##

(14) PdCl.sub.2 (590 mg, 3.33 mmol); KCl (473 mg, 6.67 mmol); cinnamyl chloride (1.39 mL, 9.99 mmol); H.sub.2O (83 mL). The dimer is obtained as a yellow solid.

(15) [Pd(π-1-crotyl)Cl].sub.2

(16) ##STR00034##

(17) PdCl.sub.2 (590 mg, 3.33 mmol); KCl (473 mg, 6.67 mmol); crotyl chloride (0.97 mL, 9.99 mmol); H.sub.2O (83 mL). The dimer is obtained as a yellow solid.

(18) [Pd(π-prenyl)Cl].sub.2

(19) ##STR00035##

(20) PdCl.sub.2 (590 mg, 3.33 mmol); KCl (473 mg, 6.67 mmol); 1-chloride-3-methyl-2-butene (1.13 mL, 9.99 mmol); H.sub.2O (83 mL). The dimer is obtained as a yellow solid.

(21) [Pd(π-methallyl)Cl].sub.2

(22) ##STR00036##

(23) PdCl.sub.2 (590 mg, 3.33 mmol); KCl (473 mg, 6.67 mmol); 3-chloride-2-methyl-1-propene (0.98 mL, 9.99 mmol); H.sub.2O (83 mL). The dimer is obtained as a yellow solid (269 mg, 41%).

Example 1 (According to the Invention)

Representative Procedure for the Preparation of [Pd(Optionally Substituted (R.SUB.12.).SUB.m.-Allyl)(Ligand)(X) Complexes

(24) A dry Schlenk tube is charged with the ligand (4.74 mmol) and [(optionally substituted (R.sub.12).sub.m-allyl)PdCl].sub.2 (2.36 mmol). The tube is evacuated and backfilled with nitrogen a total of three times. 10 mL of anhydrous solvent (such as THF or toluene) is added and the mixture is stirred at room temperature for a period of time (e.g. 20 minutes). Pentane (5 mL) or hexanes is added to fully precipitate the product. The product is collected by vacuum filtration, washed (3×10 mL of pentane, or hexanes) and dried under vacuum.

(25) Pd(π-allyl)(JohnPhos)Cl

(26) ##STR00037##

(27) Following the representative procedure: [(allyl)PdCl].sub.2 (1.00 g, 2.75 mmol); JohnPhos (1.64 g, 5.50 mmol); toluene (13.2 mL); 1 h. Product obtained as a pale yellow solid (2.46 g, 93%); .sup.1H NMR (400 MHz, CDCl.sub.3, δ): 7.93-7.82 (m, 1H), 7.71-7.57 (m, 2H), 7.50-7.19 (m, 6H), 4.85-2.60 (m, 5H), 1.90-1.10 (m, 18H); .sup.13C NMR (100 MHz, CDCl.sub.3, δ): 149.0, 148.8, 142.2 (2 peaks), 134.8, 134.6, 133.6 (2 peaks), 130.4, 129.8, 129.7, 129.6, 128.1, 126.3, 125.4, 125.3, 113.3, 113.2, 81.7 (br), 57.6 (br), 37.2, 30.9 [Observed complexity due to C—P coupling]; .sup.31P NMR (162 MHz, CDCl.sub.3, δ): 57.3; Anal. calcd. for C.sub.23H.sub.32ClPPd: C, 57.39; H, 6.70. Found C, 57.35; H, 6.53.

(28) (π-crotyl)Pd(JohnPhos)Cl

(29) ##STR00038##

(30) A dry Schlenk flask equipped with a Teflon-coated magnetic stir bar is charged with 1.00 g (2.54 mmol) of [(crotyl)PdCl].sub.2 (0.50 equiv) followed by 1.52 g (5.08 mmol) of JohnPhos. The flask is fitted with a rubber septum and it is evacuated and backfilled with nitrogen. This evacuation/nitrogen backfill cycle is repeated two additional times. Solvent (anhydrous toluene) is added via syringe and the react ion mixture is stirred at rt for 1.25 hours. Pentane (25 mL) is then added to fully precipitate the product. The solid materials are then collected by suction filtration, washed with additional pentane (or hexanes), and dried in vacuo to give 2.40 g (4.84 mmol, 95%) of the title compound as a yellow solid. .sup.1H NMR (400 MHz, CDCl.sub.3, δ): 7.87 (s, 1H), 7.50-7.75 (m, 2H), 7.10-7.50 (m, 6H), 3.98-4.23 (m, 1H), 3.60-3.83 (m, 1H), 2.99-3.11 (m, 1H), 1.20-1.76 (m, 22H). .sup.13C NMR (101 MHz, CDCl.sub.3, δ): 149.0, 148.8, 142.1 (2 peaks), 135.0, 133.9 (2 peaks), 130.4, 130.0, 129.8, 129.7, 127.9, 126.4, 125.2 (2 peaks), 112.7 (2 peaks), 100.3, 100.0, 52.2, 37.7, 37.6, 37.3, 37.2, 31.7, 31.6, 30.5, 30.4, 17.7, 17.6 [Observed complexity due to C—P coupling].

(31) .sup.31P NMR (162 MHz, CDCl.sub.3, δ): 57.1.

(32) Anal. Calcd. for C.sub.24H.sub.34ClPPd: C, 58.19; H, 6.92. Found: C, 57.91; H, 6.74.

(33) Pd(π-allyl)(SPhos)Cl

(34) ##STR00039##

(35) Following the representative procedure: [(allyl)PdCl].sub.2 (505 mg, 1.39 mmol); SPhos (1.14 g, 2.78 mmol); THF (3 mL); 6 h. Product obtained as a white solid (1.30 g, 79%); .sup.1H NMR (400 MHz, CDCl.sub.3, δ): 7.65 (t, J=8.6 Hz, 1H), 7.42 (t, J=7.4 Hz, 1H), 7.33 (t, J=7.8 Hz, 1H), 7.30-7.22 (m, 1H), 7.06 (dd, J=3.5 Hz, 8.2 Hz, 1H), 6.70-6.44 (m, 2H), 5.24-5.08 (m, 1H), 4.47 (t, J=7.1 Hz, 1H), 3.82-3.60 (m, 6H), 3.40-3.22 (m, 1H), 3.02 (dd, J=9.4 Hz, 13.7 Hz, 1H), 2.41-2.00 (m, 3H), 2.00-0.90 (m, 20H); .sup.13C NMR (100 MHz, CDCl.sub.3, δ): 158.0, 140.6, 140.5, 134.8, 134.7, 133.0, 132.9, 131.3, 131.0, 129.5, 128.9, 125.9, 125.8, 119.4, 119.4, 115.9, 115.8, 109.9, 104.2, 103.1, 82.2, 81.9, 55.4, 54.7, 36.2 (4 peaks), 29.8, 29.0, 27.3, 27.2, 26.1 [Observed complexity due to C—P coupling]; .sup.31P NMR (162 MHz, CDCl.sub.3, δ): 31.8; Anal. calcd. for C.sub.29H.sub.40O.sub.2ClPPd: C, 58.67; H, 6.79. Found C, 58.93; H, 6.76.

(36) Single crystals of Pd(π-allyl)(SPhos)Cl are obtained by slow cooling of a 1:1 THF/pentane solution in the freezer.

(37) Pd (π-crotyl) (SPhos)Cl

(38) ##STR00040##

(39) Following the representative procedure: [(crotyl)PdCl].sub.2 (501 mg, 1.27 mmol); SPhos (1.05 g, 2.56 mmol); THF (5 mL); 6 h. Product obtained as an off-white solid (1.28 g, 83%); .sup.1H NMR (400 MHz, C.sub.6D.sub.6, δ): 7.58 (t, J=7.7 Hz, 1H), 7.17-7.04 (m, 4H), 6.42 (d, J=8.5 Hz, 1H), 6.28 (d, J=8.3 Hz, 1H), 4.69-4.58 (m, 1H), 3.77-3.62 (m, 1H), 3.53 (s, 3H), 3.25 (s, 3H), 3.20 (d, J=6.6 Hz, 1H), 2.52-2.29 (m, 2H), 2.20-1.15 (m, 24H); .sup.13C NMR (100 MHz, C.sub.6D.sub.6, δ): 158.0, 157.7, 141.8, 141.7, 133.4 (2 peaks), 133.2, 133.1, 132.0, 131.7, 129.1 (2 peaks), 128.2, 125.6, 125.5, 119.8, 119.7, 114.1 (2 peaks), 103.7, 102.8, 99.8, 99.6, 54.8, 54.6, 48.4, 38.0, 37.8, 37.3, 37.1, 29.9, 28.5, 28.3, 27.4 (2 peaks), 27.3, 27.1, 27.0 (2 peaks), 26.9, 26.1, 17.1 (2 peaks) [Observed complexity due to C—P coupling]; .sup.31P NMR (162 MHz, C.sub.6D.sub.6, δ): 28.9; Anal. calcd. for C.sub.30H.sub.42O.sub.2ClPPd: C, 59.31; H, 6.97. Found C, 59.15; H, 7.17

Pd(π-cinnamyl)(SPhos)Cl

(40) ##STR00041##

(41) Following the representative procedure: [(cinnamyl)PdCl].sub.2 (1.00 g, 1.93 mmol); SPhos (1.59 g, 3.86 mmol); toluene (4.3 mL); 1 h. Product obtained as a yellow solid (2.56 g, 99%); .sup.1H NMR (400 MHz, CDCl.sub.3, δ): 7.68 (t, J=8.5 Hz, 1H), 7.48-7.20 (m, 8H), 7.08-7.02 (m, 1H), 6.60 (d, J=8.3 Hz, 1H), 5.53-5.42 (m, 1H), 4.78-4.67 (m, 1H), 3.67 (s, 6H), 3.43-2.20 (m, 4H), 2.01-1.88 (m, 2H), 1.80-1.51 (m, 8H), 1.46-1.05 (m, 10H); .sup.13C NMR (100 MHz, CDCl.sub.3, δ): 157.8, 140.3, 140.2, 136.9, 136.8, 135.0, 134.9, 133.0 (2 peaks), 131.3, 131.0, 129.3, 129.0, 128.4, 128.4, 128.1, 127.6 (2 peaks), 127.5, 125.7, 125.6, 119.4 (2 peaks), 109.3, 109.2, 103.6, 101.7, 101.4, 55.3, 50.0, 36.1, 35.9, 29.8, 29.7, 29.2, 27.3, 27.2, 27.0, 26.9, 26.1 [Observed complexity due to C—P coupling]; .sup.31P NMR (162 MHz, CDCl.sub.3, δ): 37.5; Anal. calcd. for C.sub.35H.sub.44O.sub.2ClPPd: C, 62.78; H, 6.62. Found C, 62.66; H, 6.54.

