Triaryl phosphine ligands, preparation method therefor, and use in catalysing coupling reactions
11420987 · 2022-08-23
Assignee
Inventors
Cpc classification
B01J2540/40
PERFORMING OPERATIONS; TRANSPORTING
B01J2231/4283
PERFORMING OPERATIONS; TRANSPORTING
B01J2540/10
PERFORMING OPERATIONS; TRANSPORTING
C07C217/84
CHEMISTRY; METALLURGY
C07F9/655345
CHEMISTRY; METALLURGY
C07C209/10
CHEMISTRY; METALLURGY
B01J31/2404
PERFORMING OPERATIONS; TRANSPORTING
B01J2231/4211
PERFORMING OPERATIONS; TRANSPORTING
C07C213/02
CHEMISTRY; METALLURGY
B01J2531/0288
PERFORMING OPERATIONS; TRANSPORTING
B01J2540/225
PERFORMING OPERATIONS; TRANSPORTING
B01J2540/30
PERFORMING OPERATIONS; TRANSPORTING
International classification
B01J31/00
PERFORMING OPERATIONS; TRANSPORTING
B01J31/24
PERFORMING OPERATIONS; TRANSPORTING
C07F15/00
CHEMISTRY; METALLURGY
Abstract
Provided are triaryl phosphine ligands, as shown in general formulae Ia and Ib, or a mixture thereof, and a preparation method therefor. The invention addresses the deficiencies of biaryl phosphine ligands invented by Buchwald et al. Also provided are a triaryl phosphine coordinated palladium complex, a system composed of triaryl phosphine ligand and a palladium salt or complex, and a use of the triaryl phosphine coordinated palladium complex in catalysing organic reactions, in particular a use in catalysis of coupling reactions involving (pseudo)halogenated aromatic hydrocarbon as substrate.
Claims
1. Triaryl phosphine ligands are elected from the group consisting of the following specific phosphine compounds: [2,6-Bis(2,6-dimethylphenyl)phenyl]-diphenylphosphine; [2,6-Bis(2,6-dimethylphenyl)phenyl]-dicyclohexylphosphine; [2,6-Bis(2,6-dimethylphenyl)phenyl]-cyclohoxyl-2-thienylphosphine; [2,6-Bis(2,6-dimethylphenyl)phenyl]-tert-butyl-2-furylphosphine; [2,6-Bis(2,4,6-trimethylphenyl)phenyl]-[2-dimethylaminophenyl]-phenylphosphine; [2,6-Bis(2,4,6-trimethylphenyl)phenyl]-[2-dimethylaminophenyl]-cyclohexylphosphine; [2,6-Bis(2,4,6-trimethylphenyl)phenyl]-[2-dimethylaminophenyl]-tert-butylphosphine; [2,6-Bis(2,6-diisopropylphenyl)phenyl]-dicyclohexylphosphine; [2,6-Bis(2,6-diisopropylphenyl)phenyl]-phenyl-cyclohexylphosphine; [2,6-Bis(2,6-diisopropylphenyl)phenyl]-methyl-tert-butylphosphine; [2,6-Bis(2,6-diisopropylphenyl)phenyl]-phenyl-isopropylphosphine; [2,6-Bis(2,6-diisopropylphenyl)phenyl]-[2′,6′-dimethyl-2-biphenyl]-methylphosphine; [2,6-Bis(2,6-diisopropylphenyl)phenyl]-[2′,6′-dimethoxy-2-biphenyl]-methylphosphine; [2,6-Bis(2,6-diisopropylphenyl)phenyl]-[2′,6′-dimethoxy-2-biphenyl]-cyclohexylphosphine; [2,6-Bis(2,6-diisopropylphenyl)phenyl]-[2′,6′-diisopropyl-2-biphenyl]-cyclohexylphosphine; [2,6-Bis(2,4,6-triisopropylphenyl)phenyl]-dicyclohexylphosphine; [2,6-Bis(2,4,6-triisopropylphenyl)phenyl]-phenyl-cyclohexylphosphine; [2,6-Bis(2,4,6-triisopropylphenyl)phenyl]-methyl-tert-butylphosphine; [2,6-Bis(2,4,6-triisopropylphenyl)phenyl]-cyclohexyl-isopropylphosphine; [2,6-Bis(2,4,6-triisopropylphenyl)phenyl]-[2′,6′-dimethyl-2-biphenyl]-n-butylphosphine; [2,6-Bis(2,4,6-triisopropylphenyl)phenyl]-[2′,6′-dimethoxy-2-biphenyl]-methylphosphine; [2,6-Bis(2,4,6-triisopropylphenyl)phenyl]-[2′,6′-dimethoxy-2-biphenyl]-cyclohexylphosphine; [2,6-Bis(2,4,6-triisopropylphenyl)phenyl]-[2′,6′-diisopropyl-2-biphenyl]-tert-butylphosphine.
Description
EXEMPLIFICATION
(1) The following examples illustrate specific embodiments of the invention, but don't mean that the invention is limited to the following examples.
Definitions
(2) The term “THF” is art-recognized and refers to tetrahydrofuran.
(3) The term “TMEDA” is art-recognized and refers to N,N,N′,N′-tetramethylethylenediamine.
(4) Preparation method of Grignard reagent. To an oven-dried 100 mL three-necked flask, equipped with a stir bar, a condenser tube, a constant pressure funnel and a suction connector, and add magnesium in an inert atmosphere. The mixture of THE and bromine aromatic hydrocarbon are placed in a constant pressure funnel, and about 1 mL is first added into the three-necked flask. After the reaction is initiated, the remaining mixture is dropped into the three-necked flask (about 15 min) while maintaining a slight boiling. React in an oil bath at 70° C. for 2 to 5 h, then cool to room temperature for later use.
Example 1. (2,6-Diphenyl-4-methylphenyl)-diphenylphosphine
(5) ##STR00008##
Example 1-1
(6) To an oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, was charged with magnesium (0.29 g, 12.0 mmol), THE (10 mL) and bromobenzene (1.73 g, 11.0 mmol) heated to reflux for 2 h to obtain a Grignard reagent.
(7) To another oven-dried two-neck 250 mL flask was added THE (15 mL) and 3,5-dichlorotoluene (0.81 g, 5.0 mmol), n-butyllithium (2.4 mL of a 2.5 M solution in hexanes, 6.0 mmol) was added dropwise at −78° C. and stirred for 30 min. At that point the Grignard reagent was transferred via cannula to the solution, then warmed to room temperature, and the reaction solution was heated to 80° C. for 6 h. Cooled to −78° C. again, then Ph.sub.2PCl (1.32 g, 6.0 mmol) was added dropwise via cannula and the solution was warmed to room temperature for 6 h. The solvent was a removed in vacuum and 50 mL of brine was added, and the mixture was extract with dichloromethane three times (3×40 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuum. The residue was purified by column chromatography to give 1.39 g of 2,6-bisphenyl-4-methylphenyl-diphenylphosphine as a white crystalline material, 65% yield. m.p.: 144.3-145.9° C.
(8) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.14 (d, J=2.7 Hz, 3H), 7.13 (s, 1H), 7.12-7.07 (m, 10H), 7.06 (t, J=4.3 Hz, 8H), 2.46 (s, 3H).
(9) .sup.13C NMR (101 MHz, CDCl.sub.3) δ: 150.29, 150.13, 143.10, 143.05, 138.80, 137.65, 137.53, 132.45, 132.26, 131.70, 131.66, 129.24, 129.22, 127.65, 127.59, 127.31, 127.00, 126.46, 21.12.
(10) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: −6.85.
(11) HR-MS m/z (%): Calcd for C.sub.31H.sub.25P [M] 428.1688; Found 428.1671 (100).
Example 1-2
(12) To an oven-dried 100 mL flask, equipped with a magnetic stir bar and a condenser, was charged with 2,6-diphenyl-4-methyliodobenzene (0.74 g, 2.0 mmol) and THE (3.0 mL) under nitrogen atmosphere. Cooled to −78° C., 0.89 mL n-butyllithium (2.7 M solution in hexanes, 2.4 mmol) was added dropwise in about 8 min, and the solution was reacted for 2 h. Then Ph.sub.2PCl (0.44 g, 2.0 mmol) was added dropwise via cannula and the solution was warmed to room temperature for 6 h. The solvent was a removed in vacuum and 20 mL of brine was added, then the mixture was extracted with dichloromethane (3×20 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuum to give a light yellow oil. The residue was purified by column chromatography to give 0.60 g of (2,6-disphenyl-4-methylphenyl)-diphenylphosphine as a white crystalline material (71% of yield).
Example 1-3
(13) To an oven-dried 50 mL flask, equipped with a magnetic stir bar and a condenser, was charged with magnesium (0.06 g, 2.2 mmol), and THE (5 mL), and 2,6-diphenyl-4-methyliodobenzene (0.74 g, 2.0 mmol) was added and the mixture was heated to reflux for 2 h to obtain a Grignard reagent. Then Ph.sub.2PCl (1.32 g, 6.0 mmol) was added dropwise via cannula at −78° C. and the solution was warmed to room temperature for 6 h. The solvent was a removed in vacuum and 20 mL of brine was added, then the mixture was extracted with dichloromethane three times (3×20 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuum to give a light yellow oil. The residue was purified by column chromatography to give 0.60 g of (2,6-disphenyl-4-methylphenyl)-diphenylphosphine as a white crystalline material, 69% yield.
Example 2. 2,6-Diphenyl-4-methylphenyl-dicyclohexylphosphine
(14) ##STR00009##
(15) To an oven-dried 100 mL flask, equipped with a magnetic stir bar and a condenser, was charged with 2,6-diphenyl-4-methyliodobenzene (1.85 g, 5.0 mmol) and THE (10.0 mL). Cooled to −78° C., 2.04 mL n-butyllithium (2.5 M solution in hexanes, 5.5 mmol) was added dropwise about 8 min, and the reaction solution was reacted for 2 h at −78° C. Then the solution of Cy.sub.2PCl (1.16 g, 5.0 mmol) in THE (3.0 mL) was added dropwise with cannula and the resulted reaction mixture was warmed to room temperature and stirred for 6 h. The solvent was a removed in vacuum and 20 mL of brine was added, then the mixture was extracted with dichloromethane (3×20 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuum to give a light yellow oil. The residue was purified by column chromatography to give 1.21 g of 2,6-diphenyl-4-methylphenyl-dicyclohexylphosphine as a white crystalline material, 55% yield. m.p.: 138.3-139.6° C.
