Synthesis of Diphosphine Ligands with an -Xylene Backbone

Borane {di(1-adamantyl)phosphine} complex (71)

To a stirred solution of di(1-adamantyl)phosphine (15) (13.5 g, 44.6 mmol) in THF (500 mL) BH3∙THF (99 mL, 99.7 mmol) was added. The almost colorless solution was stirred for further 12 hours. The volatiles were then removed in vacuum to quantitatively yield the product as a white solid (14.1 g, 44.6 mmol). ³¹P{¹H} NMR (162 MHz, CD2Cl2, 300 K): δ 40.9 (q br., ¹J(P,B) = 61.4 Hz).

Borane {1,2-bis[(di-1-adamantylphosphino)methyl]benzene} complex (73)^[28c,72c]

Sec-BuLi (37.5 mL, 52.5 mmol) was added to a cooled (-78 °C) suspension of the borane di(1-adamantyl)phosphine complex 71 (14.1 g, 44.6 mmol) in THF (400 mL). After 30 minutes stirring at -78 °C the suspension was allowed to warm to room temperature and stirred for further 120 minutes. The suspension was then again cooled to -78 °C and a solution of α,α’-dichloroxylene 72 (3.9 g, 22.3 mmol) in THF (50 mL) was added via cannula. The suspension was stirred for further 30 minutes at -78 °C. After warming to room temperature the mixture was stirred for another 12 hours and the solvent was removed under reduced pressure to yield the borane protected product 73 (16.5 g, 22.3 mmol). ¹H NMR (600 MHz, CD2Cl2, 300 K): δ 7.65 (m, 2H, Ar-H), 7.13 (m, 2H, Ar-H), 3.29 (d, ²J(P,H) = 11.9 Hz, 4H, CH2-H), 2.14-1.71 (m, 60H, Ad-H). ³¹P{¹H} NMR (162 MHz, CD2Cl2, 300 K): δ 40.8 (s br., P).

1,2-Bis[(di-1-adamantylphosphino)methyl]benzene (dadpx) (74)^[28c,72c]

To a cooled (0 °C) suspension of the borane complex 73 (16.5 g, 22.3 mmol) in methylene chloride (350 mL) HBF4·OEt2 (30.3 mL, 223.0 mmol) was added via syringe. The obtained mixture was

stirred for further 60 minutes at 0 °C and then allowed to warm to room temperature and stirred for another 12 hours. The mixture was then added to a cooled (0 °C), saturated, degassed NaHCO3

solution (500 mL) and stirred vigorously for 60 minutes. The formed precipitate was removed via filtration and washed with methylene chloride (2 x 200 mL). The resulting solution was extracted with methylene chloride (4 x 200 mL). The combined organic phases were dried over MgSO4 and filtrated. The colorless solution was evaporated to dryness, resulting in a white solid, which was recrystallized from an EtOH / CH2Cl2 mixture to yield 74 (dadpx) as white crystals (8.24 g, 11.7 mmol, 52.3 %). ¹H NMR (400 MHz, CDCl3,300 K): δ 7.55 (m, 2H, 3-H), 7.40 (m, 2H, 4-H), 3.00

To a cooled (0 °C), stirred suspension of 1-bromoadamantane (84) (21.5 g, 100 mmol) in H2SO4

(150 mL) phosphorus trichloride (46 mL, 500 mmol) was added dropwise. As soon as the reaction was completed the icebath was removed and the reaction mixture was stirred for further 24 hours at room temperature. The colorless solution was hydrolyzed with water (530 mL). After phase separation the organic layer was dried over MgSO4 and filtrated. The colorless solution was evaporated to dryness, resulting in a white solid, which was recrystallized from an acetone to give 85 as colorless crystals (12 g, 47.4 mmol, 47 %). ¹H NMR (400 MHz, C6D6, 300 K): δ 1.82 (q,

3J(P,H) = 7.9 Hz, ³J(H,H) = 2.9 Hz, 6H, 2-H), 1.64 (m, 3H, 3-H), 1.36-1.26 (m, 6H, 4-H). ¹³C{¹H}

NMR (400 MHz, C6D6, 300 K): δ 58.9 (d, ¹J(P,C) = 88.6 Hz, C1), 35.8 (s, C2), 35.1 (s, C4), 24.7 (d, ⁴J(P,C) = 15.2 Hz, C3). ³¹P{¹H} NMR (162 MHz, C6D6, 300 K): δ 61.9 (s, P).