(42) Single crystals for X-ray analysis of Pd(π-cinnamyl)(SPhos)Cl are obtained by slow cooling of a 1:1 THE/pentane solution in the freezer.

Pd(π-allyl)(RuPhos)Cl

(43) ##STR00042##

(44) Following the representative procedure: [(allyl)PdCl].sub.2 (503 mg, 1.43 mmol); RuPhos (1.29 g, 2.77 mmol); THF (2 mL); 1 h. Product obtained as a white solid (1.52 g, 85%); .sup.1H NMR (400 MHz, C.sub.6D.sub.6, δ): 7.60 (t, J=8.7 Hz, 1H), 7.18-7.05 (m, 4H), 6.96-6.86 (m, 1H), 6.92 (d, J=7.7 Hz, 1H), 6.32 (d, J=7.5 Hz, 1H), 5.03-4.91 (m, 1H), 4.49 (t, J=7.4 Hz, 1H), 4.46-4.30 (m, 1H), 4.22-4.08 (m, 1H), 3.37-3.22 (m, 1H), 3.01 (dd, J=9.7 Hz, 13.4 Hz, 1H), 2.55-2.04 (m, 5H), 2.03-0.80 (m, 30H); .sup.13C NMR (100 MHz, C.sub.6D.sub.6, δ): 157.2, 156.7, 141.3 (2 peaks), 134.4, 134.3, 132.7, 132.6, 132.4, 132.1, 128.7 (2 peaks), 128.3, 127.9, 125.4, 125.3, 122.5, 122.4, 115.3 (2 peaks), 106.4, 105.5, 80.1, 79.8, 70.2, 69.9, 55.8, 36.2, 36.0, 35.5, 35.3, 29.5, 29.4, 27.1, 27.0, 26.2, 25.5, 22.3, 22.2, 21.6, 21.3 [Observed complexity due to C—P coupling]; .sup.31P NMR (162 MHz, C.sub.6D.sub.6, δ): 34.6; Anal. calcd. for C.sub.33H.sub.48O.sub.2ClPPd: C, 61.02; H, 7.45. Found C, 60.87; H, 7.42.

(45) Single crystals of Pd(π-allyl)(RuPhos)Cl for X-ray analysis are obtained by slow cooling of a 1:1 THF/hexanes solution in the freezer.

Pd(π-crotyl)(RuPhos)Cl

(46) ##STR00043##

(47) Following the representative procedure: [(crotyl)PdCl].sub.2 (1.022 g, 5.09 mmol); RuPhos (2.37 g, 10.18 mmol); THF (2.5 mL); 2 h. Product obtained as a pale yellow solid (2.93 g, 87%); .sup.1H NMR (400 MHz, C.sub.6D.sub.6, δ): 7.64 (t, J=8.4 Hz, 1H), 7.24-7.09 (m, 3H), 7.06-7.00 (m, 1H), 6.50 (d, J=7.9 Hz, 1H), 6.34 (d, J=7.6 Hz, 1H), 4.90-4.80 (m, 1H), 4.58-4.45 (m, 1H), 4.31-4.18 (m, 1H), 3.82-3.70 (m, 1H), 3.34-3.26 (m, 1H), 2.57-0.80 (m, 38H); .sup.13C NMR (100 MHz, C.sub.6D.sub.6, δ): 157.4, 156.9, 142.3, 142.2, 133.9, 133.8, 132.8 (2 peaks), 132.5, 128.9 (2 peaks), 128.2, 125.6, 125.5, 122.7 (2 peaks), 114.7 (2 peaks), 106.3, 105.4, 99.4, 99.1, 70.2, 70.0, 50.7, 37.5, 37.3, 36.7, 36.5, 30.0, 29.2, 27.4, 27.3, 27.1, 26.4, 22.5, 22.4, 21.6, 21.4, 17.4 (2 peaks) [Observed complexity due to C—P coupling]; .sup.31P NMR (162 MHz, C.sub.6D.sub.6, δ): 33.2; HRMS-ESI m/z: [M-Cl], calcd. for C.sub.33H.sub.48O.sub.2PPd, 627.2583; found 627.2554.

(48) Single crystals of Pd(π-crotyl)(RuPhos)Cl for X-ray analysis are obtained by by slow cooling of a 1:1 THF/hexanes solution in the freezer.

Pd(π-cinnamyl)(RuPhos)Cl

(49) ##STR00044##

(50) Following the representative procedure: [(cinnamyl)PdCl].sub.2 (1.00 g, 1.93 mmol); RuPhos (1.80 g, 3.86 mmol); THF (4 mL); 2 h. Product obtained as a yellow solid (2.13 g, 76%); .sup.1H NMR (400 MHz, CDCl.sub.3, δ): 7.78-7.68 (m, 1H), 7.46 (d, J=7.5 Hz, 1H), 7.35-7.18 (m, 7H), 6.92-6.87 (m, 1H), 6.55 (d, J=8.2 Hz, 1H), 5.72-5.58 (m, 1H), 4.91-4.77 (m, 1H), 4.52-4.39 (m, 1H), 3.00-2.50 (m, 1H), 2.31-2.19 (m, 2H), 2.05-1.94 (m, 2H), 1.74-1.49 (m, 8H), 1.44-0.89 (m, 24H); .sup.13C NMR (100 MHz, CDCl.sub.3, δ): 156.9, 140.1, 137.1 (2 peaks), 135.1, 132.8, 132.7, 131.8, 131.5, 128.7, 128.4, 127.5 (2 peaks), 127.4, 125.2, 125.1, 122.4 (2 peaks), 109.7, 109.6, 106.0, 100.3, 100.0, 70.4, 52.6, 35.0, 24.8, 30.0, 29.2. 27.0, 26.9, 26.8, 26.0, 22.4, 22.0, 21.8 [Observed complexity due to C—P coupling]; .sup.31P NMR (162 MHz, CDCl.sub.3, δ): 44.0; HRMS-ESI m/z: [M−Cl], calcd. for C.sub.39H.sub.52O.sub.2PPd, 689.2740; found 689.2739.

Pd(π-allyl)(XPhos)Cl

(51) ##STR00045##

(52) Following the representative procedure: [(allyl)PdCl].sub.2 (858 mg, 2.36 mmol); XPhos (2.56 g, 5.37 mmol); THF (5 mL); 3 h. Product obtained as a yellow solid (3.11 g, 97%), product contains ˜5 mol % of THF; .sup.1H NMR (400 MHz, CDCl.sub.3, δ): 7.98-7.84 (m, 1H), 7.40-7.27 (m, 2H), 7.07-6.99 (m, 3H), 5.47-5.26 (m, 1H), 4.54 (t, J=7.1 Hz, 1H), 3.51 (dd, J=9.3 Hz, 13.6 Hz, 1H), 3.12-3.01 (m, 1H), 3.00-2.88 (m, 1H), 2.70-2.42 (m, 2H), 2.41-2.10 (m, 3H), 1.92-0.73 (m, 38H); .sup.13C NMR (100 MHz, CDCl.sub.3, δ): 148.7, 146.2, 142.1, 136.6, 136.4, 136.3, 133.7, 133.6, 131.8, 131.6, 128.0 (2 peaks), 125.5, 125.4, 120.7, 116.0, 116.0, 79.3, 79.0, 55.7, 34.4, 34.1, 33.9, 31.3, 30.4, 29.0, 27.1, 27.0, 26.8, 26.7, 25.6, 25.4, 23.9, 22.3 [Observed complexity due to C—P coupling], peaks attributable to THF were observed at 67.7, 25.8; .sup.31P NMR (162 MHz, CDCl.sub.3, δ): 48.0; Anal. calcd. for C.sub.36H.sub.54ClPPd: C, 65.55; H, 8.25. Found C, 65.79; H, 8.01.

Pd (π-crotyl) (XPhos)Cl

(53) ##STR00046##

(54) Following the representative procedure: [(crotyl)PdCl].sub.2 (1.00 g, 2.54 mmol); XPhos (2.42 g, 5.08 mmol); toluene (30 mL); 2 h. Product obtained as a white solid (3.11 g, 91%); .sup.1H NMR (400 MHz, CDCl.sub.3, δ): 7.99-7.86 (m, 1H), 7.38-7.29 (m, 2H), 7.18-6.99 (m, 3H), 5.19-5.03 (m, 1H), 4.32-4.13 (m, 1H), 3.00-2.80 (m, 2H), 2.71-2.42 (m, 2H), 2.31-2.02 (m, 3H), 1.95-0.74 (m, 47H); .sup.13C NMR (100 MHz, CDCl.sub.3, δ): 148.7, 146.3, 142.1, 136.9, 136.7, 136.5, 133.7, 133.6, 132.3, 132.0, 128.8, 128.0 (2 peaks), 125.5, 125.4, 120.8, 115.0 (2 peaks), 98.5, 98.2, 50.9, 34.8, 34.2, 31.4, 30.5 (2 peaks), 29.2, 27.2, 27.1, 27.0, 26.9, 26.8, 25.8, 25.7, 24.0, 22.4, 17.2, 17.1 [Observed complexity due to C—P coupling]; .sup.31P NMR (162 MHz, CDCl.sub.3, δ): 50.8; HRMS-ESI m/z: [M−Cl], calcd. for C.sub.37H.sub.56PPd, 637.3154; found 637.3153.