(16) .sup.1H NMR (500 MHz, CDCl.sub.3) δ: 7.41 (s, 6H), 7.31 (s, 4H), 7.06-7.02 (m, 2H), 2.39 (s, 3H), 1.31 (s, 22H).
(17) .sup.13C NMR (126 MHz, CDCl.sub.3) δ: 144.44, 144.40, 137.22, 131.20, 131.18, 129.89, 129.87, 127.22, 126.61, 35.80, 35.69, 32.91, 32.71, 31.96, 31.53, 31.45, 29.72, 29.68, 29.39, 27.06, 26.99, 26.97, 26.86, 26.26, 22.71, 20.90, 14.13.
(18) .sup.31P NMR (202 MHz, CDCl.sub.3) δ: −0.53.
(19) HR-MS m/z (%): Calcd for C.sub.31H.sub.38P [M.sup.++H] 441.2705; Found 441.2734 (100).
Example 3. 2,6-Bis(2-methylphenyl)phenyl-diphenylphosphine
(20) ##STR00010##
(21) To an oven-dried 100 mL flask, equipped with a magnetic stir bar and a condenser, was charged with 2,6-bis(2-methylphenyl)iodobenzene ((1.54 g, 4.0 mmol) and THF (4.0 mL). Cooled to −78° C. 6.8 mL t-butyllithium (1.3 M solution in hexanes, 8.8 mmol) was added dropwise about 8 min, and the reaction solution was reacted for 2 h. To another oven-dried 100 mL flask, equipped with a magnetic stir bar and a condenser, was charged with CuCl (0.48 g, 4.8 mmol), the lithium reagent was transferred via cannula to the flask was stirred for 20 min. Then Ph.sub.2PCl (0.88 g, 4.0 mmol) was added dropwise via cannula at −78° C. and the solution was warmed to room temperature for 6 h. 40 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 0.91 g of 2,6-bis(2-methylphenyl)phenyl-diphenylphosphine as a white crystalline material (52% yield). m.p.: 146.5-147.3° C.
(22) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.49 (dd, J=14.6, 7.0 Hz, 1H), 7.22-6.70 (m, 20H), 1.92 (d, J=30.1 Hz, 6H).
(23) .sup.13C NMR (101 MHz, CDCl.sub.3) δ: 149.02, 148.85, 142.06, 135.30, 132.86, 132.66, 130.33, 130.29, 129.48, 129.24, 129.22, 129.10, 127.42, 127.35, 127.22, 127.06, 124.55, 20.82, 1.05.
(24) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: −5.37, −7.65.
(25) HR-MS m/z (%): Calcd for C.sub.32H.sub.28P [M.sup.++H] 443.1923; Found 443.1903 (100).
Example 4. 2,6-Bis(2,6-dimethylphenyl)phenyl-diphenylphosphine
(26) ##STR00011##
Example 4-1
(27) To an oven-dried 100 mL flask, equipped with a magnetic stir bar and a condenser, and charged with magnesium (0.61 g, 25.0 mmol), ca. 1 mL of a solution of 2,6-dimethylbromobenzene (4.44 g, 24.0 mmol) in THE (10.0 mL) was added and heated. After the reaction was initiated, the rest 2,6-dimethylbromobenzene solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain the Grignard reagent.
(28) To another oven-dried two-neck 250 mL flask was added THE (15 mL) and 1,3-dichlorobenzene (1.47 g, 10.0 mmol), n-butyllithium (4.8 mL of a 2.5 M solution in hexanes, 12.0 mmol) was added dropwise at −78° C. and stirred for 2 h. At that point the Grignard reagent was transferred via cannula to the solution, then warmed to room temperature, and the reaction solution was heated to 80° C. for 6 h. To the third oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, was charged with CuCl (1.20 g, 12.0 mmol), the above prepared reaction mixture was transferred via cannula and the mixture was a stirred for 20 min. Then Ph.sub.2PCl (2.64 g, 12 mmol) was added dropwise via cannula and the solution was heated to 80° C. for 6 h. Cooled to room temperature, 40 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 2.91 g of 2,6-bis(2,6-dimethylphenyl)phenyl-diphenylphosphine as a white crystalline material, 62% yield. m.p.: 149.5-150.9° C.
(29) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.51 (t, J=7.6 Hz, 1H), 7.16-7.06 (m, 8H), 7.05-6.99 (m, 4H), 6.99-6.92 (m, 2H), 6.82 (d, J=7.6 Hz, 4H), 2.05 (s, 12H).
(30) .sup.13C NMR (101 MHz, CDCl.sub.3) δ: 147.15, 147.00, 141.32, 141.28, 136.72, 136.60, 136.00, 135.99, 134.71, 134.48, 130.39, 130.36, 129.16, 127.92, 127.32, 127.23, 127.18, 21.55, 21.52.
(31) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: −2.18.
(32) HR-MS m/z (%): Calcd for C.sub.34H.sub.32P [M.sup.++H] 471.2251; Found 471.2239 (100).
Example 4-2
(33) To an oven-dried 100 mL flask, equipped with a magnetic stir bar and a condenser, was charged with 2,6-bis(2,6-dimethylphenyl)iodobenzene (1.24 g, 3.0 mmol) and THE (5.0 mL). Cooled to −78° C. 5.1 mL t-butyllithium (1.3 M solution in hexanes, 6.6 mmol) was added dropwise about 8 min, and the reaction solution was reacted for 2 h. To another oven-dried 100 mL flask, equipped with a magnetic stir bar and a condenser, was charged with CuCl (0.48 g, 4.8 mmol), the reaction mixture was transferred via cannula to the flask was stirred for 20 min. Then Ph.sub.2PCl (0.99 g, 4.5 mmol) was added dropwise via cannula at −78° C. and the solution was warmed to room temperature for 6 h. 40 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 0.90 g of 2,6-bis(2,6-dimethylphenyl)phenyl-diphenylphosphine as a white crystalline material(64% yield).
Example 5. [2,6-Bis(2,6-dimethylphenyl)phenyl]-2-thienylcyclohexylphosphine
(34) ##STR00012##
(35) To an oven-dried 100 mL flask, equipped with a magnetic stir bar and a condenser, and charged with magnesium (0.61 g, 25.0 mmol), ca. 1 mL of a solution of 2,6-dimethylbromobenzene (4.44 g, 24.0 mmol) in THE (10.0 mL) was added and heated. After the reaction was initiated, the rest 2,6-dimethylbromobenzene solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent.
(36) To another oven-dried two-neck 250 mL flask was added THE (15 mL) and 1,3-dichlorobenzene (1.47 g, 10.0 mmol), n-butyllithium (4.8 mL of a 2.5 M solution in hexanes, 12.0 mmol) was added dropwise at −78° C. and stirred for 2 h. At that point the Grignard reagent prepared was transferred via cannula to the solution, then warmed to room temperature, and the reaction solution was heated to 80° C. for 6 h, and cooled to room temperature. To a third oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with CuCl (1.19 g, 12.0 mmol), the above reaction solution was transferred via cannula and the mixture was a stirred for 20 min, then a mixture of CyPCl.sub.2 (2.22 g, 12.0 mmol) and THE (10.0 mL) was added dropwise via cannula and the solution was heated to 40° C. for 6 h. The magnesium 2-thienyl bromide (36.0 mmol) was added in −80° C. and the solution was heated to 70° C. for 12 h. 40 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 2.45 g of [2,6-bis(2,6-dimethylphenyl)phenyl-2-thienylcyclohexylphosphine as an orange crystalline material (48% yield). m.p.: 149.9-151.6° C.
(37) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.60-7.52 (m, 1H), 7.49-7.44 (m, 1H), 7.40-7.32 (m, 2H), 7.31-7.25 (m, 2H), 7.12-6.99 (m, 4H), 6.85-6.78 (m, 1H), 6.02-5.94 (m, 1H), 2.42-2.27 (m, 1H), 2.20 (s, 6H), 1.81-1.74 (m, 1H), 1.69 (s, 6H), 1.66-1.58 (m, 3H), 1.56-1.46 (m, 2H), 1.38-1.29 (m, 1H), 1.27-1.18 (m, 1H), 1.15-1.00 (m, 2H).
(38) .sup.13C NMR (101 MHz, CDCl.sub.3) δ: 148.63, 148.49, 139.81, 139.74, 137.22, 136.47, 136.43, 134.82, 132.62, 132.55, 131.87, 131.85, 131.18, 131.11, 128.99, 128.58, 128.49, 128.19, 128.11, 127.54, 127.17, 126.90, 126.56, 34.87, 34.58, 31.67, 31.57, 30.21, 30.13, 26.39, 26.23, 26.19, 26.03, 25.45, 21.50, 20.76.
(39) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: −13.70.
Example 6. [2,6-Bis(2,4,6-trimethylphenyl)phenyl]-[2-dimethylaminophenyl]-phenylphosphine
(40) ##STR00013##
(41) To an oven-dried 100 mL flask, equipped with a magnetic stir bar and a condenser, and charged with magnesium (0.61 g, 25.0 mmol), ca. 1 mL of a solution of 2,4,6-trimethylbromobenzene (4.78 g, 24.0 mmol) in THE (10.0 mL) was added and heated. After the reaction was initiated, the rest 2,4,6-trimethylbromobenzene solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent.