1-Adamantyl-tert-butyl-phosphine oxide (88)^[76]

To a cooled (-10 °C) solution of 1-adamantyl-phosphinyl-dichloride (85) (8.0 g, 32 mmol) in toluene (150 mL) 44.4 mL of tert-BuLi solution (1.7 M in pentane) were added dropwise during 1 hour. After warming to room temperature the mixture was stirred for another 12 hours. To this mixture water (130 mL) was added and after phase separation the organic layer was dried over MgSO4 and filtrated. The solvent was removed under reduced pressure yielding compound 88 as a colorless solid, which was recrystallized from hexane (7.9 g, 29 mmol, 90 %). ¹H NMR (400 MHz, CDCl3, 300 K): δ 5.86 (d, ¹J(P,H) = 426.4 Hz, 1H, P-H), 2.04-1.98 (m, 9H, 3-H, 4-H), 1.77 (s, 6H, 2-H) 1.26 (d, ³J(P,H) = 14.9 Hz, 9H, 6-H). ¹³C{¹H} NMR (400 MHz, CDCl3, 300 K): δ 37.6 (d,

1J(P,C) = 60.7 Hz, C1), 36.7 (s, C2 and C4), 34.1 (d, ¹J(P,C) = 58.7 Hz, C5), 27.6 (d, ⁴J(P,C) = 9.9 Hz, C3), 25.9 (d, ²J(P,C) = 1.4 Hz, C6). ³¹P{¹H} NMR (162 MHz, CDCl3, 300 K): δ 63.2 (s, P).

MS (MALDI): m/z = 241.3 (M⁺ + H⁺).

Borane {(1-adamantyl-tert-butyl)phosphine} complex (87)^[79]

To a solution of 1-adamantyl-tert-butyl-phosphinoyl-oxide (88) (3.0 g, 11 mmol) in THF (150mL) water (2 g, 111 mmol, 10 equiv.) was added and after homogenization of the reaction mixture the temperature was cooled to 0 °C. BH3∙SMe2 complex (4.2 g, 11 mL of 5 M solution in diethyl ether, 55 mmol, 5 equiv.) was added dropwise via syringe. The reaction mixture was stirred at room temperature for further 2 hours and then evaporated to dryness. The crude product was washed with THF (3 x 100 mL). The white solid was removed via filtration and the filtrate was evaporated to dryness yielding 87 as a white solid containing the boronated phosphine (2.5 g, 10.5 mmol,

95.4 %). ¹H NMR (400 MHz, C6D6, 300 K): δ 3.62 (dq, ¹J(P,H) = 348.4 Hz, ²J(B,H) = 6.7 Hz ,1H,

n-BuLi (8.7 mL of a 2.5 M solution in hexanes, 14.0 mmol) was added to a cooled (0 °C) solution of borane (1-adamantyl-tert-butyl)phosphine (87) (3.3 g, 14 mmol) in THF (150 mL). After 30 minutes stirring at 0 °C the mixture was allowed to warm to room temperature and stirred for further 30 minutes. The pale yellow solution was again cooled to 0 °C and a solution of α, α’-dichloroxylene (72) (7.0 mmol, 1.2 g) in THF (50 mL) was added via cannula. The suspension was stirred for further 30 minutes at 0 °C. After warming to room temperature the mixture was stirred for another 12 hours and water (200 mL) was carefully added. The biphasic mixture was stirred for 1 hour and after phase separation the aqueous layer was washed with diethyl ether (3 x 100 mL). The combined organic layers were dried over MgSO4, filtered and evaporated to dryness yielding the crude product mix-89 as colorless solid (2.52 g, 4.4 mmol, 63 %). ¹H NMR (400 MHz, CDCl3, 300 K): δ 7.61 (dd, J = 5.4 and 3.5 Hz, 2H, H), 7.14 (dd, J = 5.7 and 3.6 Hz, 2H, Ar-H), 3.42 (dd, ²J(P,H) each = 15.0 and 11.8 Hz, 2H, benzyl-H), 3.26 (dd, ²J(P,H) each = 14.9 and 11.9 Hz, 2H, benzyl-H), 2.10 (m, 6H, Ad(CH)-H), 1.99 (m, 12H, Ad(CH2)-H), 1.71 (s, 12H,

Ad(CH2)-H), 1.27 (d, ³J(P,H) = 12.2 Hz, 18H, tBu-H). ³¹P{¹H} NMR (162 MHz, CD2Cl2, 300 K):

δ 40.8 (s br., P).