Pd(π-cinnamyl)(XPhos)Cl

(55) ##STR00047##

(56) Following the representative procedure: [(cinnamyl)PdCl].sub.2 (1.00 g, 1.93 mmol); XPhos (1.84 g, 3.86 mmol); toluene (5 mL); 2 h. Product obtained as a yellow solid (2.27 g, 80%), product contains trace residual toluene; .sup.1H NMR (400 MHz, CDCl.sub.3, δ): 8.10-7.95 (m, 1H), 7.52 (d, J=7.5 Hz, 2H), 7.42-7.23 (m, 5H), 7.11-7.01 (m, 3H), 5.87-5.69 (m, 1H), 5.20-5.06 (m, 1H), 3.08-2.90 (m, 2H), 2.73-0.70 (m, 49H), peaks attributable to toluene were observed at 7.17 and 2.36; .sup.13C NMR (100 MHz, CDCl.sub.3, δ): 148.9, 146.4, 142.1, 137.2, 136.9, 136.8, 136.7, 136.6, 133.8, 133.7, 132.4, 132.2, 129.0, 128.6, 128.4, 128.1, 127.6 (2 peaks), 125.7, 125.6, 125.2, 121.0, 109.7, 109.6, 99.4, 99.1, 51.9, 34.5, 34.3, 31.7, 30.6, 29.2, 27.3, 27.2, 27.0, 26.9, 26.0, 25.7, 24.1, 22.5 [Observed complexity due to C—P coupling], peaks attributable to toluene were observed at 137.7, 21.4; .sup.31P NMR (162 MHz, CDCl.sub.3, δ): 54.3; Anal. calcd. for C.sub.36H.sub.54ClPPd: C, 68.56; H, 7.95. Found C, 68.85; H, 7.93.

Pd(π-allyl) (BrettPhos)Cl

(57) ##STR00048##

(58) Following the representative procedure: [(allyl)PdCl].sub.2 (502 mg, 1.38 mmol); BrettPhos (1.48 g, 2.76 mmol); toluene (6 mL); 1 h. Product obtained as an off-white solid (1.95 g, 99%); .sup.1H NMR (400 MHz, CDCl.sub.3, δ): complex spectrum (see FIG. 1); .sup.31P NMR (162 MHz, CDCl.sub.3, δ): 54.1, 48.7; Anal. calcd. for C.sub.38H.sub.58O.sub.2ClPPd: C, 63.42; H, 8.12. Found C, 63.17; H, 8.16.

Pd (π-crotyl)(BrettPhos)Cl

(59) ##STR00049##

(60) Following the representative procedure: [(crotyl)PdCl].sub.2 (303 mg, 0.769 mmol); BrettPhos (827 mg, 1.53 mmol); toluene (2 mL); 1 h. Product obtained as an off-white solid (1.04 g, 92%); .sup.1H NMR (400 MHz, CDCl.sub.3, δ): complex spectrum (see FIG. 2); .sup.31P NMR (162 MHz, CDCl.sub.3, δ): 41.4; Anal. calcd. for C.sub.39H.sub.60O.sub.2ClPPd: C, 63.84; H, 8.24. Found C, 65.01; H, 8.57

Pd (π-cinnamyl)(BrettPhos)Cl

(61) ##STR00050##

(62) Following the representative procedure: [(cinnamyl)PdCl].sub.2 (503 mg, 0.971 mmol); BrettPhos (1.04 g, 1.94 mmol); toluene (4 mL); 0.5 h. Product obtained as a yellow solid (1.34 g, 87%); .sup.1H NMR (400 MHz, CDCl.sub.3, δ): complex spectrum (see FIG. 3); .sup.31P NMR (162 MHz, CDCl.sub.3, δ): 43.9; Anal. calcd. for C.sub.44H.sub.62O.sub.2ClPPd: C, 6.41; H, 7.85. Found C, 66.44; H, 8.15.

Pd (π-allyl)(JackiePhos)Cl

(63) ##STR00051##

(64) Following the representative procedure: [(allyl)PdCl].sub.2 (183 mg, 0.500 mmol); JackiePhos (797 mg, 1.00 mmol); toluene (5 mL); 1 h. Product obtained as a white solid (529 mg, 54%); .sup.1H NMR (400 MHz, CDCl.sub.3, δ): complex spectrum (see FIG. 4); .sup.31P NMR (162 MHz, CDCl.sub.3, δ): 18.1; Anal. calcd. for C.sub.42H.sub.42F.sub.12O.sub.2ClPPd: C, 51.50; H, 4.32. Found C, 51.52; H, 4.15.

(65) Pd(π-allyl)(CyBippyPhos)Cl

(66) ##STR00052##

(67) Following the representative procedure: [(allyl)PdCl].sub.2 (245 mg, 0.671 mmol); CyBippyPhos (750 mg, 1.34 mmol); THF (4.5 mL); 0.5 h. Product obtained as a pale yellow solid (220 mg, 22%).

(68) Pd(π-allyl)(CyBippyPhos)Cl may also be prepared by the following procedure:

(69) A dry 20 mL scintillation vial is charged with 245 mg (0.67 mmol) of [(allyl)PdCl].sub.2 and transferred into a nitrogen-filled glove box. The vial is then charged with 750 mg (1.34 mmol) of CyBippyPhos. 4 mL of toluene is added and the mixture is stirred at rt for 30 minutes. During the stir time, the mixture becomes thick and stirring is difficult. An additional 4 mL of toluene is added to allow stirring to continue. The product is fully precipitated by the addition of 8 mL of hexanes. The solid is collected by vacuum filtration in air and washed with 3×10 mL of hexanes. The solid is dried in vacuo to give 913 mg (1.23 mmol, 92%) of the title compound as an off-white solid. The product contains <2 wt % of residual toluene.

(70) .sup.1H NMR (400 MHz, CDCl.sub.3, δ): 7.99 (s, 1H), 7.44-7.18 (m, 15H), 6.68-6.55 (m, 1H), 5.30-4.99 (m, 1H), 4.60-4.50 (m, 1H), 3.54-3.33 (m, 1H), 2.88-2.78 (m, 1H), 2.20-0.77 (m, 22H), 0.48-0.30 (m, 1H); .sup.31P NMR (162 MHz, CDCl.sub.3, δ): 25.2, 23.2; HRMS-ESI m/z: [M-Cl], calcd. for C.sub.37H.sub.56PPd, 637.3154; found 637.3153. Anal. calcd. for C.sub.39H.sub.44N.sub.4ClPPd: C, 63.16; H, 5.98; N, 7.55. Found C, 63.22; H, 6.14; N, 7.30.

(π-crotyl)Pd(CyBippyPhos)Cl

(71) ##STR00053##

(72) A dry Schlenk flask is charged with 264 mg (0.67 mmol) of [(crotyl)PdCl].sub.2 and transferred into a nitrogen-filled glove box. The flask is then charged with 750 mg (1.34 mmol) of CyBippyPhos. 8 mL of toluene is added and the mixture is stirred at rt for 1 hour. The product is precipitated by the addition of 20 mL of pentane with cooling in an ice bath. The solid is collected by vacuum filtration in air, washed with 3×10 mL of hexanes, and dried in vacuo to give 904 mg (1.10 mmol, 83%) of the title compound as an off-white solid. The product is a ⅔ toluene adduct, which is broken by the dissolution in CH.sub.2Cl.sub.2 and evaporating the solvent under reduced pressure at 60° C.

(73) .sup.1H NMR (400 MHz, CDCl.sub.3, δ): complex spectrum (see FIG. 5).

(74) .sup.13C NMR (101 MHz, CDCl.sub.3, δ): 147.2, 142.2, 142.0, 140.5, 140.4, 140.0, 139.9, 137.9, 137.6, 137.3, 137.1, 131.4, 131.3, 130.4, 129.1 (2 peaks), 129.0, 128.7, 128.6 (2 peaks), 128.5, 128.2 (2 peaks), 127.6, 127.5, 126.2 (2 peaks), 126.1, 125.3, 120.1, 119.8, 116.9, 116.8, 116.4, 116.3, 115.8 (2 peaks), 115.3 (2 peaks), 100.9, 100.6, 100.4, 52.0, 50.6, 34.9, 34.7, 34.4, 34.1, 30.6, 29.9 (2 peaks), 29.6, 29.5, 28.5, 28.3, 27.9, 27.7, 27.2, 27.0, 26.9, 26.8, 26.7, 26.6, 26.0, 25.8, 22.4, 21.5 [Observed complexity due to C—P coupling].

(75) .sup.31P NMR (162 MHz, CDCl.sub.3, δ): 22.6 (br), 19.8 (br).

(76) HRMS (ESI) m/z [M−Cl].sup.+ Calcd. for C.sub.40H.sub.46NPPd: 719.2495; Found: 719.2510.

Example 2 (Comparative)

Arylation of Acetophenone with 4-Chloroanisole

(77) TABLE-US-00001 catalyst X solvent T C time (h) diarylated:mono:acetophenone.sup.a remarks 1 mol % Br Br Cl Cl Cl toluene (0.25M) toluene (0.25M) toluene (0.25M) toluene (0.25M) toluene (0.25M) 40 40 60 60 60 18 18 18 18 18 11%:81%:7%  1%:65%:33%  0%:37%:63%  0%:46%:54%  0%:36%:64% 1.2:1.0 acetophenone:aryl chloride, isolated yield 60% 1.2:1.0 acetophenone:aryl chloride 2.5 eq KOt-Bu 1 mol % Cl toluene (0.25M) 40 18 39%:37%:61% .sup.aNMR ratios

(78) Representative Procedure: A dry Schlenk tube equipped with a teflon-coated magnetic stir bar is charged with 1 mol % (0.01 mmol) of Pd-precatalyst and 2.00 mmol (2.0 equiv) of t-BuOK. The tube is fitted with a rubber septum and is evacuated and backfilled with nitrogen. This evacuation/backfill procedure is repeated two additional times. 4-Chloroanisole (1.00 mmol, 1 equiv) and acetophenone (1.20 mmol, 1.2 equiv) are added via syringe followed by 4 mL of anhydrous toluene. The tube is placed in a preheated (40-60° C.) oil bath and the mixture is stirred vigorously for 18 h. The tube is then removed from the oil bath and the contents are allowed to cool to room temperature. A sample of the crude reaction mixture is analysed by .sup.1H NMR.