(42) To another oven-dried two-neck 250 mL flask with THE (15 mL) and 1,3-dichlorobenzene (1.47 g, 10.0 mmol), n-butyllithium (4.8 mL of a 2.5 M solution in hexanes, 12.0 mmol) was added dropwise at −78° C. and stirred for 2 h. At that point the Grignard reagent was transferred via cannula to the solution, then warmed to room temperature, and the reaction solution was heated to 80° C. for 6 h and then cooled to room temperature. To a third oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, was charged with CuCl (1.20 g, 12.0 mmol), the above reaction solution was transferred via cannula and the mixture was a stirred for 20 min. A mixture of PhPCl.sub.2 (2.15 g, 12.0 mmol) and THE (10.0 mL) was added dropwise via cannula and the solution was heated to 40° C. for 6 h. The magnesium 2-dimethylaminophenyl bromide (30.0 mmol) was added in −80° C. and the solution was heated to 70° C. for 12 h. 40 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 3.08 g of [2,6-bis(2,4,6-trimethylphenyl)phenyl]-[2-dimethylaminophenyl]-phenylphosphine as an orange crystalline material (57% yield). m.p.: 151.2-152.9° C.
(43) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.62-7.47 (m, 2H), 7.46-7.30 (m, 2H), 7.26-7.17 (m, 2H), 7.09-6.96 (m, 4H), 6.94-6.86 (m, 2H), 6.85-6.75 (m, 2H), 6.39-6.24 (m, 2H), 2.39 (s, 9H), 2.16 (s, 9H), 1.51 (s, 6H).
(44) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: −19.14.
(45) HR-MS m/z (%): Calcd for C.sub.38H.sub.41NP [M.sup.++H] 542.2971; Found 542.2975(100).
Example 7. [2,6-bis(2-methoxyphenyl)phenyl]-diphenylphosphine
(46) ##STR00014##
(47) To an oven-dried 100 mL flask, equipped with a magnetic stir bar and a condenser, was charged with 2,6-bis(2-methoxylphenyl)-iodobenzene (0.83 g, 2.0 mmol) and TH (5.0 mL). Cooled to −78° C., 3.4 mL t-butyllithium (1.3 M solution in hexanes, 4.4 mmol) was added dropwise about 8 min, and the reaction solution was reacted for 2 h. Then Ph.sub.2PCl (0.44 g, 2.0 mmol) was added dropwise via cannula at −78° C. and the solution was warmed to room temperature for 6 h. The solvent was a removed in vacuum and 20 mL of brine was added, then the mixture was extracted with dichloromethane (3×20 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuum to give a light yellow oil. The residue was purified by column chromatography to give 0.76 g of [2,6-bis(2-methoxyphenyl)phenyl]-diphenylphosphine as a white crystalline material, 80% yield. m.p.: 144.6-146.1° C.
(48) .sup.1H NMR (500 MHz, CDCl.sub.3) δ: 7.50-7.44 (m, 1H), 7.25-7.17 (m, 3H), 7.15-7.13 (m, 1H), 7.11-6.96 (m, 12H), 6.91-6.85 (m, 2H), 6.74-6.63 (m, 2H), 6.52-6.46 (m, 2H), 3.59 (s, 3H), 3.38 (s, 3H).
(49) .sup.13C NMR (126 MHz, CDCl.sub.3) δ: 156.48, 155.81, 145.99, 145.86, 145.72, 145.60, 133.09, 132.98, 132.92, 132.83, 132.59, 132.43, 131.72, 131.68, 131.65, 131.25, 131.24, 131.08, 131.05, 130.98, 130.95, 130.87, 130.85, 128.46, 128.30, 127.25, 127.20, 127.17, 127.12, 126.94, 126.88, 126.78, 126.65, 126.58, 119.37, 109.89, 109.71, 54.65, 54.46.
(50) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: −3.40, −5.52.
(51) HR-MS m/z (%): Calcd for C.sub.32H.sub.28O.sub.2P [M.sup.++H] 475.1821; Found 475.1856(100).
Example 8. [2,6-bis(2-methoxyphenyl)phenyl]-dicyclohexylphosphine(HTPhos)
(52) ##STR00015##
(53) To an oven-dried 100 mL flask, equipped with a magnetic stir bar and a condenser, was charged with 2,6-bis(2-methoxylphenyl)-iodobenzene (0.83 g, 2.0 mmol) and TH (5.0 mL). Cooled to −78° C., 3.4 mL t-butyllithium (1.3 M solution in hexanes, 4.4 mmol) was added dropwise about 8 min, and the reaction solution was reacted for 2 h. Then Cy.sub.2PCl (0.47 g, 2.0 mmol) was added dropwise via cannula at −78° C. and the solution was warmed to room temperature for 6 h. The solvent was a removed in vacuum and 20 mL of brine was added, then the mixture was extracted with dichloromethane (3×20 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuum to give a light yellow oil. The residue was purified by column chromatography to give 0.76 g of [2,6-bis(2-methoxyphenyl)phenyl]-dicyclohexylphosphine as a white crystalline material, 78% yield. m.p.: 143.2-145.1° C.
(54) .sup.1H NMR (500 MHz, CDCl.sub.3) δ: 7.37-7.31 (m, 3H), 7.17-7.06 (m, 4H), 7.00-6.95 (m, 2H), 6.94-6.90 (m, 2H), 3.75 (s, 6H), 1.63-1.58 (m, 2H), 1.55-1.46 (m, 6H), 1.46-1.35 (m, 3H), 1.12-1.00 (m, 5H), 0.97-0.91 (m, 3H), 0.87-0.79 (m, 3H).
(55) .sup.31P NMR (202 MHz, CDCl.sub.3) δ: 5.75, 5.24.
(56) HR-MS m/z (%): Calcd for C.sub.32H.sub.40O.sub.2P [M.sup.++H] 487.2760; Found 487.2762(100).
Example 9. [2,6-bis(2-methoxyphenyl)phenyl]-di-tert-butylphosphine
(57) ##STR00016##
(58) To an oven-dried 100 mL flask, equipped with a magnetic stir bar and a condenser, was charged with 2,6-bis(2-methoxylphenyl)-iodobenzene (0.83 g, 2.0 mmol) and THE (5.0 mL). Cooled to −78° C., 3.4 mL t-butyllithium (1.3 M solution in hexanes, 4.4 mmol) was added dropwise about 15 min, and the reaction solution was reacted for 1 h. Then added the mixture of .sup.tBuPCl.sub.2(0.32 g, 2.0 mmol) and THE (3.0 mL) was added and stirred for 1 h, after that warmed to room tempeture for 6 h. Then t-BuLi (2.2 mL of a 1.0 M in pentane, 2.9 mmol) and mixture of CuCl (0.25 g, 2.5 mmol) and THE (10.0 mL) was added dropwise and the reaction solution was stirred for 1 h, then the reaction solution was heated to reflux for 24 h. Cooled to room tempeture, 40 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 0.27 g of [2,6-bis(2-methoxyphenyl)phenyl]-di-tert-butylphosphine as a white crystalline material), 31% yield.
(59) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: 23.69.
Example 10. [2,6-Bis(2,6-dimethoxyphenyl)phenyl]-diphenylphosphine
(60) ##STR00017##
Example 10-1
(61) To an oven-dried 100 mL flask, equipped with a magnetic stir bar and a condenser, and charged with magnesium (0.29 g, 12.0 mmol), ca. 1 mL of a solution of 2,6-dimethoxybromobenzene (2.39 g, 11.0 mmol) in THE (10.0 mL) was added and heated. After the reaction was initiated, the rest solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent. To another oven-dried two-neck 250 mL flask charged with TH (15 mL) and 3-chlorofluorobenzene (1.47 g, 5.0 mmol), n-butyllithium (2.4 mL of a 2.5 M solution in hexanes, 6.0 mmol) was added dropwise at −78° C. and stirred for 2 h. At that point the Grignard reagent was transferred via cannula to the solution, then warmed to room temperature, and the reaction solution was heated to 80° C. for 6 h. To a third oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with CuCl (0.6 g, 6.0 mmol), the above reaction solution was transferred via cannula and the mixture was a stirred for 20 min. Ph.sub.2PCl(1.32 g, 6.0 mmol) was added dropwise via cannula and the solution was heated to 70° C. for 3 h. 40 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 1.15 g of [2,6-bis(2,6-dimethoxyphenyl)phenyl]-diphenylphosphine as a orange crystalline material, 43% yield. m.p.: 154.2-156.2° C.
(62) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.52 (dd, J=10.6, 4.5 Hz, 1H), 7.16-6.85 (m, 14H), 6.29-6.13 (m, 4H), 3.53 (d, J=1.5 Hz, 12H).
(63) .sup.13C NMR (101 MHz, CDCl.sub.3) δ: 157.42, 141.41, 141.24, 137.46, 137.33, 135.37, 135.17, 133.96, 133.75, 131.34, 128.79, 128.57, 126.77, 126.70, 119.92, 119.86, 103.08, 55.12.
(64) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: −2.99.
(65) HR-MS m/z (%): Calcd for C.sub.34H.sub.32O.sub.4P [M.sup.++H] 535.2032; Found 535.2029 (100).
Example 10-2
(66) To an oven-dried 100 mL flask, equipped with a magnetic stir bar and a condenser, and charged with magnesium (0.67 g, 27.5 mmol), ca. 1 mL of a solution of 2,6-dimethoxybromobenzene (5.4 g, 25.0 mmol) in THE (15.0 mL) was added and heated. After the reaction was initiated, the rest solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent. To another oven-dried two-neck 250 mL flask with THE (15 mL) and 1,3-dichlorobenzene (1.47 g, 10.0 mmol), 5.0 mL n-butyllithium (2.5 M solution in hexanes, 12.0 mmol) was added dropwise at −78° C. and stirred for 1 h. At that point the Grignard reagent was transferred via cannula to the solution, then warmed to room temperature, and the reaction solution was heated to 70° C. for 6 h. Then added the mixture of Pd(PPh.sub.3).sub.4 (0.17 g, 0.15 mmol) and THE (5.0 mL) via cannula and the mixture was a stirred for 2 h. Ph.sub.2PCl (3.3 g, 15.0 mmol) was added dropwise via cannula and the solution was heated to 70° C. for 3 h. 40 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 2.56 g of [2,6-bis(2,6-dimethoxyphenyl)phenyl]-diphenylphosphine as a orange crystalline material), 48% yield.