Separation of the diastereomeric mixture succeeded via several washing steps with methylene chloride (meso: 0.578 g, 1.0 mmol, 23 %; rac: 1.6 g, 2.8 mmol, 64 %).

1,2-Bis[(1-adamantyl-tert-butylphosphino)methyl]benzene (datbux) (rac-90 and meso-90)

Rac-1,2-bis[(1-adamantyl-tert-butylphosphino)methyl]benzene (rac-90). To a cooled (0 °C) suspension of rac-89 (1.6 g, 2.8 mmol) in methylene chloride (150 mL) HBF4·OEt2 (3.8 mL, 28 mmol) was added via syringe. The obtained mixture was stirred for further 60 minutes at 0 °C, allowed to warm to ambient temperature and stirred for a further 12 hours. The mixture was then added to a cooled (0 °C), saturated, degassed NaHCO3 solution (300 mL) and stirred vigorously for 60 minutes. The precipitate (mainly undissolved NaHCO3 and product) was removed via filtration and washed with methylene chloride (2 x 50 mL). The resulting solution was extracted with methylene chloride (3 x 100 mL). After phase separation, the combined organic phases were dried over MgSO4, filtrated and evaporated to dryness, resulting in an off-white solid, which was recrystallized from methanol to give diphosphine rac-90 (0.881 g, 1.6 mmol, 57 %) as white

MS (MALDI): m/z = 551.1 (M⁺ + H⁺), 493.1 (M⁺ - C4H9), 436.1 (M⁺ - 2 x C4H9). Anal Calc. (%) for C36H56P2: C: 78.50, H: 10.25. Found: C: 78.62, H: 10.32.

Meso-1,2-bis[(1-adamantyl-tert-butylphosphino)methyl]benzene (meso-90). To a cooled (0 °C) suspension of meso-89 (0.58 g, 1 mmol) in methylene chloride (100 mL) HBF4·OEt2 (1.4 mL, 10 mmol) was added via syringe. The obtained mixture was stirred for further 60 min. at 0 °C, allowed to warm to ambient temperature and stirred for a further 12 hours. The mixture was then added to a cooled (0 °C), saturated, degassed NaHCO3 solution (200 mL) and stirred vigorously for 60 minutes. The precipitate (mainly undissolved NaHCO3 and product) was removed via filtration and washed with methylene chloride (2 x 50 mL). The resulting solution was extracted with methylene chloride (3 x 100 mL). After phase separation, the combined organic phases were dried over

Bis[(1-di-1-adamantyl-2-di-tert-butylphosphino)methyl]benzene (100)

The precursor o-xylenediyl sulfate (98) was prepared according to literature.^[83] A 2.5 M solution of n-BuLi (4 mL, 10 mmol) in hexanes was added to a solution of the borane adduct of di(1-adamantyl)phosphine (71) (3.2 g, 10 mmol) in THF (30 mL) at room temperature and stirred for 30 min. Then a solution of the o-xylenediyl sulfate (98) (2 g, 10 mmol) in THF (30 mL) was added dropwise via syringe over 10 minutes. The mixture was stirred for 1 hour at this temperature and treated with a solution of in-situ generated LiPtBu2·BH3 (95)) (prepared from HPtBu2·BH3 (1.6 g, 10 mmol) and n-BuLi (4 mL, 10 mmol) in THF at room temperature). After 2 hours reaction time, the mixture was evaporated to dryness and the foamy residue was redissolved in methylene chloride. The solution was extracted with water and brine. After phase separation, the organic phase was dried over MgSO4, filtered and the solvent was removed under reduced pressure yielding an off-white solid of 96 (3.7 g, 6.4 mmol, 65 %).