Example 3 (According to the Invention)

Arylation of Acetophenone with 4-Chloroanisole

(79) ##STR00057##

(80) Representative Procedure: A dry Schlenk tube equipped with a teflon-coated magnetic stir bar is charged with 6.5 mg (0.01 mmol) of (R-allyl)Pd(XPhos)Cl and 224 mg (2.00 mmol) of t-BuOK. The tube is fitted with a rubber septum and is evacuated and backfilled with nitrogen. This evacuation/backfill procedure is repeated two additional times. 4-Chloroanisole (129 μL, 1.05 mmol) and acetophenone (117 μL, 1.00 mmol) are added via syringe followed by 4 mL of anhydrous toluene. The tube is placed in a preheated (60° C.) oil bath and the mixture is stirred vigorously for 4 h. The tube is then removed from the oil bath and the contents are allowed to cool to room temperature. A sample is analysed by GC.

(81) A common problem observed in the α-arylation of methyl ketones is the formation of diarylated products. The results of this Example indicate that significantly higher yields and higher selectivity (>20:1) for monoarylation:diarylation of acetophenone with chloroarenes are achieved using (R-allyl)Pd(XPhos)Cl complexes relative to (R-allyl)Pd(AmPhos)Cl complexes (see Example 2). It is important to note that it is the identity of the ligand which determines the catalyst's activity.

Example 4 (According to the Invention)

Amination of 4-Chloroanisole with Morpholine.SUP.[a]

(82) TABLE-US-00002 Catalyst GC Conversion.sup.[b] **1st gen RuPhos PC 66% **2nd gen RuPhos PC  4% **3rd Gen RuPhos PC  5% (allyl)Pd(RuPhos)Cl 80% (crotyl)Pd(RuPhos)Cl 87%/97 %.sup.[c]/100%.sup.[c,d] (cinnamyl)Pd(RuPhos)Cl 95% **1st gen RuPhos PC*  6% (crotyl)Pd(RuPhos)Cl*  5% *with 0.5 mol % added carbazole **comparative PC = palladacycle .sup.[a]Reaction conditions: 4-chloroanisole (1.0 mmol), morpholine (1.2 mmol), NaOtBu (1.2 mmol), catalyst (0.5 mol %), THF (2 mL). .sup.[b]Determined by GC using dodecane as an internal standard. .sup.[c]With 0.5 mol % additional RuPhos added. .sup.[d]Run for 2.5 h.

(83) ##STR00059##

(84) The above data demonstrate that the (R-π-allyl)Pd(L)Cl (L=RuPhos) complexes of the present invention exhibit better activity than the first generation RuPhos palladacycle and significantly better activity than the second and third generation RuPhos palladacycles.

(85) Moreover, the second and third generation Buchwald palladacycle precatalysts release an equivalent of genotoxic carbazole upon activation, unlike the complexes of the present invention. The above data also show that the active catalyst generated from (R-π-allyl)Pd(L)Cl complexes does not suffer from inhibition due to carbazole formation, as do the second and third generation palladacycles.

Example 5 (According to the Invention)

Suzuki-Miyaura Coupling of 3-Chloropyridine and p-Tolylboronic Acid.SUP.[a]

(86) TABLE-US-00003 0 Precatalyst GC Conversion * 3rd gen XPhos palladacycle 65% (Allyl)Pd(XPhos)Cl 68% (Crotyl)Pd(XPhos)Cl 91%/100%.sup.[b] (Cinnamyl)Pd(XPhos)Cl 90% * comparative. .sup.[a]Reaction conditions: 3-Chloropyridine (1.0 mmol), p-tolylboronic acid (1.5 mmol), K.sub.3PO.sub.4 (2.0 mmol), catalyst (2 mol %), THF (2 mL), H.sub.2O (4 mL). .sup.[b]Run for 2 h.

(87) ##STR00061##

(88) A dry Schlenk tube, equipped with a Teflon-coated magnetic stir bar and fitted with a rubber septum, is charged with the precatalyst (0.02 mmol, 2 mol %) and 204 mg (1.50 mmol, 1.50 equiv) of p-tolylboronic acid. The tube is evacuated and backfilled with nitrogen. This evacuation/backfill cycle is repeated two additional times. 3-Chloropyridine (95 μL, 1.00 mmol, 1.00 equiv) is added followed by 2 mL of anhydrous THF and 4.0 mL of 0.5 M K.sub.3PO.sub.4 (aqueous). The contents are stirred vigorously for 30 min. An aliquot is removed and analyzed by gas chromatography.

(89) The (allyl)Pd(XPhos)Cl complex exhibits comparable conversion to the 3.sup.rd generation XPhos palladacycle. However, both (crotyl)Pd(XPhos)Cl and (cinnamyl)Pd(XPhos)Cl promote the Suzuki-Miyaura coupling reaction with higher rates than the 3.sup.rd generation palladacycle.

Example 6 (According to the Invention)

Amination of Aryl/Heteroaryl Chlorides Using (π-Crotyl)Pd(RuPhos)C.SUP.[a]

(90) TABLE-US-00004   96%   95%   97%   99%   98%.sup.[b] .sup.[a]Reaction conditions: ArCl/HetArCl (1.0 mmol), amine (1.2 mmol), NaOtBu (1.2 mmol), catalyst (0.5 mol %), RuPhos (0.5 mol %), THF (2 mL). .sup.[b]1 mol % (π-crotyl)Pd(RuPhos)Cl/1 mol % RuPhos, K.sub.2CO.sub.3, t-AmOH, 110° C., 18 h.

(91) Fast reaction times were observed with 100% conversion reached with 1-2.5 h in all cases with the exception of 4-(thiophen-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine, which required 18 h. The synthesis of 4-(thiophen-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine also demonstrates catalyst activation with the use of a weak base (K.sub.2CO.sub.3), compared to NaOt-Bu.

(92) General Procedure for the Amination Reactions

(93) An oven dried Schlenk tube equipped with a Teflon-coated magnetic stir bar is charged with (π-crotyl)Pd(RuPhos)Cl (0.5-1 mol % as indicated), RuPhos (0.5-1 mol % as indicated), aryl chloride (1.00 mmol, if solid), and NaOt-Bu (1.20 mmol). The tube is evacuated and backfilled with nitrogen. This evacuation/backfill cycle is repeated two additional times. Dodecane (GC standard, 0.20 mmol), the amine (1.20 mmol), aryl chloride (1.00 mmol, if liquid), and anhydrous THF (2 mL) are added sequentially via syringe. The tube is placed in a preheated oil bath and stirred for the indicated time. The tube is then removed from the oil bath and allowed to cool to room temperature. The reaction mixture is diluted with 10 mL of EtOAc and filtered through a pad of Celite. The solution is concentrated in vacuo and the residue is chromatographed on silica gel using a Teledyne ISCO CombiFlashRf.

4-(4-methoxyphenyl)morpholine

(94) ##STR00068##

(95) According to the general procedure, a mixture of 4-chloroanisole (123 μL, 1.00 mmol), morpholine (105 μL, 1.20 mmol), NaOtBu (115 mg, 1.20 mmol), (π-crotyl)Pd(RuPhos)Cl (3.3 mg, 0.005 mmol), RuPhos (2.3 mg, 0.005 mmol), and 2 mL THF are stirred at 80° C. for 2.5 h. The crude material is chromatographed on silica gel with a gradient of 0-20% EtOAc/hexanes as the eluent to give 186 mg (0.96 mmol, 96%) of 4-(4-methoxyphenyl)morpholine as a colorless solid. The spectroscopic data match those previously reported (D. Maiti, B. P. Fors, J. L. Henderson, Y. Nakamura, S. L. Buchwald, Chem. Sci. 2011, 2, 57).

N,N-diethyl-6-methoxypyridin-2-amine

(96) ##STR00069##

(97) According to the general procedure, a mixture of 2-chloro-6-methoxypyridine (119 μL, 1.00 mmol), diethylamine (124 μL, 1.20 mmol), NaOtBu (115 mg, 1.20 mmol), (π-crotyl)Pd(RuPhos)Cl (3.3 mg, 0.005 mmol), RuPhos (2.3 mg, 0.005 mmol), and 2 mL THF are stirred at 80° C. for 70 minutes. The crude material is chromatographed on silica gel with a gradient of 0-5% EtOAc/hexanes as the eluent to give 171 mg (0.95 mmol, 95%) of N,N-diethyl-6-methoxypyridin-2-amine as a colorless oil.

(98) .sup.1H NMR (400 MHz, CDCl.sub.3, δ): 7.33 (t, J=7.5 Hz, 1H), 5.99 (d, J=7.8 Hz, 1H), 5.93 (d, J=7.8 Hz, 1H), 3.86 (s, 3H), 3.49 (q, J=7.0 Hz, 4H), 1.81 (t, J=7.0 Hz, 6H).

(99) .sup.13C NMR (100 MHz, CDCl.sub.3, δ): 163.4, 156.7, 139.8, 96.8, 95.2, 52.9, 42.7, 13.2.