Example 11. [2,6-Bis(2,6-dimethoxyphenyl)phenyl]-phenyl-isopropylphosphine
(67) ##STR00018##
(68) To an oven-dried 100 mL flask, equipped with a magnetic stir bar and a condenser, and charged with magnesium (0.56 g, 23.0 mmol), ca. 1 mL of a solution of 2,6-dimethoxyiodobenzene (5.81 g, 22.0 mmol) in THE (15.0 mL) was added and heated. After the reaction was initiated, the rest solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent. To another oven-dried two-neck 250 mL flask with THE (15 mL) and 1,3-dichlorobenzene (1.47 g, 10.0 mmol), 4.8 mL n-butyllithium (2.5 M solution in hexanes, 12.0 mmol) was added dropwise at −78° C. and stirred for 1 h. At that point the Grignard reagent was transferred via cannula to the solution, then warmed to room temperature, and the reaction solution was heated to 70° C. for 12 h. To a third oven-dried 100 mL flask, equipped with a magnetic stir bar and a condenser, with CuBr (1.72 g, 12.0 mmol), the above reaction solution was transferred via cannula and the mixture was a stirred for 20 min. PhPCl.sub.2 (2.15 g, 12.0 mmol) was added dropwise via cannula and the solution was heated to 70° C. for 12 h. 4.0 mL .sup.iPrMgBr (3.0 M solution in THF, 12.0 mmol) was added dropwise at −78° C. and the reaction solution was heated to 70° C. for 12 h. 40 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 2.90 g of [2,6-bis(2,6-dimethoxyphenyl)phenyl]-phenyl-isopropylphosphine as a white crystalline material, 58% yield. m.p.: 153.2-154.9° C.
(69) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.47 (t, J=7.5 Hz, 1H), 7.34 (ddd, J=18.9, 13.8, 6.7 Hz, 4H), 7.18 (d, J=7.4 Hz, 3H), 6.70 (d, J=8.3 Hz, 6H), 3.80 (s, 12H), 3.77 (s, 6H), 1.82 (s, 1H).
(70) .sup.13C NMR (101 MHz, CDCl.sub.3) δ: 157.90, 157.68, 141.00, 136.99, 134.01, 129.75, 129.31, 129.22, 128.44, 127.52, 124.60, ° C. 87, 120.04, 109.60, 104.45, 104.32, 56.15, 55.96, 16.88.
(71) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: −13.29.
Example 12. [2,6-Bis(2,4,6-triisopropylphenyl)phenyl]-diphenylphosphine
(72) ##STR00019##
(73) To an oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with magnesium (0.67 g, 27.5 mmol), ca. 1 mL of a solution of 2,4,6-triisopropylbromobenzene (7.08 g, 25.0 mmol) in THE (10.0 mL) was added and heated. After the reaction was initiated, the rest solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent. To another oven-dried two-neck 250 mL flask with THE (15 mL) and 1,3-dichlorobenzene (1.47 g, 10.0 mmol), n-butyllithium (5.0 mL of a 2.4 M solution in hexanes, 12.0 mmol) was added dropwise at −78° C. and stirred for 1 h. At that point the Grignard reagent was transferred via cannula to the solution, then warmed to room temperature, and the reaction solution was heated to 80° C. for 6 h. To a third oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with CuBr (2.15 g, 15.0 mmol), the above reaction solution was transferred via cannula and the mixture was a stirred for 15 min. Then Ph.sub.2PCl (3.31 g, 15.0 mmol) was added dropwise via cannula and the solution was heated to 70° C. for 6 h. Cooled to room temperature, 40 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 5.53 g of [2,6-bis(2,4,6-triisopropylphenyl)phenyl]-diphenylphosphine as a white crystalline material, 83% yield. m.p.: 148.4-149.6° C.
(74) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.42 (t, J=7.5 Hz, 1H), 7.20 (dd, J=7.5, 2.2 Hz, 2H), 7.00 (t, J=6.9 Hz, 2H), 6.96-6.83 (m, 8H), 6.78 (s, 4H), 2.89-2.77 (m, 6H), 1.26 (d, J=6.9 Hz, 12H), 0.91 (dd, J=34.9, 6.7 Hz, 24H).
(75) .sup.13C NMR (101 MHz, CDCl.sub.3) δ: 147.48, 147.26, 145.84, 138.05, 137.91, 137.27, 137.22, 134.65, 134.43, 132.29, 132.26, 127.64, 127.35, 127.31, 127.28, 120.51, 34.03, 30.91, 25.59, 24.03, 22.61.
(76) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: −5.89.
(77) HR-MS m/z (%): Calcd for C.sub.48H.sub.60P [M.sup.++H] 667.4427; Found 667.4479 (100).
Example 13. [2,6-Bis(2,4,6-triisopropylphenyl)phenyl]-phenyl-cyclohexylphosphine
(78) ##STR00020##
(79) To an oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with magnesium (0.67 g, 27.5 mmol), ca. 1 mL of a solution of 2,4,6-triisopropylbromobenzene (7.08 g, 25.0 mmol) in THE (10.0 mL) was added and heated. After the reaction was initiated, the rest solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent. To another oven-dried two-neck 250 mL flask with THE (15 mL) and 1,3-dichlorobenzene (1.47 g, 10.0 mmol), n-butyllithium (5.0 mL of a 2.4 M solution in hexanes, 12.0 mmol) was added dropwise at −78° C. and stirred for 1 h. At that point the Grignard reagent was transferred via cannula to the solution, then warmed to room temperature, and the reaction solution was heated to 80° C. for 6 h. To a third oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with CuBr (2.15 g, 15.0 mmol), the above reaction solution was transferred via cannula and the mixture was a stirred for 15 min. PhPCl.sub.2 (2.68 g, 15.0 mmol) was added dropwise via cannula at −78° C. and the solution was heated to 70° C. for 6 h, 15.0 mL CyMgBr (1.0 M solution in THF, 15.0 mmol) was added dropwise at −78° C. and the reaction solution was heated to 70° C. for 12 h. Cooled to room temperature, 40 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 4.91 g of [2,6-bis(2,4,6-triisopropylphenyl)phenyl]-phenyl-cyclohexylphosphine as a white crystalline material, 73% yield. m.p.: 146.5-148.1° C.
(80) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.36-7.30 (m, 1H), 7.15 (dd, J=7.6, 1.8 Hz, 3H), 7.06-6.96 (m, 6H), 6.88 (s, 2H), 2.97 (s, 4H), 2.69-2.60 (m, 2H), 1.34 (d, J=6.9 Hz, 17H), 1.29-1.20 (m, 1H), 1.02 (ddd, J=16.8, 13.2, 6.7 Hz, 27H), 0.89-0.78 (m, 2H).
(81) .sup.13C NMR (101 MHz, CDCl.sub.3) δ: 147.80, 146.67, 146.52, 146.20, 146.05, 146.05, 138.10, 138.05, 135.25, 135.03, 132.04, 132.02, 127.75, 127.13, 127.05, 126.53, 120.84, 120.45, 34.23, 33.01, 32.68, 32.04, 31.91, 31.02, 30.95, 30.93, 30.68, 30.61, 26.86, 26.81, 26.74, 26.68, 25.98, 25.85, 24.21, 24.15, 22.58, 22.44.
(82) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: 6.72.
(83) HR-MS m/z (%): Calcd for C.sub.48H.sub.66P [M.sup.++H] 673.4897; Found 673.4944 (100).
Example 14. [2,6-Bis(2,4,6-triisopropylphenyl)phenyl]-methyl-tert-butylphosphine (ZTPhos)
(84) ##STR00021##
(85) To an oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with magnesium (0.56 g, 23.0 mmol), ca. 1 mL of a solution of 2,4,6-triisopropylbromobenzene (6.23 g, 22.0 mmol) in THE (10.0 mL) was added and heated. After the reaction was initiated, the rest solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent. To another oven-dried two-neck 250 mL flask with THE (15 mL) and 1,3-dichlorobenzene (1.47 g, 10.0 mmol), n-butyllithium (4.8 mL of a 2.5 M solution in hexanes, 12.0 mmol) was added dropwise at −78° C. and stirred for 1 h. At that point the Grignard reagent was transferred via cannula to the solution, then warmed to room temperature, and the reaction solution was heated to 80° C. for 6 h. To a third oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with CuBr (1.72 g, 12.0 mmol), the above reaction solution was transferred via cannula and the mixture was a stirred for 15 min. The mixture of .sup.tBuPCl.sub.2 (1.90 g, 12.0 mmol) and THF (5 mL) was added dropwise via cannula at −78° C. and the solution was heated to 70° C. for 6 h, 12.0 mL MeMgBr (1.0 M solution in THF, 12.0 mmol) was added dropwise at −78° C. and the reaction solution was warmed to room temperature for 12 h. 40 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 3.09 g of [2,6-bis(2,4,6-triisopropylphenyl)phenyl]-methyl-tert-butylphosphine as a white crystalline material), 53% yield. m.p.: 145.3-146.7° C.
(86) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.33-7.27 (m, 1H), 7.16 (d, J=7.5 Hz, 2H), 7.05 (d, J=5.9 Hz, 4H), 2.98 (dp, J=13.5, 6.5 Hz, 2H), 2.80 (ddq, J=26.6, 13.1, 6.6 Hz, 4H), 1.45-1.25 (m, 24H), 1.04 (dd, J=10.1, 6.8 Hz, 12H), 0.96 (d, J=7.0 Hz, 3H), 0.76 (t, J=14.2 Hz, 9H);
(87) .sup.13C NMR (101 MHz, CDCl.sub.3) δ: 148.15, 147.96, 147.82, 146.22, 145.92, 139.18, 139.13, 137.37, 136.95, 131.90, 131.87, 126.54, 120.64, 120.09, 34.19, 31.02, 30.97, 30.95, 29.87, 29.68, 29.51, 29.35, 26.15, 25.83, 24.29, 24.05, 22.62, 8.33, 8.11;
(88) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: −3.33;
(89) HR-MS m/z (%): Calcd for C.sub.41H.sub.62P [M.sup.++H] 585.4853; Found 585.4857 (100).