The borane protected diphosphine 96 was treated with HBF4·OEt2 (8.7 ml, 64 mmol) at 0°C and stirred for 2 hours at room temperature. Evaporation of the solvent affords a colorless oil, which was diluted with methylene chloride and saturated NaHCO3 solution. After 1 hour, the resulting biphasic mixture was separated. The organic phase was dried over MgSO4, filtered and evaporated in vacuo yielding a colourless foam, which was recrystallized from methanol delivering the free diphosphine ligand (100) (0.7 g, 0.4 mmol, 20 %) as off-white solid. ¹H NMR (400 MHz, C6D6,

1J(P,C) = 24.3 Hz, C9), 32.2 (d, ¹J(P,C) = 24.8 Hz, C13), 30.2 (d, ²J(P,C) = 13.4 Hz, C14), 29.2

Di-tert-butylchlorophosphine (105) (10 g, 55 mmol) was diluted in pentane (200 ml) and cooled to -80 °C. MeLi (39.4 mL, 1.6 M in diethyl ether) was slowly added over 2 hours. The obtained suspension was stirred over night at room temperature and reacted with an aqueous solution of NH4Cl (15 mL, 29 g in 500 mL water). The resultant biphasic solution was separated, the organic phase extracted with diethyl ether, dried over MgSO4 and filtrated. The organic solvents were distilled off at room temperature yielding 107 as a colorless liquid (8.0 g, 49 mmol, 91 %).

1H NMR (400 MHz, C6D6, 300 K): δ 1.05 (d, ³J (P,H) = 10.7 Hz, 18H), 0.84 (d, ²J(P,H) = 4.5 Hz, 3H). ³¹P{¹H} NMR (162 MHz, C6D6, 300 K): δ 11.4 (s, P).

Di(iso-propyl)(methyl)phosphine (108)^[86]

Di-iso-propylchlorophosphine (106) (10 g, 66 mmol) was diluted in pentane (200 mL) and cooled to -80 °C. MeLi (47 mL, 1.6 M in diethyl ether) was slowly added over 2 hours. The obtained suspension was stirred over night at room temperature and reacted with an aqueous solution of NH4Cl (20 mL, 29 g in 500 ml water). The resultant biphasic solution was separated, the organic phase extracted with diethyl ether, dried over MgSO4 and filtrated. The organic solvents were distilled off at room temperature yielding 108 as a colorless liquid (8.3 g, 63 mmol, 95 %).

1H NMR (400 MHz, C6D6, 300 K): δ 1.48 (m, 4H), 1.00 (dd, ³J(P,H) = 14.5, ³J(H,H) = 7.1 Hz, 12H), 0.91 (dd, ³J(P,H) = 10.4, ³J(H,H) = 7.0 Hz, 12H), 0.75 (d, ²J(P,H) = 3.2 Hz, 3H).

31P{¹H} NMR (162 MHz, C6D6, 300 K): δ -10.6 (s, P).

[(Di-tert-butylphosphino)methyl]lithium (109)^[86]

Di(tert-butyl)methylphosphine (107) (5 g, 31 mmol) was diluted in heptane (80 mL) and tert-BuLi (37.5 mL, 60 mmol, 1.6 M in pentane) was added. The obtained mixture was stirred at 110 °C for 12 hours, yielding 109 as an off-white solid, which was centrifuged, washed with diethyl ether (3 x 70 mL) and dried in vacuo (3.5 g, 21 mmol, 68 %). ³¹P{¹H} NMR (162 MHz, THF-d8, 300 K):

δ 46.3 (s, P).

[(Di-iso-propylphosphino)methyl]lithium (110)^[86]

Di(iso-propyl)methylphosphine (108) (5 g, 38 mmol) was diluted in heptane (80 mL) and tert-BuLi (76 mmol, 57.5 mL, 1.6 M in pentane) was added. The obtained mixture was stirred at 110 °C for 12 hours, yielding 110 as an off-white solid, which was centrifuged, washed with diethyl ether (3 x 70 mL) and dried in vacuo (3.5 g, 25 mmol, 67 %). ³¹P{¹H} NMR (162 MHz, THF-d8, 300 K): δ 21.4 (s, P).

General Synthesis of Si-Diphosphine Ligands 113-116

The corresponding lithium salts 109 and 110 were suspended in THF and cooled to -80 °C. After 1 hour, the suspension was reacted with 0.5 equiv. of Cl2SiR2 (111 and 112). The obtained mixture was stirred over night at room temperature. The solvent was removed under reduced pressure, the obtained residue was diluted in pentane and extracted with water (3 x 100 mL). The organic phase was evaporated to dryness yielding compounds 113-116 as crude products.