(100) HRMS (ESI) m/z [M+H].sup.+ Calcd. for C.sub.10H.sub.17N.sub.2O: 181.1341. Found: 181.1318

1-(pyrazin-2-yl)indoline

(101) ##STR00070##

(102) According to the general procedure, a mixture of 2-chloropyrazine (89 μL, 1.00 mmol), indoline (135 μL, 1.20 mmol), NaOtBu (115 mg, 1.20 mmol), (π-crotyl)Pd(RuPhos)Cl (3.3 mg, 0.005 mmol), RuPhos (2.3 mg, 0.005 mmol), and 2 mL THF are stirred at 80° C. for 1 hour. The crude material is chromatographed on silica gel with a gradient of 0-50% EtOAc/hexanes as the eluent to give 191 mg (0.97 mmol, 97%) of 1-(pyrazin-2-yl)indoline as a yellow solid.

(103) .sup.1H NMR (400 MHz, CDCl.sub.3, δ): 8.14-8.28 (m, 3H), 8.00 (app d, J=2.6 Hz, 1H), 7.13-7.27 (m, 2H), 6.88-6.93 (m, 1H), 4.05 (t, J=8.7 Hz, 2H), 3.24 (t, J=8.7 Hz, 2H).

(104) .sup.13C NMR (100 MHz, CDCl.sub.3, δ): 151.6, 144.1, 141.8, 134.3, 132.0, 131.3, 127.5, 124.8, 121.6, 114.2, 48.7, 27.9.

(105) Anal. Calcd. for C.sub.12H.sub.11N.sub.3: C, 73.07; H, 5.62; N, 21.30. Found: C, 73.17; H, 5.63; N, 21.42.

N-methyl-N-phenylquinolin-6-amine

(106) ##STR00071##

(107) According to the general procedure, a mixture of 6-chloroquinoline (164 mg, 1.00 mmol), N-methylaniline (130 μL, 1.20 mmol), NaOtBu (115 mg, 1.20 mmol), (π-crotyl)Pd(RuPhos)Cl (3.3 mg, 0.005 mmol), RuPhos (2.3 mg, 0.005 mmol), and 2 mL THF are stirred at 80° C. for 1 hour. The crude material is chromatographed on silica gel with a gradient of 0-50% EtOAc/hexanes as the eluent to give 231 mg (0.99 mmol, 99%) of N-methyl-N-phenylquinolin-6-amine as a yellow oil. The spectroscopic data match those previously reported (M. Tobisu, A. Yasutome, K. Yamakawa, T. Shimasaki, N. Chatani, Tetrahedron 2012, 68, 5157).

4-(thiophen-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine

(108) ##STR00072##

(109) The general procedure is followed with the following modifications: a mixture of 3-chlorothiophene (93 μL, 1.00 mmol), benzomorpholine (140 μL, 1.20 mmol), K.sub.2CO.sub.3 (194 mg, 1.40 mmol), (π-crotyl)Pd(RuPhos)Cl (6.6 mg, 0.01 mmol), RuPhos (4.7 mg, 0.01 mmol), and 2 mL t-AmOH are stirred at 110° C. for 20 hour. The crude material is chromatographed on silica gel with a gradient of 0-5% EtOAc/hexanes as the eluent to give 212 mg (0.98 mmol, 98%) of 4-(thiophen-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine as a yellow oil.

(110) .sup.1H NMR (400 MHz, CDCl.sub.3, δ): 7.30 (dd, J=3.2 Hz, 5.2 Hz, 1H), 7.07 (dd, J=1.4 Hz, 5.2 Hz, 1H), 6.92-6.98 (m, 1H), 6.85-6.91 (m, 1H), 6.81 (dd, J=1.4 Hz, 3.2 Hz, 1H), 6.73-6.81 (m, 2H), 4.33 (t, J=4.5 Hz, 2H), 3.69 (t, J=4.4 Hz, 2H).

(111) .sup.13C NMR (100 MHz, CDCl.sub.3, δ): 146.1, 144.5, 133.1, 125.4, 124.1, 121.2, 120.1, 117.0, 116.3, 112.3, 64.5, 49.0.

(112) Anal. Calcd. for C.sub.12H.sub.11NOS: C, 66.33; H, 5.10; N, 6.45. Found: C, 66.42; H, 5.24; N, 6.42.

Example 7 (According to the Invention)

Suzuki-Miyaura Reactions Using (π-Crotyl)Pd(XPhos)Cl.SUP.[a]

(113) TABLE-US-00005   95% rt, 2 h   98% 45° C., 1 h   94% rt, 1 h   88% rt, 30 min   92% rt, 2 h   80%.sup.[b] 45° C., 5 h .sup.[a]Reaction conditions: HetArCl (1.0 mmol), ArB(OH).sub.2 (1.5 mmol), K.sub.3PO.sub.4 (2.0 mmol), catalyst (2 mol %), THF (2 mL), H.sub.2O (4 mL). .sup.[b]Isolated as the hydromethanesulfonate salt for ease of purification.

(114) Using (crotyl)Pd(XPhos)Cl catalyst, a range of heteroaryl chlorides may be coupled with challenging aryl and heteroaryl boronic acids with uniformly high yields, including those which are prone to rapid protodeboronation, at or slightly above room temperature (up to 45° C.) due to the fast generation of the active “L-Pd(0)”. For example, 2-thienylboronic acid, 2-furanboronic acid, and 2,6-difluorophenylboronic acid were all coupled in high yield with short reaction times (≤1 hour).

(115) General Procedure for the Suki-Miyaura Couplings

(116) An oven dried Schlenk tube equipped with a Teflon-coated magnetic stir bar is charged with (π-crotyl)Pd(XPhos)Cl (2 mol %), heteroaryl chloride (1.00 mmol, if solid), and aryl/heteroarylboronic acid (1.5 mmol). The tube is evacuated and backfilled with nitrogen. This evacuation/backfill cycle is repeated two additional times. The heteroaryl chloride (1.00 mmol, if liquid), anhydrous THF (2 mL), and aqueous 0.5 M K.sub.3PO.sub.4 (4.0 mL) are added sequentially via syringe. The tube is stirred at room temperature or placed in a preheated oil bath at 45° C. as indicated and stirred for the indicated time. If heated, the tube is then removed from the oil bath and allowed to cool to room temperature. The reaction mixture is diluted with 10 mL of EtOAc and 10 mL of H.sub.2O, and then the aqueous phase is extracted with 3×10 mL of EtOAc. The combined organic extracts are dried over anhydrous MgSO.sub.4, filtered, and concentrated in vacuo. The residue is chromatographed on silica gel using a Teledyne ISCO CombiFlashRf, unless otherwise noted.

3-(4-tolyl)pyridine

(117) ##STR00080##

(118) According to the general procedure, a mixture of 3-chloropyridine (95 μL, 1.00 mmol), p-tolylboronic acid (204 mg, 1.50 mmol), (π-crotyl)Pd(XPhos)Cl (14 mg, 0.02 mmol), 2 mL THF, and 4 mL of 0.5 M aqueous K.sub.3PO.sub.4 are stirred at room temperature for 2 hours. The crude material is chromatographed on silica gel with a gradient of 10-40% EtOAc/hexanes as the eluent to give 160 mg (0.95 mmol, 95%) of 3-(4-tolyl)pyridine as a colorless solid. The spectroscopic data match those previously reported (C. L. Cioffi, W. T. Spencer, J. J. Richards, R. J. Herr, J. Org. Chem. 2004, 69, 2210).

2-(thiophen-2-yl)quinoline

(119) ##STR00081##

(120) According to the general procedure, a mixture of 2-chloroquinoline (164 mg, 1.00 mmol), 2-thienylboronic acid (192 mg, 1.50 mmol), (π-crotyl)Pd(XPhos)Cl (14 mg, 0.02 mmol), 2 mL THF, and 4 mL of 0.5 M aqueous K.sub.3PO.sub.4 are stirred at 45° C. for 2 hours. The crude material is chromatographed on silica gel with a gradient of 0-5% EtOAc/hexanes as the eluent to give 208 mg (0.99 mmol, 99%) of 2-(thiophen-2-yl)quinoline as a colorless solid. The spectroscopic data match those previously reported (F.-F. Zhuo, W.-W. Xie, Y.-X. Yang, L. Zhang, P. Wang, R. Yuan, C.-S. Da, J. Org. Chem. 2013, 78, 3243).

4-(furan-2-yl)-2, 6-dimethoxypyrimidine

(121) ##STR00082##

(122) According to the general procedure, a mixture of 6-chloro-2,4-dimethoxypyrimidine (175 mg, 1.00 mmol), 2-furanboronic acid (168 mg, 1.50 mmol), (π-crotyl)Pd(XPhos)Cl (14 mg, 0.02 mmol), 2 mL THF, and 4 mL of 0.5 M aqueous K.sub.3PO.sub.4 are stirred at room temperature for 1 hour. The crude material is chromatographed on silica gel with a gradient of 0-10% EtOAc/hexanes as the eluent to give 194 mg (0.94 mmol, 94%) of 4-(furan-2-yl)-2,6-dimethoxypyrimidine as a colorless solid. .sup.1H NMR (400 MHz, CDCl.sub.3, δ): 7.53 (dd, J=0.9 Hz, 1.9 Hz, 1H), 7.19 (dd, J=0.7 Hz, 3.5 Hz, 1H), 6.69 (s, 1H), 6.53 (dd, J=1.7 Hz, 3.4 Hz, 1H) 4.02 (s, 3H), 3.99 (s, 3H).

(123) .sup.13C NMR (100 MHz, CDCl.sub.3, δ): 172.6, 165.6, 157.4, 152.2, 144.6, 112.3, 111.9, 95.0, 54.8, 54.0. Anal. Calcd. for C.sub.10H.sub.10N.sub.2O.sub.3: C, 58.25; H, 4.89; N, 13.59. Found: C, 58.19; H, 4.72; N, 13.42.