Example 15. [2,6-Bis(2,4,6-triisopropylphenyl)phenyl]-phenyl-isopropylphosphine
(90) ##STR00022##
(91) To an oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, was charged with magnesium (0.56 g, 23.0 mmol), ca. 1 mL of a solution of 2,4,6-triisopropylbromobenzene (6.23 g, 22.0 mmol) in THE (10.0 mL) was added and heated. After the reaction was initiated, the rest solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent. To another oven-dried two-neck 250 mL flask with THE (15 mL) and 1,3-dichlorobenzene (1.47 g, 10.0 mmol), 4.8 mL n-butyllithium (2.5 M solution in hexanes, 12.0 mmol) was added dropwise at −78° C. and stirred for 1 h. At that point the Grignard reagent was transferred via cannula to the solution, then warmed to room temperature, and the reaction solution was heated to 70° C. for 12 h. To a third oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with CuBr (1.72 g, 12.0 mmol), the above reaction solution was transferred via cannula and the mixture was a stirred for 20 min. PhPCl.sub.2 (2.15 g, 12.0 mmol) was added dropwise via cannula and the solution was heated to 70° C. for 12 h, 4.0 mL .sup.iPrMgBr (3.0 M solution in THF, 12.0 mmol) was added dropwise at −78° C. and the reaction solution was heated to 70° C. for 12 h. 40 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 3.98 g of [2,6-bis(2,4,6-triisopropylphenyl)phenyl]-phenyl-isopropylphosphine as a white crystalline material), 63% yield. m.p.: 144.3-146.2° C.
(92) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.40-7.34 (m, 1H), 7.21 (d, J=7.0 Hz, 4H), 7.16-7.07 (m, 2H), 6.99 (t, J=9.5 Hz, 4H), 6.66 (s, 1H), 3.28-3.17 (m, 1H), 3.06 (s, 2H), 2.89 (s, 2H), 2.72-2.62 (m, 1H), 2.55 (s, 1H), 1.47-1.39 (m, 15H), 1.35 (d, J=6.9 Hz, 6H), 1.32 (d, J=6.8 Hz, 3H), 1.06 (d, J=6.6 Hz, 4H), 1.00-0.90 (m, 5H), 0.77 (d, J=6.7 Hz, 5H), 0.66 (dd, J=15.5, 6.7 Hz, 3H).
(93) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: −4.19.
(94) HR-MS m/z (%): Calcd for C.sub.45H.sub.62P [M.sup.++H] 633.4583; Found 633.4580 (100).
Example 16. [2,6-Bis(2,4,6-triisopropylphenyl)phenyl]-dicyclohexylphosphine (XTPhos)
(95) ##STR00023##
(96) To an oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with magnesium (0.56 g, 23.0 mmol), ca. 1 mL of a solution of 2,4,6-triisopropylbromobenzene (6.23 g, 22.0 mmol) in THE (10.0 mL) was added and heated. After the reaction was initiated, the rest solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent. To another oven-dried two-neck 250 mL flask was added THE (15 mL) and 1,3-dichlorobenzene (1.47 g, 10.0 mmol), n-butyllithium (4.8 mL of a 2.5 M solution in hexanes, 12.0 mmol) was added dropwise at −78° C. and stirred for 2 h. At that point the Grignard reagent was transferred via cannula to the solution, then warmed to room temperature, and the reaction solution was heated to 70° C. for 12 h. To a third oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with CuBr (1.72 g, 12.0 mmol), the above reaction solution was transferred via cannula and the mixture was a stirred for 15 min. Then a solution of Cy.sub.2PCl (2.79 g, 12.0 mmol) in THE (5.0 mL) was added dropwise via cannula and the solution was heated to 70° C. for 6 h. Cooled to room temperature, 40 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 4.13 g of [2,6-bis(2,4,6-triisopropylphenyl)phenyl]-dicyclohexylphosphine as a white crystalline material), 61% yield. m.p.: 147.5-149.1° C.
(97) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.30-7.25 (m, 1H), 7.14-7.12 (m, 1H), 7.11-7.10 (m, 1H), 7.07 (s, 4H), 3.01-2.92 (m, 2H), 2.84-2.72 (m, 4H), 1.83-1.71 (m, 3H), 1.63-1.53 (m, 5H), 1.48-1.40 (m, 5H), 1.36 (dd, J=11.7, 6.9 Hz, 24H), 1.22-1.15 (m, 2H), 1.11-1.04 (m, 2H), 1.00 (d, J=6.7 Hz, 13H), 0.89-0.81 (m, 4H).
(98) .sup.13C NMR (101 MHz, CDCl.sub.3) δ: 147.55, 147.38, 145.70, 139.30, 139.25, 131.82, 131.79, 126.53, 120.79, 34.16, 34.06, 33.79, 31.92, 31.75, 30.74, 30.62, 30.50, 27.35, 27.27, 27.17, 27.01, 26.38, 25.98, 24.16, 23.12.
(99) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: 9.62, 9.52.
(100) HR-MS m/z (%): Calcd for C.sub.48H.sub.72P [M.sup.++H] 679.5366; Found 679.5367 (100).
Example 17. [2,6-Bis(2,4,6-triisopropylphenyl)phenyl]-(2′,6′-dimethoxy-2-biphenylyl)-methylphosphine
(101) ##STR00024##
(102) To an oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, was charged with magnesium (0.56 g, 23.0 mmol), ca. 1 mL of a solution of 2,4,6-triisopropylbromobenzene (6.23 g, 22.0 mmol) in THE (10.0 mL) was added and heated. After the reaction was initiated, the rest solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent. To another oven-dried two-neck 250 mL flask with THE (15 mL) and 1,3-dichlorobenzene (1.47 g, 10.0 mmol), n-butyllithium (4.8 mL of a 2.5 M solution in hexanes, 12.0 mmol) was added dropwise at −78° C. and stirred for 2 h. At that point the Grignard reagent was transferred via cannula to the solution, then warmed to room temperature, and the reaction solution was heated to 70° C. for 12 h. Cooled to −78° C., PCl.sub.3(1.65 g, 12.0 mmol) was added, warmed to room temperature for 6 h. To a third oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with magnesium (0.39 g, 16.0 mmol), ca. 1 mL of a solution of 2′,6′-dimethoxy-2-bromobiphenylyl (4.39 g, 15.0 mmol) in THE (12.0 mL) was added and heated. After the reaction was initiated, the rest solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent. To a fourth oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with CuCl (1.49 g, 15.0 mmol), the above reaction solution was transferred via cannula and the mixture was a stirred for 15 min. at −78° C. and the solution was heated to 70° C. for 6 h. 12.0 mL MeMgBr (1.0 M solution in THF, 12.0 mmol) was added dropwise at −78° C. and the reaction solution was heated to 70° C. for 12 h. 60 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 2.89 g of [2,6-bis(2,4,6-triisopropylphenyl)phenyl]-(2′,6′-dimethoxy-2-biphenylyl)-methylphosphine as a white crystalline material, 39% yield.
(103) .sup.31P NMR (162 MHz, CDCl.sub.3) δ. 7.12.
Example 18. [2,6-Bis(2-methoxy-1-naphthalenyl)phenyl]-diphenylphosphine
(104) ##STR00025##
(105) To an oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with magnesium (0.67 g, 27.5 mmol), ca. 1 mL of a solution of 1-bromo-2-methoxynaphthalene (5.93 g, 25.0 mmol) in THE (10.0 mL) was added and heated. After the reaction was initiated, the rest solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent. To another oven-dried two-neck 250 mL flask with THE (15 mL) and 1,3-dichlorobenzene (1.47 g, 10.0 mmol), n-butyllithium (5.0 mL of a 2.4 M solution in hexanes, 12.0 mmol) was added dropwise at −78° C. and stirred for 2 h. At that point the Grignard reagent was transferred via cannula to the solution, then warmed to room temperature, and the reaction solution was heated to 70° C. for 12 h. Then added the mixture of Pd(PPh.sub.3).sub.4 (0.17 g, 0.15 mmol) and THE (5.0 mL) via cannula and the mixture was a stirred for 20 min at room temperature. Ph.sub.2PCl (3.3 g, 15.0 mmol) was added dropwise at −78° C. and the solution was heated to 70° C. for 6 h. 40 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 3.05 g of [2,6-bis(2-methoxy-1-naphthalenyl)phenyl]-diphenylphosphine as a white crystalline material, 53% yield. m.p.: 153.2-155.0° C.
(106) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.72-7.57 (m, 5H), 7.42 (dd, J=7.5, 5.7 Hz, 4H), 7.30 (ddd, J=7.4, 4.5, 2.5 Hz, 4H), 7.06-6.98 (m, 2H), 6.90-6.77 (m, 6H), 6.72 (t, J=7.4 Hz, 4H), 3.55 (d, J=4.4 Hz, 6H).
(107) .sup.13C NMR (101 MHz, CDCl.sub.3) δ: 154.07, 143.67, 143.51, 136.63, 136.39, 136.20, 136.07, 134.03, 133.71, 133.50, 132.14, 132.12, 129.27, 128.51, 127.73, 126.76, 126.44, 126.36, 126.06, 125.46, 124.77, 124.72, 122.98, 112.16, 55.26.
(108) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: −4.54.
(109) HR-MS m/z (%): Calcd for C.sub.40H.sub.32O.sub.2P [M.sup.++H] 575.2134; Found 575.2151 (100).