Bis[(di-tert-butylphosphino)methyl]dimethylsilane (113)

Ligand 113 (1.3 g, 3.4 mmol, 57 %) was obtained as colorless crystals after crystallization from pentane by following the general procedure starting from lithium salt 109 (1.0 g, 6 mmol), and Cl2SiMe2 (111) (0.4 g, 3 mmol) in THF (50 mL). ¹H NMR (400 MHz, C6D6, 300 K): δ 1.11 (d,

3J(P,H) = 10.7 Hz, 36H, 3-H), 0.63 (d, ²J(P,H) = 4.0 Hz, 4H, 1-H), 0.36 (s, 6H, 4-H). ¹³C{¹H} NMR

(400 MHz, C6D6, 300 K): δ 31.6 (d, ¹J(P,C) = 26.4 Hz, C2), 29.8 (d, ²J(P,C) = 14.6 Hz, C3), 6.5 (dd, ¹J(P,C) = 44.4 Hz, ³J(P,C) = 5.8 Hz, C1), 0.28 (t, ³J(P,C) = 4.5 Hz, C4). ³¹P{¹H} NMR (162 MHz, C6D6, 300 K): δ 20.2 (s, P). MS (FAB): m/z = 319.2 (M⁺ - C4H9), 266.7 (M⁺ - 2 ´ C4H9), 207.0 (M⁺ - 3 ´ C4H9). Anal Calc. (%) for C20H46P2Si: C: 63.78, H: 12.3. Found: C: 62.78, H:

12.41.

Bis[(di-iso-propylphosphino)methyl]dimethylsilane (114)

Ligand 114 (1.1 g, 3.4 mmol, 31 %) was obtained as a yellow oil by following the general procedure starting from lithium salt 110 (1.5 g, 11 mmol), and Cl2SiMe2 (111) (0.7 g, 5 mmol) in THF (50 mL). ¹H NMR (400 MHz, C6D6, 300 K): δ 1.57 (vhept, J = 7 Hz, 4H, 2-H, 2’-H), 1.00 (dd, each ³J(P,H) = 13.6 Hz, ³J(H,H) = 7 Hz, ³J(P,H) = 11.6 Hz, ³J(H,H) = 7 Hz 4H, 3-H, 3’-H, 4-H, 4’-H), 0.49 (d, ¹J(P,H) = 3.7 Hz, 4H, 1-H), 0.23 (s, 6H, 5-H). ¹³C{¹H} NMR (400 MHz, C6D6, 300 K): δ 25.1 (d, ¹J(P,C) = 16.9 Hz, C2, C2’), 19.9 and 19.1 (d, each ²J(P,C) = 15.6 Hz and ²J(P,C) = 11.5 Hz, C3, C3', C4, C4'), 6.8 (dd, ¹J(P,C) = 39.0 Hz, ³J(P,C) = 5.3 Hz, C1), 0.03 (t, ¹J(P,C) = 4.9 Hz, C5). ³¹P{¹H} NMR (162 MHz, C6D6, 300 K): δ -5.2 (s, P). ). MS (FAB): m/z = 276.8 (M⁺ - C4H9), 235.1 (M⁺ - 2 ´ C4H9). Anal Calc. (%) for C16H38P2Si: C: 59.96, H: 11.95. Found: C: 57.76, H: 10.75.

Bis[(di-tert-butylphosphino)methyl]silolane (115)

Ligand 115 (0.98 g, 2.4 mmol, 27 %) was obtained as a yellow oil by following the general procedure starting from lithium salt 109 (1.5 g, 9 mmol), and 1,1-dichlorosilolane (112) (0.7 g, 4.5

mmol) in THF (75 mL). ¹H NMR (400 MHz, C6D6, 300 K): δ 1.74 (vqi,J(P,H) = 4.0 Hz, 4H, 2-H), procedure starting from lithium salt 110 (1.5 g, 11 mmol), and 1,1-dichlorosilolane (112) (0.78 g, 5.0 mmol) in THF (75 mL). ¹H NMR (400 MHz, C6D6, 300 K): δ 1.77 - 1.68 (m, 4H, 2-H), 1.57

Equimolar amounts of ligands 29-34, 38, 74, rac-90, meso-90 and 100 and Pd(dba)2 were dissolved in THF (20 mL) and stirred for 12 hours at room temperature. The obtained red solution was filtered through a syringe filter and evaporated to dryness. The red residue was suspended in pentane. The obtained precipitate was repeatedly dispersed in pentane (3 x 20 mL), centrifuged, and separated