2-(2,6-difluorophenyl)-6-methoxypyridine

(124) ##STR00083##

(125) According to the general procedure, a mixture of 2-chloro-6-methoxypyridine (119 μL, 1.00 mmol), 2,6-difluorophenylboronic acid (237 mg, 1.50 mmol), (π-crotyl)Pd(XPhos)Cl (14 mg, 0.02 mmol), 2 mL THF, and 4 mL of 0.5 M aqueous K.sub.3PO.sub.4 are stirred at room temperature for 30 minutes. The crude material is chromatographed on silica gel with a gradient of 0-5% EtOAc/hexanes as the eluent to give 195 mg (0.88 mmol, 88%) of 2-(2,6-difluorophenyl)-6-methoxypyridine as a pale yellow oil.

(126) .sup.1H NMR (400 MHz, CDCl.sub.3, δ): 7.64 (t, J=7.8 Hz, 1H), 7.35-7.26 (m, 1H), 7.05 (d, J=7.1 Hz, 1H), 7.00-6.92 (m, 2H), 6.75 (d, J=8.3 Hz, 1H), 3.95 (s, 3H).

(127) .sup.13C NMR (100 MHz, CDCl.sub.3, δ): 163.8, 160.5 (dd, J=250.7 Hz, 6.97 Hz), 146.7, 138.6, 129.8 (t, J=10.23 Hz), 118.8 (t, J=1.95 Hz), 118.2 (t, J=17.23 Hz), 111.8 (dd, J=26.1 Hz, 6.6 Hz), 110.3, 53.6. Anal. Calcd. for C.sub.12H.sub.9F.sub.2NO: C, 65.16; H, 4.10; N, 6.33. Found: C, 65.14; H, 4.37; N, 6.46.

5-(dibenzo[b,d]furan-4-yl)-1,3-dimethyl-1H-pyrazole

(128) ##STR00084##

(129) According to the general procedure, a mixture of 5-chloro-1,3-dimethyl-1H-pyrazole (115 μL, 1.00 mmol), dibenzo[b]-furan-4-boronic acid (318 mg, 1.50 mmol), (π-crotyl)Pd(XPhos)Cl (14 mg, 0.02 mmol), 2 mL THF, and 4 mL of 0.5 M aqueous K.sub.3PO.sub.4 are stirred at room temperature for 2 hours. The crude material is chromatographed on silica gel with a gradient of 0-10% EtOAc/hexanes as the eluent to give 240 mg (0.92 mmol, 92%) of 5-(dibenzo[b,d]furan-4-yl)-1,3-dimethyl-1H-pyrazole as an off-white solid.

(130) .sup.1H NMR (400 MHz, CDCl.sub.3, δ): 8.02-7.97 (m, 2H), 7.57 (d, J=8.8 Hz, 1H), 7.58-7.36 (m, 4H), 6.33 (s, 1H), 3.85 (s, 3H), 2.39 (s, 3H).

(131) .sup.13C NMR (100 MHz, CDCl.sub.3, δ): 156.2, 153.3, 147.9, 139.1, 128.0, 127.7, 125.0, 124.0, 123.2, 123.0, 121.1, 120.9, 115.6, 112.0, 107.1, 37.4, 13.7.

(132) Anal. Calcd. for C.sub.17H.sub.14N.sub.2O: C, 77.84; H, 5.38; N, 10.68. Found: C, 77.93; H, 5.29; N, 10.56.

5-methyl-6-(thiophen-3-yl)imidazo[1,2-a]pyridine hydromethanesulfonate

(133) ##STR00085##

(134) According to the general procedure, a mixture of 6-bromo-5-methylimidazo[1,2,a]pyridine (167 mg, 1.00 mmol), 3-thienylboronic acid (152 mg, 1.50 mmol), (π-crotyl)Pd(XPhos)Cl (14 mg, 0.02 mmol), 2 mL THF, and 4 mL of 0.5 M aqueous K.sub.3PO.sub.4 are stirred at 45° C. for 5 hours. The crude material is taken up in 10 mL of isopropyl acetate and stirred. 0.08 mL of methanesulfonic acid is added slowly as a precipitate developed, and the mixture is stirred at rt for 30 minutes. The solid is collected by vacuum filtration, washed (3×5 mL isopropyl acetate, 1×10 mL hexanes), and dried in vacuo to give 194 mg (0.80 mmol, 80%) of 5-methyl-6-(thiophen-3-yl)imidazo[1,2-a]pyridine hydromethanesulfonate as a tan solid.

(135) .sup.1H NMR (400 MHz, 4:1 D.sub.2O/DMSO-d.sub.6, δ): 8.18 (s, 1H), 8.06 (s, 1H), 7.97 (d, J=9.3 Hz, 1H), 7.85 (d, J=9.3 Hz, 1H), 7.70-7.60 (m, 2H), 7.32 (d, J=4.6 Hz, 1H), 2.87-2.77 (m, 6H).

(136) .sup.13C NMR (100 MHz, 4:1 D.sub.2O/DMSO-d.sub.6, δ): 140.4, 137.8, 137.3, 137.2, 130.1, 128.5, 127.3, 126.5, 123.9, 114.7, 110.4, 40.1, 17.4.

(137) HRMS (ESI) m/z [M+H−OMs].sup.+ Calcd. for C.sub.12H.sub.10N.sub.2S: 215.0643. Found: 215.0644.

Example 8 (According to the Invention)

Monoarylation of Ketone Enolates

(138) ##STR00086##

(139) The XPhos complexes (π-allyl)Pd(XPhos)Cl, (π-crotyl)Pd(XPhos)Cl and (π-cinnamyl)Pd(XPhos)Cl were evaluated in the monoarylation of ketone enolates. These complexes all promoted rapid conversion (≥95%) after 1 hour in the α-arylation of acetophenone with 4-chloroanisole (see FIG. 6.). The rate of conversion is significantly lower when G3 XPhos was employed as the precatalyst; 34% conversion is observed at 1 hour, and 4 hours was necessary to reach high conversion (93%). Carbazole is shown to retard the rate of this reaction, albeit to a lesser extent than in amination. The kinetic profile of the reaction catalyzed by (π-allyl)Pd(XPhos)Cl with 1 mol % of carbazole added nearly matched that of the G3 XPhos-catalyzed reaction.

(140) Four examples of ketone enolate arylations using (π-allyl)Pd(XPhos)Cl highlight the versatility of this catalyst:

(141) ##STR00087##

(142) General Procedure for the Ketone Enolate Arylation Reactions

(143) An oven dried Schlenk tube equipped with a Teflon-coated magnetic stir bar is charged with (π-allyl)Pd(XPhos)Cl (1-2 mol %, as indicated), aryl chloride (1.00 mmol, if solid), and KOt-Bu (2.00-2.40 mmol, as indicated). The tube is capped with a rubber septum and was evacuated and backfilled with nitrogen. This evacuation/backfill cycle is repeated two additional times. Dodecane (GC standard, 0.20 mmol), the ketone (1.20 mmol), aryl chloride (1.00 mmol, if liquid), and anhydrous toluene (4 mL) are added sequentially via syringe. The tube is placed in a preheated oil bath (60° C.) and stirred for the indicated time. The tube is then removed from the oil bath and allowed to cool to room temperature. Saturated NH.sub.4Cl (4 mL) and EtOAc (10 mL) are added, and the aqueous phase is extracted with EtOAc (3×10 mL). The organic extracts are combined, dried over anhydrous MgSO.sub.4, filtered, and concentrated in vacuo. The residue is chromatographed on silica gel using a Teledyne ISCO CombiFlashRf.

2-(4-methoxyphenyl)-1-phenylethan-1-one

(144) ##STR00088##

(145) According to the general procedure, a mixture of 4-chloroanisole (123 μL, 1.00 mmol), acetophenone (140 μL, 1.20 mmol), KOtBu (224 mg, 2.00 mmol), (π-allyl)Pd(XPhos)Cl (6.6 mg, 0.01 mmol), and 4 mL of toluene are stirred at 60° C. for 2 hours. The crude material is chromatographed on silica gel with a gradient of 0-4% EtOAc/hexanes as the eluent to give 210 mg (0.93 mmol, 93%) of 2-(4-methoxyphenyl)-1-phenylethan-1-one as a colorless solid. The spectroscopic data match those previously reported (M. R. Biscoe, S. L. Buchwald, Org. Lett. 2009, 11, 1773).

1-(pyridin-3-yl)-2-(quinolin-6-yl)ethan-1-one

(146) ##STR00089##

(147) According to the general procedure, a mixture of 6-chloroquinoline (164 mg, 1.00 mmol), 3-acetylpyridine (132 μL, 1.20 mmol), KOtBu (269 mg, 2.40 mmol), (π-allyl)Pd(XPhos)Cl (6.6 mg, 0.01 mmol), and 4 mL of toluene are stirred at 60° C. for 4 hours. The crude material is chromatographed on silica gel with EtOAc as the eluent to give 236 mg (0.95 mmol, 95%) of 1-(pyridin-3-yl)-2-(quinolin-6-yl)ethan-1-one as a pale yellow solid.

(148) .sup.1H NMR (400 MHz, CDCl.sub.3, δ): 9.29 (s, 1H), 8.90 (d, J=3.5 Hz, 1H), 8.88 (d, J=3.5 Hz, 1H), 8.29 (d, J=8.2 Hz, 1H), 8.17-8.02 (m, 2H), 7.72 (s, 1H), 7.65 (d, J=8.5 Hz, 1H), 7.47-7.31 (m, 2H), 4.50 (s, 2H).

(149) .sup.13C NMR (100 MHz, CDCl.sub.3, δ): 196.1, 153.8, 150.6, 150.1, 147.6, 135.9, 135.8, 132.1, 131.8, 131.2, 130.1, 128.4, 128.2, 123.9, 121.5, 45.7.

(150) HRMS (ESI) m/z [M+H].sup.+ Calcd. for C.sub.16H.sub.13N.sub.2O: 249.1028. Found: 249.1020.