Example 19. [2,6-Bis(2-methoxy-1-naphthalenyl)phenyl]-dicyclohexylphosphine
(110) ##STR00026##
(111) To an oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, was charged with magnesium (0.56 g, 23.0 mmol), ca. 1 mL of a solution of 1-bromo-2-methoxynaphthalene (5.22 g, 22.0 mmol) in THF (10.0 mL) was added and heated. After the reaction was initiated, the rest solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent. To another oven-dried two-neck 250 mL flask with THE (15 mL) and 1,3-dichlorobenzene (1.47 g, 10.0 mmol), n-butyllithium (5.0 mL of a 2.4 M solution in hexanes, 12.0 mmol) was added dropwise at −78° C. and stirred for 2 h. At that point the Grignard reagent was transferred via cannula to the solution, then warmed to room temperature, and the reaction solution was heated to 70° C. for 12 h. To a third oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with CuBr (1.72 g, 12.0 mmol), the reaction mixture was transferred via cannula to the flask was stirred for 20 min. Then a solution of Cy.sub.2PCl (2.79 g, 12.0 mmol) in THE (5.0 mL) was added dropwise via cannula and the solution was heated to 70° C. for 6 h. Cooled to room temperature, 40 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was added with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 2.58 g of [2,6-bis(2-methoxy-1-naphthalenyl)phenyl]-dicyclohexylphosphine as a white crystalline material, 44% yield. m.p.: 156.3-157.6° C.
(112) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.94 (d, J=9.0 Hz, 2H), 7.86 (d, J=7.8 Hz, 2H), 7.43-7.33 (m, 8H), 7.27 (d, J=8.0 Hz, 3H), 3.98-3.90 (m, 6H), 1.48-1.19 (m, 11H), 0.95-0.41 (m, 11H).
(113) .sup.13C NMR (101 MHz, CDCl.sub.3) δ: 153.59, 144.78, 144.62, 139.65, 139.34, 134.59, 131.61, 131.57, 128.87, 128.69, 128.40, 127.80, 127.15, 127.10, 126.06, 125.81, 112.86, 57.01, 56.03, 33.11, 32.95, 32.93, 32.71, 31.55, 31.38, 29.74, 27.07, 27.01, 26.94, 26.91, 26.35.
(114) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: 9.76.
(115) HR-MS m/z (%): Calcd for C.sub.40H.sub.43P [M] 586.2995; Found 586.2965 (100).
Example 20. [2,6-Bis(2-methoxy-1-naphthalenyl)phenyl]-(4-dimethylamino-phenyl)-cyclohexylphosphine
(116) ##STR00027##
(117) To an oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with magnesium (0.67 g, 27.5 mmol), ca. 1 mL of a solution of 1-bromo-2-methoxynaphthalene (5.93 g, 25.0 mmol) in THE (10.0 mL) was added and heated. After the reaction was initiated, the rest solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent. To another oven-dried two-neck 250 mL flask with THE (15 mL) and 1,3-dichlorobenzene (1.47 g, 10.0 mmol), n-butyllithium (5.0 mL of a 2.4 M solution in hexanes, 12.0 mmol) was added dropwise at −78° C. and stirred for 2 h. At that point the Grignard reagent was transferred via cannula to the solution, then warmed to room temperature, and the reaction solution was heated to 70° C. for 12 h. To a third oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with CuCl (1.20 g, 12.0 mmol), the reaction mixture was transferred via cannula to the flask was stirred for 20 min. Cooled to −78° C., then a solution of CyPCl.sub.2 (2.22 g, 12.0 mmol) in THE (5.0 mL) was added dropwise via cannula and the solution was heated to 40° C. for 6 h. Cooled to −50° C., a solution of magnesium 4-dimethylaminophenyl bromide in THE (24.0 mmol) was added dropwise via cannula and the solution was heated to 70° C. for 6 days. 40 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 2.84 g of [2,6-bis(2-methoxy-1-naphthalenyl)phenyl]-(4-dimethylamino-phenyl)-cyclohexylphosphine as an orange crystalline material, 45% yield. m.p.: 157.2-158.9° C.
(118) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.93 (dd, J=8.9, 6.3 Hz, 3H), 7.77-7.69 (m, 1H), 7.57-7.51 (m, 3H), 7.44 (d, J=9.1 Hz, 2H), 7.29-7.24 (m, 2H), 7.20-7.13 (m, 2H), 7.10-7.05 (m, 1H), 7.02-6.98 (m, 1H), 6.28 (s, 2H), 5.98 (d, J=8.0 Hz, 2H), 4.01 (s, 3H), 3.76 (s, 3H), 2.80 (s, 6H), 2.11-2.00 (m, 1H), 1.82-1.54 (m, 4H), 1.48-1.17 (m, 4H), 1.11-0.86 (m, 3H).
(119) .sup.13C NMR (101 MHz, CDCl.sub.3) δ: 153.76, 153.74, 153.59, 149.15, 145.11, 144.86, 144.02, 143.93, 138.73, 138.42, 134.59, 134.42, 134.40, 134.28, 134.07, 132.03, 132.01, 131.36, 131.31, 129.10, 128.82, 128.72, 128.71, 128.47, 127.95, 126.99, 126.22, 126.16, 125.98, 125.50, ° C. 07, 122.81, 120.29, 120.18, 112.57, 112.49, 111.56, 111.49, 56.27, 55.34, 50.80, 40.37, 32.13, 32.06, 30.36, 30.19, 30.14, 26.94, 26.84, 26.71, 26.60.
(120) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: −9.15.
(121) HR-MS m/z (%): Calcd for C.sub.42H.sub.42NO.sub.2P [M] 623.2947; Found 623.2930 (100).
Example 21. [2,6-Bis(2-methoxy-1-naphthyl)phenyl]-bis(3,5-bis(trifluoromethyl) phenyl]phosphine
(122) ##STR00028##
(123) To an oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with magnesium (0.29 g, 12.0 mmol), ca. 1 mL of a solution of 1-bromo-2-methoxynaphthalene (2.61 g, 11.0 mmol) in THE (5.0 mL) was added and heated. After the reaction was initiated, the rest solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent. To another oven-dried two-neck 250 mL flask with THE (15 mL) and 1,3-dichlorobenzene (0.74 g, 5.0 mmol), n-butyllithium (2.4 mL of a 2.5 M solution in hexanes, 6.0 mmol) was added dropwise at −78° C. and stirred for 2 h. At that point the Grignard reagent was transferred via cannula to the solution, then warmed to room temperature, and the reaction solution was heated to 70° C. for 12 h. To a third oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with CuCl (0.6 g, 6.0 mmol), the reaction mixture was transferred via cannula to the flask was stirred for 20 min. Cooled to −78° C., then (3,5-ditrifluoromethylphenyl).sub.2PCl was added dropwise via cannula and the solution was warmed to room temperature and heated to reflux for 6 h. 50 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 2.03 g of [2,6-Bis(2-methoxy-1-naphthyl)phenyl]-bis[(3,5-bis(trifluoromethyl)phenyl]phosphine as a white crystalline material, 48% yield. m.p.: 151.1-152.6° C.
(124) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.77-7.69 (m, 5H), 7.55-7.49 (m, 2H), 7.45-7.42 (m, 4H), 7.41 (d, J=2.7 Hz, 1H), 7.40-7.38 (m, 1H), 7.38-7.36 (m, 1H), 7.35 (d, J=1.2 Hz, 1H), 7.33 (d, J=6.9 Hz, 4H), 7.08 (d, J=9.1 Hz, 2H), 3.68 (s, 6H).
(125) .sup.13C NMR (101 MHz, CDCl.sub.3) δ: 154.29, 143.38, 143.22, 138.54, 138.35, 133.63, 133.01, 132.78, 132.57, 132.54, 130.76, 130.25, 128.36, 128.02, 127.00, 124.57, ° C. 78, 121.82, 121.75, 112.56, 55.60, 1.11.
(126) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: −3.12.
(127) HR-MS m/z (%): Calcd for C.sub.44H.sub.27F.sub.12O.sub.2P [M] 846.1552; Found 846.1552(100).
Example 22. [2,6-Bis(2-methoxy-6-dimethylaminophenyl)phenyl]-diphenylphosphine
(128) ##STR00029##
(129) To an oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with magnesium (0.56 g, 23.0 mmol), ca. 1 mL of a solution of 2-methoxy-6-dimethylaminoliodobenzene (6.10 g, 22.0 mmol) in THE (10.0 mL) was added and heated. After the reaction was initiated, the rest solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent. To another oven-dried two-neck 250 mL flask with THE (15 mL) and 1,3-dichlorobenzene (1.47 g, 10.0 mmol), n-butyllithium 4.8 mL of a 2.5 M solution in hexanes, 12.0 mmol) was added dropwise at −78° C. and stirred for 2 h. At that point the Grignard reagent was transferred via cannula to the solution, then warmed to room temperature, and the reaction solution was heated to 70° C. for 12 h. To a third oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with CuCl (0.6 g, 6.0 mmol), the reaction mixture was transferred via cannula to the flask was stirred for 15 min. Cooled to −78° C. Then Ph.sub.2PCl (2.65 g, 12.0 mmol) was added dropwise via cannula and the solution was warmed to room temperature and stirred for 6 h. 50 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 1.57 g of [2,6-Bis(2-methoxy-6-dimethylaminophenyl) phenyl]-diphenylphosphine as a white crystalline material, 28% yield.
(130) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.73-7.62 (m, 3H), 7.35-7.27 (m, 7H), 7.19-7.12 (m, 3H), 6.41-6.28 (m, 6H), 3.80 (s, 6H), 2.94 (s, 12H).
(131) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: −13.62, −13.66.
Example 23. [2,6-Bis(2,4,6-triisopropylphenyl)phenyl]-bis(2-thienyl)phosphine
(132) ##STR00030##
(133) To an oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with magnesium (0.56 g, 23.0 mmol), ca. 1 mL of a solution of 2,4,6-triisopropylbromobenzene (6.23 g, 22.0 mmol) in THE (10.0 mL) was added and heated. After the reaction was initiated, the rest solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent. To another oven-dried two-neck 250 mL flask with THE (15 mL) and 1,3-dichlorobenzene (1.47 g, 10.0 mmol), n-butyllithium (4.8 mL of a 2.5 M solution in hexanes, 12.0 mmol) was added dropwise at −78° C. and stirred for 2 h. At that point the Grignard reagent was transferred via cannula to the solution, then warmed to room temperature, and the reaction solution was heated to 70° C. for 12 h. Cooled to −78° C., PCl.sub.3 (1.65 g, 12.0 mmol) was added, warmed to room temperature for 6 h. To third 250 mL flask, equipped with a magnetic stir bar and a condenser, was charged with magnesium (0.90 g, 37.0 mmol), ca. 1 mL of a solution of 2-bromine thiophene (5.87 g, 36.0 mmol) in THE (15.0 mL) was added and heated. After the reaction was initiated, the rest solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent. To a fourth oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with CuCl (1.19 g, 12.0 mmol), the reaction mixture was transferred via cannula to the flask was stirred for 15 min. Cooled to −78° C. Then Grignard reagent of 2-bromine thiophene was added dropwise via cannula and the solution was heated to 70° C. for 12 h. 40 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 3.59 g of [2,6-bis(2,4,6-triisopropylphenyl)phenyl]-bis(2-thienyl)phosphine as a blue crystalline material, 53% yield. m.p.: 144.3-145.5° C.
(134) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.47-7.40 (m, 1H), 7.26-7.23 (m, 2H), 7.23-7.18 (m, 2H), 6.88 (s, 4H), 6.79-6.75 (m, 2H), 6.75-6.70 (m, 2H), 2.85 (s, 6H), 1.30 (d, J=6.9 Hz, 12H), 1.04-0.92 (m, 24H).
(135) .sup.13C NMR (101 MHz, CDCl.sub.3) δ: 147.80, 146.63, 146.45, 146.19, 146.18, 139.55, 139.29, 136.76, 136.70, 135.63, 135.40, 135.20, 134.96, 132.31, 132.28, 131.55, 131.52, 127.93, 126.69, 126.63, 120.64, 34.17, 31.13, 25.58, 24.09, 22.70.
(136) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: −33.31.
(137) HR-MS m/z (%): Calcd for C.sub.44H.sub.56S.sub.2P [M.sup.++H] 679.3555; Found 679.3560(100).
Example 24. [2,6-Bis(2,6-dimethoxyphenyl)phenyl]-dicyclohexylphosphine (STPhos)
(138) ##STR00031##
(139) To an oven-dried 100 mL flask, equipped with a magnetic stir bar and a condenser, and charged with magnesium (0.67 g, 27.5 mmol), ca. 1 mL of a solution of 2,6-dimethoxybromobenzene (5.40 g, 25.0 mmol) in THE (10.0 mL) was added and heated. After the reaction was initiated, the rest solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent. To another oven-dried two-neck 250 mL flask with THE (15 mL) and 1,3-dichlorobenzene (1.47 g, 10.0 mmol), n-butyllithium (4.8 mL of a 2.5 M solution in hexanes, 12.0 mmol) was added dropwise at −78° C. and stirred for 2 h. At that point the Grignard reagent was transferred via cannula to the solution, then warmed to room temperature, and the reaction solution was heated to 70° C. for 12 h. Cooled to −78° C. A mixture of CyPCl.sub.2 (2.68 g, 15.0 mmol) and THE (5.0 mL) was added dropwise via cannula and the solution was heated to 70° C. for 6 h. Then CyMgCl (15.0 mL of a 1.0 M in THF, 15.0 mmol) and mixture of CuCl (1.49 g, 15.0 mmol) and THE (10.0 mL) was added dropwise at −78° C. and the reaction solution was heated to 70° C. for 12 h. 40 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 0.87 g of [2,6-bis(2,6-dimethoxyphenyl)phenyl]-dicyclohexylphosphine as a white crystalline material, 16% yield.
(140) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.38 (t, J=7.5 Hz, 1H), 7.35-7.28 (m, 2H), 7.06 (dd, J=7.5, 1.1 Hz, 2H), 6.61 (dd, J=8.2, 4.2 Hz, 4H), 3.72 (s, 12H), 1.70-1.48 (m, 12H), 1.33 (d, J=11.8 Hz, 2H), 1.12-0.78 (m, 10H).
(141) .sup.13C NMR (101 MHz, CDCl.sub.3) δ: 157.74, 142.25, 142.09, 137.92, 137.62, 130.98, 130.95, 128.25, 127.72, 121.92, 121.86, 103.12, 55.38, 33.70, 33.54, 32.38, 32.17, 31.98, 31.80, 27.64, 27.52, 27.44, 27.33, 26.67.
(142) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: 11.34.
Example 25. [2,6-Bis(2,4,6-triisopropylphenyl)phenyl]-bis[3,5-bis(trifluoromethyl)-phenyl]phosphine
(143) ##STR00032##
(144) To an oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with magnesium (0.56 g, 23.0 mmol), ca. 1 mL of a solution of 2,4,6-triisopropylbromobenzene (6.23 g, 22.0 mmol) in THE (10.0 mL) was added and heated. After the reaction was initiated, the rest solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent. To another oven-dried two-neck 250 mL flask with THE (15 mL) and 1,3-dichlorobenzene (1.47 g, 10.0 mmol), n-butyllithium (4.8 mL of a 2.5 M solution in hexanes, 12.0 mmol) was added dropwise at −78° C. and stirred for 2 h. At that point the Grignard reagent was transferred via cannula to the solution, then warmed to room temperature, and the reaction solution was heated to 70° C. for 12 h. Cooled to −78° C., PCl.sub.3 (1.65 g, 12.0 mmol) was added, warmed to room temperature for 6 h. To an third 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with magnesium (0.39 g, 16.0 mmol), ca. 1 mL of a solution of 3,5-bistrifluoromethylbromobenzene (4.40 g, 15.0 mmol) in THE (10.0 mL) was added and heated. After the reaction was initiated, the rest solution was added dropwise and the reaction mixture was heated to reflux for 2 h to obtain a Grignard reagent. To a fourth oven-dried 250 mL flask, equipped with a magnetic stir bar and a condenser, and charged with CuCl (1.48 g, 15.0 mmol), the above reaction solution was transferred via cannula and the mixture was a stirred for 30 min. The rest solution was added dropwise via cannula at −78° C. and the solution was heated to 70° C. for 12 h. 40 mL of ammonia (26.0%-28.0%) was added and stirred for 30 min, then the mixture was extracted with dichloromethane (3×50 mL), and the combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a light yellow oil. The residue was purified by column chromatography to give 4.03 g of [2,6-bis(2,4,6-triisopropylphenyl)-phenyl-bis[3,5-bis(trifluoromethyl)-phenyl]phosphine a white crystalline material, 43% yield. m.p.: 139.7-141.2° C.
(145) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 8.03 (s, 2H), 7.80 (d, J=7.0 Hz, 4H), 7.48-7.37 (m, 1H), 7.22 (d, J=7.4 Hz, 2H), 7.10 (d, J=8.5 Hz, 4H), 3.05-2.92 (m, 2H), 2.82-2.72 (m, 1H), 2.67-2.55 (m, 3H), 1.40-1.34 (m, 12H), 1.20 (t, J=6.0 Hz, 11H), 1.16 (t, J=6.1 Hz, 11H), 1.10 (s, 1H), 1.08 (s, 1H).
(146) .sup.13C NMR (101 MHz, CDCl.sub.3) δ: 148.30, 146.47, 145.92, 142.38, 137.48, 137.31, 136.54, 133.37, 133.34, 133.19, 133.12, 129.78, 128.49, 127.84, 126.50, 124.46, 124.42, 124.38, 124.08, 121.36, 120.69, 120.43, 34.28, 34.19, 30.89, 30.40, 29.73, 24.65, 24.30, 24.11, 24.08, 24.05, 23.51.
(147) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: −4.15.
Example 26. Trans-dichloro{bis[2,6-bis(2-methoxyphenyl)phenyl-diphenylphosphine]palladium(II)}
(148) ##STR00033##
(149) In an inert atmosphere, a 50 mL Shlenk bottle was charged with [2,6-bis(2-methoxyphenyl)phenyl]-diphenylphosphine (240.0 mg, 0.5 mmol) and di(acetonitrile) palladium chloride (65.0 mg, 0.25 mmol), and 5 mL of dichloromethane and the mixture was a stirred for 6 h. The solvent was a removed in vacuum and The residue was purified by recrystallization in methanol to give trans-dichloro{bis[2,6-bis(2-methoxyphenyl)phenyl-diphenylphosphine]palladium(II)} as a yellow solid (0.23 g, 77%).
(150) .sup.1H NMR (500 MHz, DMSO) δ: 7.50-7.44 (m, 1H), 7.25-7.17 (m, 3H), 7.15-7.13 (m, 1H), 7.11-6.96 (m, 12H), 6.91-6.85 (m, 2H), 6.74-6.63 (m, 2H), 6.52-6.46 (m, 2H), 3.59 (s, 3H), 3.38 (s, 3H).
(151) .sup.31P NMR (162 MHz, DMSO) δ: 30.94.
Example 27. Bis[(2,6-diphenyl-4-methylphenyl)-diphenylphosphine]palladium(0)
(152) ##STR00034##
(153) In an inert atmosphere, a 50 mL Shlenk bottle was a charged with (2,6-diphenyl-4-methylphenyl)-diphenylphosphine (236 mg, 0.55 mmol) and Me.sub.2Pd(II)(TMEDA) (67 mg, 0.25 mmol), and 2 mL of dichloromethane and the mixture was a stirred for 6 h. The solvent was a removed in vacuum and the residue was purified by recrystallization in acetone to give bis[(2,6-diphenyl-4-methylphenyl)-diphenylphosphine]palladium(0) as black solid (0.21 g, 70%).
(154) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: 26.04.