1-(furan-2-yl)-2-(4-(trifluoromethyl)phenyl)ethan-1-one

(151) ##STR00090##

(152) According to the general procedure, a mixture of 4-chlorobenzotrifluoride (133 μL, 1.00 mmol), 2 acetylfuran (132 μL, 1.20 mmol), KOtBu (269 mg, 2.40 mmol), (π-allyl)Pd(XPhos)Cl (13.2 mg, 0.02 mmol), and 4 mL of toluene are stirred at 60° C. for 4 hours. The crude material is chromatographed on silica gel with EtOAc as the eluent to give 236 mg (0.95 mmol, 95%) of 1-(furan-2-yl)-2-(4-(trifluoromethyl)phenyl)ethan-1-one as a pale yellow solid. The spectroscopic data match those previously reported (T. Miura, S. Fujioka, N. Takemura, H. Iwasaki, M. Ozeki, N. Kojima, M. Yamashita, Synthesis, 2014, 46, 496).

1-(naphthalen-1-yl)-2-(pyridin-3-yl)ethan-1-one

(153) ##STR00091##

(154) According to the general procedure, a mixture of 3-chloropyridine (95 μL, 1.00 mmol), 1-acetonaphthalene (182 μL, 1.20 mmol), KOtBu (269 mg, 2.40 mmol), (π-allyl)Pd(XPhos)Cl (13.2 mg, 0.02 mmol), and 4 mL of toluene are stirred at 60° C. for 4 hours. The crude material is chromatographed on silica gel with 50% EtOAc/hexanes as the eluent to give 237 mg (0.96 mmol, 96%) of 1-(naphthalen-1-yl)-2-(pyridin-3-yl)ethan-1-one as a yellow oil.

(155) 1H NMR (400 MHz, CDCl.sub.3, δ): 8.61-8.49 (m, 3H), 8.01-7.94 (m, 2H), 7.89 (dd, J=1.6 Hz, 7.9 Hz, 1H), 7.63 (dt, J=1.8 Hz, 7.8 Hz, 1H), 7.60-7.48 (m, 3H), 7.29-7.23 (m, 1H), 4.38 (s, 2H).

(156) .sup.13C NMR (100 MHz, CDCl.sub.3, δ): 200.3, 150.8, 148.5, 137.2, 135.0, 134.1, 133.4, 130.4 (2 peaks), 128.6, 128.3, 128.2, 126.8, 125.8, 124.4, 123.6, 45.7.

(157) HRMS (ESI) m/z [M+1-1].sup.+ Calcd. for C.sub.17H.sub.14NO: 248.1075. Found: 248.1075.

Example 9 (According to the Invention)

Trifluoromethanation Using (π-allyl)Pd(BrettPhos)Cl

(158) ##STR00092##

(159) In a nitrogen filled glovebox a 2 dram reaction vial equipped with a Teflon-coated magnetic stir bar is charged with (allyl)Pd(BrettPhos)Cl (21.6 mg, 30 μmol), BrettPhos (16.1 mg, 30 μmol), and potassium fluoride (58.1 mg, 1.0 mmol). Dioxane (1.65 mL), triethyl(trifluoromethyl)silane (188 μL, 1.0 mmol), and 1-nbutyl-4-chlorobenzene (84.3 μL, 0.50 mmol) are added via syringe. The reaction vial is capped with an open top cap and PTFE Faced Silicone septum, removed from the glovebox, and placed on a preheated aluminum block (120° C.) and stirred vigorously for 16 hours. After cooling to room temperature the vial is opened to air and an aliquot (˜200 μL) is removed, passed through a plug of Celite, eluted with ethyl acetate (2 mL) and analyzed by GC. The benzotrifluoride product is observed in 84% GC yield (uncalibrated).

(160) This experiment demonstrates that the precatalyst (π-allyl)Pd(BrettPhos)Cl is competent in the trifluoromethanation of 4-n-butyl-1-chlorobenzene.

(161) Further aspects and embodiments of the present disclosure are set out in the following numbered clauses: 1. A palladium(II) complex of formula (1):

(162) ##STR00093## wherein: R.sub.1 and R.sub.2 are independently organic groups having 1-20 carbon atoms, or R.sub.1 and R.sub.2 are linked to form a ring structure with E; R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are independently —H or organic groups having 1-20 carbon atoms; or R.sub.1/R.sub.3 or R.sub.2/R.sub.3 forms a ring structure with the atoms to which they are attached and in this instance R.sub.4/R.sub.5, R.sub.5/R.sub.6, R.sub.7/R.sub.8, R.sub.8/R.sub.9, R.sub.9/R.sub.10 or R.sub.10/R.sub.11 may independently form a ring structure with the carbon atoms to which they are attached or R.sub.1, R.sub.2, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are as defined above; R.sub.12 is an organic group having 1-20 carbon atoms; m is 0, 1, 2, 3, 4 or 5; E is P or As; and X is a coordinating anionic ligand;
provided that the palladium complex of formula (1) is not (π-crotyl)PdCl(dicyclohexylphosphino-2-biphenyl). 2. A palladium(II) complex according to clause 1, wherein E is P. 3. A palladium(II) complex according to clause 2, wherein R.sub.1 and R.sub.2 are more sterically bulky than a cyclohexyl group when R.sub.7, R.sub.8, R.sub.9, R.sub.10 and/or R.sub.11 are less sterically bulky than a cyclohexyl group. 4. A palladium(II) complex according to clause 2, wherein R.sub.1 and R.sub.2 are less sterically bulky than a cyclohexyl group when R.sub.7, R.sub.8, R.sub.9, R.sub.10 and/or R.sub.11 are more sterically bulky than a cyclohexyl group. 5. A palladium(II) complex according to any one of the preceding clauses, wherein R.sub.1 and R.sub.2 are independently selected from the group consisting of substituted and unsubstituted straight-chain alkyl, substituted and unsubstituted branched-chain alkyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aryl, and substituted and unsubstituted heteroaryl wherein the heteroatoms are independently selected from sulfur, nitrogen and oxygen. 6. A palladium(II) complex according to any one of the preceding clauses, wherein R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are independently selected from the group consisting of —H, substituted and unsubstituted straight-chain alkyl, substituted and unsubstituted branched-chain alkyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted alkoxy, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, substituted and unsubstituted —N(alkyl).sub.2 (wherein the alkyl groups may be the same or different and are independently selected from straight-chain or branched-chain groups), substituted and unsubstituted —N(cycloalkyl).sub.2 (wherein the cycloalkyl groups may be the same or different), substituted and unsubstituted —N(aryl).sub.2 (wherein the aryl groups may be the same or different), substituted and unsubstituted —N(heteroaryl).sub.2 (wherein the heteroaryl groups may be the same or different) and substituted and unsubstituted heterocycloalkyl groups. 7. A palladium(II) complex according to clause 6, wherein each of R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are —H. 8. A palladium(II) complex according to clause 6, wherein two of R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are —H, and the other two of R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are independently selected from the group consisting of unsubstituted straight-chain alkyl, unsubstituted branched-chain alkyl, unsubstituted cycloalkyl and unsubstituted alkoxy. 9. A palladium(II) complex according to any one of the preceding clauses, wherein R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are independently selected from the group consisting of —H, substituted and unsubstituted straight-chain alkyl, substituted and unsubstituted branched-chain alkyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted alkoxy, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, substituted and unsubstituted —N(alkyl).sub.2 (wherein the alkyl groups may be the same or different and are independently selected from straight-chain or branched-chain groups), substituted and unsubstituted —N(cycloalkyl).sub.2 (wherein the cycloalkyl groups may be the same or different), substituted and unsubstituted —N(aryl).sub.2 (wherein the aryl groups may be the same or different), substituted and unsubstituted —N(heteroaryl).sub.2 (wherein the heteroaryl groups may be the same or different) and substituted and unsubstituted heterocycloalkyl groups. 10. A palladium(II) complex according to clause 9, wherein each of R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are —H. 11. A palladium(II) complex according to clause 9, wherein three of R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are —H, and the other two of R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are independently selected from the group consisting of unsubstituted straight-chain alkyl, unsubstituted branched-chain alkyl, unsubstituted cycloalkyl, unsubstituted alkoxy, unsubstituted —N(alkyl).sub.2 (wherein the alkyl groups may be the same or different and may be independently selected from straight-chain or branched-chain groups) and unsubstituted —N(aryl).sub.2 (wherein the aryl groups may be the same or different). 12. A palladium(II) complex according to clause 9, wherein two of R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are —H, and the other three of R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are independently selected from the group consisting of unsubstituted straight-chain alkyl, unsubstituted branched-chain alkyl, unsubstituted cycloalkyl, unsubstituted alkoxy, unsubstituted —N(alkyl).sub.2 (wherein the alkyl groups may be the same or different and may be independently selected from straight-chain or branched-chain groups) and unsubstituted —N(aryl).sub.2 (wherein the aryl groups may be the same or different). 13. A palladium(II) complex according to any one of preceding clauses, wherein the monodentate tertiary phosphine ligand is selected from the group consisting of:

(163) ##STR00094## 14. A palladium(II) complex according to any one of the preceding clauses, wherein R.sub.12 is selected from the group consisting of substituted and unsubstituted straight-chain alkyl, substituted and unsubstituted branched-chain alkyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted aryl, and substituted and unsubstituted heteroaryl wherein the heteroatoms are independently selected from sulfur, nitrogen and oxygen. 15. A palladium(II) complex according to any one of the preceding clauses, wherein X is a halo group or a trifluoroacetate group. 16. A palladium(II) complex according to any one of the preceding clauses, wherein the complex of formula (1) is selected from the group consisting of:

(164) ##STR00095## ##STR00096## ##STR00097## 17. A palladium complex of formula (2);

(165) ##STR00098## wherein: R.sub.18 and R.sub.19 are independently selected from the group consisting of -Me, -Et, —.sup.nPr, —.sup.iPr, —.sup.nBu, —.sup.iBu, cyclohexyl and cycloheptyl; R.sub.12 is an organic group having 1-20 carbon atoms; R.sub.20, R.sub.21, R.sub.22, R.sub.23 and R.sub.24 are independently —H or organic groups having 1-20 carbon atoms; or one or both pairs selected from R.sub.20/R.sub.21 or R.sub.22/R.sub.23 may independently form a ring structure with the atoms to which they are attached; m is 0, 1, 2, 3, 4 or 5; and X is a coordinating anionic ligand. 18. A palladium(II) complex according to clause 17, wherein R.sub.18 and R.sub.19 are the same and are cyclohexyl groups. 19. A palladium(II) complex according to clause 17 or clause 18, wherein R.sub.20 and R.sub.21 are independently selected from the group consisting of —H, substituted and unsubstituted straight-chain alkyl, substituted and unsubstituted branched-chain alkyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted alkoxy, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, substituted and unsubstituted —N(alkyl).sub.2 (wherein the alkyl groups may be the same or different and are independently selected from straight-chain or branched-chain groups), substituted and unsubstituted —N(cycloalkyl).sub.2 (wherein the cycloalkyl groups may be the same or different), substituted and unsubstituted —N(aryl).sub.2 (wherein the aryl groups may be the same or different), substituted and unsubstituted —N(heteroaryl).sub.2 (wherein the heteroaryl groups may be the same or different) and substituted and unsubstituted heterocycloalkyl groups. 20. A palladium(II) complex according to clause 19, wherein both of R.sub.20 and R.sub.21 are —H. 21. A palladium(II) complex according to any one of clauses 17 to 20, wherein R.sub.22 and R.sub.24 are independently selected from the group consisting of —H, substituted and unsubstituted straight-chain alkyl, substituted and unsubstituted branched-chain alkyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted alkoxy, substituted and unsubstituted-thioalkyl, substituted and unsubstituted aryl, substituted and unsubstituted heteroaryl, substituted and unsubstituted —N(alkyl).sub.2 (wherein the alkyl groups may be the same or different and are independently selected from straight-chain or branched-chain groups), substituted and unsubstituted —N(cycloalkyl).sub.2 (wherein the cycloalkyl groups may be the same or different), substituted and unsubstituted —N(aryl).sub.2 (wherein the aryl groups may be the same or different), substituted and unsubstituted —N(heteroaryl).sub.2 (wherein the heteroaryl groups may be the same or different). 22. A palladium(II) complex according to any one of clauses 17 to 21, wherein R.sub.23 is selected from the group consisting of —H, substituted and unsubstituted straight-chain alkyl, substituted and unsubstituted branched-chain alkyl, substituted and unsubstituted cycloalkyl, substituted and unsubstituted alkoxy, substituted and unsubstituted aryl, and substituted and unsubstituted heteroaryl. 23. A palladium(II) complex according to any one of clauses 17 to 22, wherein each of R.sub.22, R.sub.23 and R.sub.24 are phenyl groups. 24. A palladium(II) complex according to any one of clauses 17 to 23, wherein the complex of formula (2) is selected from the group consisting of:

(166) ##STR00099## 25. A process for the preparation of a complex of formula (1) or a complex of formula (2), the process comprising the step of reacting a complex of formula (3) with a monodentate biaryl ligand of formula (4) or a monodentate bi-heteroaryl tertiary phosphine ligand of formula (5) to form the complex of formula (1) or the complex of formula (2),

(167) ##STR00100## wherein, R.sub.1 and R.sub.2 are independently organic groups having 1-20 carbon atoms, or R.sub.1 and R.sub.2 are linked to form a ring structure with E; R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are independently —H or organic groups having 1-20 carbon atoms; or one or more pairs selected from R.sub.1/R.sub.3, R.sub.2/R.sub.3, R.sub.3/R.sub.4, R.sub.4/R.sub.5, R.sub.5/R.sub.6, R.sub.7/R.sub.8, R.sub.8/R.sub.9, R.sub.9/R.sub.10 or R.sub.10/R.sub.11 independently may form a ring structure with the carbon atoms to which they are attached; R.sub.12 is an organic group having 1-20 carbon atoms; R.sub.18 and R.sub.19 are independently selected from the group consisting of -Me, -Et, —.sup.nPr, —.sup.iPr, —.sup.nBu, —.sup.iBu, cyclohexyl and cycloheptyl; R.sub.20, R.sub.21, R.sub.22, R.sub.23 and R.sub.24 are independently —H or organic groups having 1-20 carbon atoms; or one or both pairs selected from R.sub.20/R.sub.21 or R.sub.22/R.sub.23 independently may form a ring structure with the atoms to which they are attached; m is 0, 1, 2, 3, 4 or 5; E is P or As; and X is a coordinating anionic ligand; provided that the palladium complex of formula (1) is not (π-crotyl)PdCl(dicyclohexylphosphino-2-biphenyl). 26. A process for carrying out a carbon-carbon coupling reaction in the presence of a catalyst, the process comprising: (a) the use of a complex of formula (1):

(168) ##STR00101## wherein: R.sub.1 and R.sub.2 are independently organic groups having 1-20 carbon atoms, or R.sub.1 and R.sub.2 are linked to form a ring structure with E; R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are independently —H or organic groups having 1-20 carbon atoms; or R.sub.1/R.sub.3 or R.sub.2/R.sub.3 forms a ring structure with the atoms to which they are attached and in this instance R.sub.4/R.sub.5, R.sub.5/R.sub.6, R.sub.7/R.sub.8, R.sub.8/R.sub.9, R.sub.9/R.sub.10 or R.sub.10/R.sub.11 may independently form a ring structure with the carbon atoms to which they are attached or R.sub.1, R.sub.2, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are as defined above; R.sub.12 is an organic group having 1-20 carbon atoms; m is 0, 1, 2, 3, 4 or 5; E is P or As; and X is a coordinating anionic ligand; or: (b) a complex of formula (2) as defined in any one of clauses 17 to 24. 27. A process according to clause 26, the process comprising the use of a complex of formula (1) as defined in any one of clauses 1 to 16. 28. A process according to clause 26, the process comprising the use of the complex of formula (2) as defined in any one of clauses 17 to 24. 29. A process for carrying out a carbon-heteroatom coupling reaction in the presence of a catalyst, the process comprising: (a) the use of a complex of formula (1):

(169) ##STR00102## wherein: R.sub.1 and R.sub.2 are independently organic groups having 1-20 carbon atoms, or R.sub.1 and R.sub.2 are linked to form a ring structure with E; R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are independently —H or organic groups having 1-20 carbon atoms; or R.sub.1/R.sub.3 or R.sub.2/R.sub.3 forms a ring structure with the atoms to which they are attached and in this instance R.sub.4/R.sub.5, R.sub.5/R.sub.6, R.sub.7/R.sub.8, R.sub.8/R.sub.9, R.sub.9/R.sub.10 or R.sub.10/R.sub.11 may independently form a ring structure with the carbon atoms to which they are attached or R.sub.1, R.sub.2, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are as defined above; R.sub.12 is an organic group having 1-20 carbon atoms; m is 0, 1, 2, 3, 4 or 5; E is P or As; and X is a coordinating anionic ligand; or: (b) a complex of formula (2) as defined in any one of clauses 17 to 24. 30. A process according to clause 29, the process comprising the use of a complex of formula (1) as defined in any one of clauses 1 to 16. 31. A process according to clause 29, the process comprising the use of the complex of formula (2) as defined in any one of clauses 17 to 24. 32. The use of a complex of formula (1) or a complex of formula (2) as a catalyst in carbon-carbon coupling reactions, wherein: (a) the complex of formula (1) is:

(170) ##STR00103## wherein: R.sub.1 and R.sub.2 are independently organic groups having 1-20 carbon atoms, or R.sub.1 and R.sub.2 are linked to form a ring structure with E; R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are independently —H or organic groups having 1-20 carbon atoms; or R.sub.1/R.sub.3 or R.sub.2/R.sub.3 forms a ring structure with the atoms to which they are attached and in this instance R.sub.4/R.sub.5, R.sub.5/R.sub.6, R.sub.7/R.sub.8, R.sub.8/R.sub.9, R.sub.9/R.sub.10 or R.sub.10/R.sub.11 may independently form a ring structure with the carbon atoms to which they are attached or R.sub.1, R.sub.2, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are as defined above; R.sub.12 is an organic group having 1-20 carbon atoms; m is 0, 1, 2, 3, 4 or 5; E is P or As; and X is a coordinating anionic ligand; and: (b) the complex of formula (2) as defined in any one of clauses 17 to 24. 33. The use according to clause 32, wherein the complex of formula (1) is as defined in any one of clauses 1 to 16. 34. The use according to clause 32, wherein the complex of formula (2) is as defined in any one of clauses 17 to 24. 35. The use of a complex of formula (1) or a complex of formula (2) as a catalyst in carbon-heteroatom coupling reactions, wherein: (a) the complex of formula (1) is:

(171) ##STR00104## wherein: R.sub.1 and R.sub.2 are independently organic groups having 1-20 carbon atoms, or R.sub.1 and R.sub.2 are linked to form a ring structure with E; R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are independently —H or organic groups having 1-20 carbon atoms; or R.sub.1/R.sub.3 or R.sub.2/R.sub.3 forms a ring structure with the atoms to which they are attached and in this instance R.sub.4/R.sub.5, R.sub.5/R.sub.6, R.sub.7/R.sub.8, R.sub.8/R.sub.9, R.sub.9/R.sub.10 or R.sub.10/R.sub.11 may independently form a ring structure with the carbon atoms to which they are attached or R.sub.1, R.sub.2, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are as defined above; R.sub.12 is an organic group having 1-20 carbon atoms; m is 0, 1, 2, 3, 4 or 5; E is P or As; and X is a coordinating anionic ligand; and: (b) the complex of formula (2) is as defined in any one of clauses 17 to 24. 36. The use according to clause 35, wherein the complex of formula (1) is as defined in any one of clauses 1 to 16. 37. The use according to clause 35, wherein the complex of formula (2) is as defined in any one of clauses 17 to 24.