Example 28. Chloro[(2,6-diphenyl-4-methylphenyl)-diphenylphosphine-(N,N-dimethylbenzylamine-2-)palladium(II)]
(155) ##STR00035##
(156) In an inert atmosphere, a 50 mL Shlenk bottle was a charged with (2,6-diphenyl-4-methylphenyl)-diphenylphosphine (214.0 mg, 0.5 mmol) and chloro (N,N-dimethylbenzylamine-2-)palladium(II)(II) dimer(138.0 mg, 0.25 mmol), and 5 mL of dichloromethane and the mixture was a stirred for 6 h. The solvent was a removed in vacuum and the residue was purified by a short column (dichloromethane) to afford chloro[(2,6-diphenyl-4-methylphenyl)-diphenylphosphine-(N,N-dimethylbenzylamine-2-)palladium(II)] as a yellow solid (0.31 g, 90%).
(157) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.50-7.33 (m, 5H), 7.12-7.02 (m, 3H), 7.02-6.94 (m, 3H), 6.94-6.90 (m, 3H), 6.89 (s, 2H), 6.88-6.86 (m, 1H), 6.85 (d, J=3.1 Hz, 3H), 6.74-6.67 (m, 2H), 6.17-6.10 (m, 1H), 5.55-5.49 (m, 1H), 3.99 (d, J=1.2 Hz, 2H), 2.91 (d, J=2.4 Hz, 6H), 2.30 (s, 3H).
(158) .sup.13C NMR (101 MHz, CDCl.sub.3) δ: 149.05, 148.20, 148.18, 146.75, 146.67, 142.78, 142.74, 138.48, 138.46, 137.52, 137.42, 137.14, 137.03, 132.81, 132.73, 131.34, 130.86, 129.44, 129.41, 127.25, 127.14, 126.19, 124.38, 124.32, 123.56, 122.08, 50.63, 50.61, 29.72, 20.89.
(159) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: 42.51.
(160) HR-MS m/z (%): Calcd for C.sub.40H.sub.37NPPd [M.sup.+-Cl] 668.1708; Found 668.1755(100).
Example 29. Chloro{(2,6-diphenyl-4-methylphenyl)diphenylphosphine-[2-(2-aminoethyl)phenyl]}palladium(II)
(161) ##STR00036##
(162) In an inert atmosphere, a 50 mL Shlenk bottle was a charged with (2,6-diphenyl-4-methylphenyl)diphenylphosphine (214.0 mg, 0.5 mmol) and chloro [2-(2-aminoethyl)phenyl] palladium(II) dimer (130.0 mg, 0.25 mmol), and 10 mL of dichloromethane and the mixture was a stirred for 6 h. The solvent was a removed in vacuum and the residue was purified by a short column (dichloromethane) to afford chloro{(2,6-diphenyl-4-methylphenyl)diphenylphosphine-[2-(2-aminoethyl)phenyl]}palladium(II) as a yellow solid (0.27 g, 80%).
(163) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 8.06-7.95 (m, 1H), 7.76-7.69 (m, 1H), 7.64-7.30 (m, 12H), 7.21-7.10 (m, 4H), 7.08-6.91 (m, 4H), 6.65-6.58 (m, 2H), 6.56-6.50 (m, 1H), 6.49-6.42 (m, 2H), 2.46-2.40 (m, 3H), 1.58-1.52 (m, 4H), 1.47-1.44 (m, 2H).
(164) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: 22.69.
Example 30. Methanesulfonato{[2,6-bis(2,4,6-triisopropylphenyl)phenyl-dicyclohexylphosphine](2′-amino-1,1′-biphenyl-2-yl)palladium(II)}
(165) ##STR00037##
(166) In an inert atmosphere, a 50 mL Shlenk bottle was a charged with 2,6-bis(2,4,6-triisopropylphenyl)phenyl-dicyclohexylphosphine (271.0 mg, 0.4 mmol) and methanesulfonato-2′-amino-1,1′-biphenyl-2-yl)palladium(II) dimer (148.0 mg, 0.2 mmol), and 5 mL of dichloromethane and the mixture was a stirred for 6 h. The solvent was a removed in vacuum and the residue was purified by a short column (dichloromethane) to afford methanesulfonato{[2,6-bis(2,4,6-triisopropylphenyl)phenyl-dicyclohexylphosphine](2′-amino-1,1′-biphenyl-2-yl)palladium(II)} as yellow solid (0.37 g, 89%). .sup.31P NMR (162 MHz, CDCl.sub.3) δ: 59.07, 25.02.
Example 31. [(TXPhos)(allyl)PdCl]
(167) ##STR00038##
(168) In an inert atmosphere, a 50 mL Shlenk bottle was a charged with 2,6-bis(2,4,6-triisopropylphenyl)phenyl-dicyclohexylphosphine (135.0 mg, 0.2 mmol) and allyl palladium(II) chloride dimer (36.0 mg, 0.1 mmol), and 3 mL of dichloromethane and the mixture was a stirred for 6 h. The solvent was a removed in vacuum and the residue was purified by a short column (dichloromethane) to afford a yellow solid (0.15 g, 90%).
(169) .sup.31P NMR (162 MHz, CDCl.sub.3) δ: 67.00.
Example 32-38
(170) TABLE-US-00001 TABLE 1 The aminations of 4-Chloroanisole with Diphenylamine; XTPhos(example-16) as the ligand.sup.[a] Tem. Pd Source Time yield Example Base (° C.) Solvent (mol %) P:Pd (h) (%) 32 NaO.sup.tBu 100 toluene [PdCl(π-allyl)].sub.2 1:1 6 99 (0.25) 33 NaO.sup.tBu 100 toluene [PdCl(π-allyl)].sub.2 2:1 6 98 (0.25) 34 NaO.sup.tBu 100 toluene [PdCl(π-allyl)].sub.2 3:1 6 98 (0.25) 35 NaO.sup.tBu 100 toluene [PdCl(π-allyl)].sub.2 1:1 12 50 (0.05) 36 NaO.sup.tBu 100 toluene [PdCl(π-allyl)].sub.2 2:1 12 90 (0.05) 37 NaO.sup.tBu 100 toluene [PdCl(π-allyl)].sub.2 3:1 12 73 (0.05) 38.sup.[b] CH.sub.3MgCl 145 xylene [PdCl(π-allyl)].sub.2 2:1 1 86 (0.05) XTPhos:
Example 39,40
(171) TABLE-US-00002 TABLE 2 The aminations of 4-Chlorotoluene with Diphenylamine; ZTPhos(example-14) as the ligand .sup.[a] Example Pd Source (mol %) P:Pd Time (h) Yield (%) 39 [PdCl(π-allyl)].sub.2 2:1 6 90 (0.5) 40 Pd(OAc)].sub.2 2:1 6 66 (1.0) ZTPhos:
Example 41
(172) TABLE-US-00003 TABLE 3 The effect of ligand in the Suzuki reaction of 2- Bromotoluene with PhB(OH).sub.2.sup.[a] Catalyst Yield Example ligand (mol %) (%) 41 XTPhos 0.1 99 literature data.sup.[b] DmpPMe.sub.2.sup.[c] 1.0 91 .sup.[a]In glove box, a mixture of aryl halide (1.0 mmol), PhB(OH).sub.2 (1.5 mmol), dodecane (130 uL, 0.57 mmol), CsF (3.0 mmol), moderate of the ligand, Pd Source (P:Pd = 1:1) and 2 mL of dioxane was taken in pressure tubing and heated at 100° C. The organic phase was analyzed by GC. .sup.[b]R.C. Smith, et al., Tetrahedron Letters 2004, 45, 8327-8330. .sup.[c]DmpPMe.sub.2:
Example 42,43
(173) TABLE-US-00004 TABLE 4 The effect of ligand and it's complex in the aminations of 4-Chlorotoluene with carbazole.sup.[a] Tem Pd Source Time Yield Example Base (° C.) Solvent (mol %) P:Pd Ligand (h) (%) 42 NaO.sup.tBu 100 toluene [PdCl(π-allyl)].sub.2 2:1 XTPhos 3 92 (0.5) 43 NaO.sup.tBu 100 toluene [(XTPhos)(all)PdCl] — — 6 98 (0.5) literature NaO.sup.tBu 120 xylene [PdCl(π-allyl)].sub.2 2:1 cBRIDP.sup.[c] 3 95 data.sup.[b] (0.5) .sup.[a]In glove box, a mixture of aryl halide (1.1 mmol), carbazole (1.0 mmol), dodecane (130 uL, 0.57 mmol), NaOtBu (115 mg, 1.2 mmol), moderate of the ligand, Pd Source and 2 mL of toluene was taken in pressure tubing and heated at 100° C. The organic phase was analysed by GC. .sup.[b]Ken Suzuki, et al., Adv. Synth. Catal. 2008, 350, 652-656. .sup.[c]cBRIDP:
Example 44
(174) TABLE-US-00005 TABLE 5 The effect of ligand in the aminations of 4-Chlorotoluene with morpholine.sup.[a] Pd Ex- Tem. Sol- Source Time Yield ample Base (° C.) vent (mol %) P:Pd Ligand (h) (%) 44 NaO.sup.t 100° tol- Pd(OAc).sub.2 2:1 ZTPhos 1 97 Bu C. uene (1.0) lit- NaO.sup.t reflux tol- Pd(OAc).sub.2 2:1 8b-S.sup.[c] 12 83 erature Bu uene (2.5) data.sup.[b] ZTPhos:
Example 45
(175) TABLE-US-00006 TABLE 6 The effect of ligand in the Suzuki reaction of 1,3-dimethoxy-4,6- dibromobenzene with PhB(OH).sub.2, HTPhos(example-8) as the ligand.sup.[a] Pd Source Example (mol %) ligand P:Pd Time (h) yield (%) 45 Pd(OAc).sub.2 HTPhos 2:1 12 76 (1.0) literature Pd(OAc).sub.2 SPhos.sup.[c] 2:1 12 69 data.sup.[b] (1.0 HTPhos: