Synthesis of Diphosphine Ligands with an o-Tolyl-Backbone

o-Bromo-benzyl-di(tert-butyl)phosphine (20)

The known compound 20 was prepared corresponding to literature.^[47a,48] o-Bromo-benzylbromide 10 (6.3 g, 25 mmol) and di(tert-butyl)phosphine 14 (5.4 g, 26 mmol) were dissolved in acetonitrile

(100 mL) and stirred at room temperature for a period of 24 hours. The acetonitrile was then removed in vacuo. To the obtained white solid degassed water (30 mL), degassed triethylamine (5.7 mL), degassed toluene (40 mL), and degassed ethanol (30 mL) were added. Upon phase separation, the upper toluene layer was separated, dried over MgSO4 and evaporated to dryness, resulting in a pale yellow oil of compound 20 (10.1 g, 21.5 mmol, 86 %). ¹H NMR (400 MHz, C6D6, 300 K): δ = 7.76 (m, 1H, Ar-H), 7.39 (vdd, J = 8.0, 0.8 Hz, 1H, Ar-H), 6.96 (vtd, J = 7.7, 1.1 Hz, 1H, Ar-H), 6.65 (vtd, J = 8.0, 1.4 Hz, 1H, Ar-H), 2.94 (d, ²J(P,H) = 2.7 Hz, 2H, benzyl-H), 1.06 (d, ³J(P,H) = 10.8 Hz, 18H, tBu-H). ³¹P{¹H} NMR (162 MHz, C6D6, 300 K): δ 34.4 (s, P).

o-Lithium-benzyl-di(tert-butyl)phosphine (23)

Compound 23 was prepared according to a literature procedure.^[46,89] 20 (3.20 g, 10.2 mmol) was dissolved in pentane (50 mL) and n-BuLi in hexanes (6.34 mL, 1.6 M, 10.2 mmol) was added at room temperature, resulting in the immediate formation of a white precipitate. The mixture was stirred for two hours, and then filtered. After washing with pentane and drying in vacuo, compound 23 was obtained as a white solid (1.7 g, 7 mmol, 69 %) which was used without further purification.

Identification as o-deuterium-benzyl-di(tert-butyl)phosphine after quenching with methanol-d4:

1H NMR (400 MHz, C6D6, 300 K): δ 7.28 (d, J = 7.5 Hz, 1H, Ar-H), 7.12 (m, 2H, Ar-H), 7.00 (d, J = 7.2 Hz, 1H, Ar-H), 2.66 (d, ²J(P,H) = 3.2 Hz, 2H, benzyl-H), 0.98 (d, ³J(P,H) = 10.8 Hz, 18H, tBu-H). ³¹P{¹H} NMR (162 MHz, C6D6, 300 K): δ 23.5 ppm. MS (FAB): m/z = 179.0 (M⁺ - C4H9).

Anal Calc. (%) for C15H24LiP: C: 74.35, H: 10.0. Found: C: 73.7, H: 9.97.

o-Bromo-benzyl-di(1-adamantyl)phosphine (24)

Compound 24 was prepared by a similar route which was used to prepare 20. o-Bromo-benzylbromide 10 (7.9 g, 32 mmol) and di(1-adamantyl)phosphine 15 (10 g, 33 mmol) were suspended in acetonitrile (300 mL). Heating the white suspension yields a colorless solution, from which a white solid precipitates immediately. The mixture was stirred for 12 hours before the solvent was removed under reduced pressure. To the crude reaction mixture degassed water (60 mL), toluene (100 mL), triethylamine (7.25 mL), and ethanol (20 mL) were added. After separation of the layers the organic phase was dried over MgSO4. Removal of the solvent led to a white solid. After recrystallization from an EtOH / CH2Cl2 mixture, compound 24 was obtained as colorless crystals (9.9 g, 21 mmol, 65 %). ¹H NMR (400 MHz, C6D6, 300 K): δ 7.91 (vddd, J = 7.8, 3.2, 1.7 Hz, 1H; 5-H), 7.44 (dd, ³J(H,H) = 8.0 and ⁴J(H,H) = 0.9 Hz, 1H; 2-H), 7.02 (td, ³J(H,H)

= 7.7 and ⁴J(H,H) = 1.2 Hz, 1H; 4-H), 6.67 (td, ³J(H,H) and ⁴J(H,H) = 7.9, 1.6 Hz, 1H; 3-H), 3.01 (d, ²J(P,H) = 2.9 Hz, 2H; 7-H), 2.11 – 1.54 (m, 30H, 9-11-H). ¹³C{¹H} NMR (101 MHz, C6D6, 300 K): δ 142.3 (d, ²J(P,C) = 14.5 Hz, C6), 132.9 and 132.7 (s each, C2 and C5), 127.2 (s, C3), 127.0 (d, ⁴J(P,C) = 2.0 Hz, C4), 125.6 (d, ³J(P,C) = 3.6 Hz, C1), 41.0 (d, ²J(P,C) = 11.2 Hz, C9, C9’), 37.1 (d, ⁴J(P,C) = 0.9 Hz, C11, C11’), 36.9 (d, ¹J(P,C) = 24.7 Hz, C8, C8’), 28.9 (d, ³J(P,C)

= 8.0 Hz, C10, C10’), 24.2 (d, ¹J(P,C) = 23.4 Hz, C7).³¹P{¹H} NMR (162 MHz, C6D6, 300 K): δ 32.5 (s, P). MS (FAB): m/z = 391.3 (M⁺-Br). Anal Calc. (%) for C27H36BrP: C: 69.12, H: 7.71.

Found: C: 68.80, H: 7.71.

o-Bromo-benzyl-di(cyclohexyl)phosphine (22)

Compound 22 was prepared by a similar route that was used to prepare 20.^[47a,48] o-Bromo-benzylbromide 10 (3.0 g, 12.2 mmol) and di(cyclohexyl)phosphine 16 (2.5 g, 12.6 mmol) were dissolved in acetonitrile (30 mL) and stirred for 24 hours at ambient temperature, resulting in the immediate formation of colorless crystals, which were separated and dried in vacuo. To the crystals degassed water (30 mL), toluene (30 mL), triethylamine (2.8 mL), and ethanol (20 mL) were added.

After separation of the layers the organic phase was dried over MgSO4. Removal of the solvent led to a white solid. After recrystallization from ethanol, compound 22 was obtained as colorless crystals (2.0 g, 5.4 mmol, 45 %).¹H NMR (400 MHz, C6D6, 300 K): δ 7.46 and 7.41 (d each, J(H,H) = 7.7 and 8.0 Hz, 1:1H, 2- and 5-H), 6.94 and 6.64 (vt each, J(H,H) = 7.3 and 7.5 Hz 1:1H, 3- and 4-H), 2.94 (d, ²J(P,H) = 1.8 Hz, 2H, 7-H), 2.16 – 0.43 (m, 22H, 8-11-H). ¹³C{¹H} NMR (101 MHz, CDCl3, 300 K): δ 140.7 (d, ²J(P,C) = 9.6 Hz, C6), 133.1 (s, C2), 132.0 (d, ³J(P,C) = 12.0 Hz, C5), 127.3 (s, C3 and C4), 125.3 (d, ³J(P,C) = 3.9 Hz, C1), 34.1 (d, ¹J(P,C) = 17.1 Hz, C8 and C8’); 30.2, 29.9, 27.7, and 27.6 (d each, J(P,C) = 12.4, 11.1, 6.5, and 4.9 Hz, C9, C10, C12, C13, C9’, C10’, C12’, and C13’), 29.5 (d, ¹J(P,C) = 22.4 Hz, C7), 29.9 (s, C11 and C11’). ³¹P{¹H}

NMR (162 MHz, C6D6, 300 K): δ 2.8 (s, P). MS (FAB): m/z = 287.1 (M⁺-Br), 205.1 (M⁺ -Br-C6H11). Anal Calc. (%) for C19H28BrP: C: 62.13, H: 7.68. Found: C: 61.62, H: 7.28.

Di(1-adamantyl)bromophosphine (39)^[49]

Di(1-adamantyl)bromophosphine (39) was prepared by dissolving di(1-adamantyl)phosphine (15) (3.6 g, 11.9 mmol) and CBr4 (3.3 g, 11.0 mmol) in methylene chloride. After 5 minutes the solvent

was removed in vacuo yielding 39 as a white solid (4.2 g, 11.0 mmol, 95 %) which was used without further purification. NMR data is in accordance with reported data.^[49]1H NMR (400 MHz, CD2Cl2, 300 K): δ 1.95 – 1.59 (m, 30H). ³¹P{¹H} NMR (162 MHz, CD2Cl2, 300 K): δ 146.39 (s, P).

o-Di(tert-butyl)phosphino-benzyl-di(tert-butyl)phosphine (29)

o-Lithium-benzyl-di(tert-butyl)phosphine (23) (1.7 g, 6.9 mmol) was dissolved in THF (20 mL) and cooled to -80 °C. To this solution di(tert-butyl)chlorophosphine (26) (1.4 g, 7 mmol) was added, stirred for another hour at -80 °C, warmed to room temperature, and stirred for further 24 hours. Removal of the solvent gave a brown solid, which was recrystallized from ethanol to give light yellow crystals of compound 29 (1.9 g, 5 mmol, 78 %).¹H NMR (400 MHz, C6D6, 300 K): δ 8.25 (m, 1H, 5-H), 7.79 (d, ³J(H,H) = 7.7 Hz, 1H, 2-H), 7.28 (m, 1H, 4-H), 7.12 (m, 1H, 3-H), 3.68 (dd, ²J(P,H) and ⁴J(P,H) = 5.1 and 3.4 Hz, 2H, 7-H), 1.32 and 1.30 (d each, ³J(P,H) = 11.9 and 10.5 Hz, 36H, 11-H, 11’-H, 9-H and 9’-H). ¹³C{¹H} NMR (101 MHz, C6D6, 300 K): δ 149.5 (dd, ²J(P,C) each = 26.2 and 11.4 Hz, C6), 136.4 (dd, ¹J(P,C) = 24.4, ³J(P,C) = 4.6 Hz, C1), 135.5 (d, ²J(P,C)

= 2.7 Hz, C2), 131.5 (dd, ³J(P,C) each = 19.5 and 5.1 Hz, C5), 128.8 (s, C4), 124.3 (d, ³J(P,C) = 2.1 Hz, C3), 32.9 (d, ¹J(P,C) = 24.2 Hz, C10, C10’), 32.3 (d, ¹J(P,C) = 23.8 Hz, C8, C8’), 30.8 and 30.1 (d each, ²J(P,C) each = 13.5 and 15.0 Hz, C9 and C11), 28.2 (dd, ¹J(P,C) = 30.0 and ³J(P,C)

= 23.1 Hz, C7). ³¹P{¹H} NMR (162 MHz, C6D6, 300 K): δ 35.0 (d, ⁴J(P,P) = 5.8 Hz, P2), 15.0 (d,

4J(P,P) = 5.8 Hz, P1). MS (FAB): m/z = 323.2 (M+ - C4H9), 267.1 (M⁺ - 2 ´ C4H9), 210.3. Anal Calc. (%) for C23H42P2: C: 72.58, H: 11.15. Found: C: 72.5, H: 11.42.

o-Di(cyclohexyl)phosphino-benzyl-di(tert-butyl)phosphine (30)

o-Lithium-benzyl-di(tert-butyl)phosphine (23) (1.2 g, 5.0 mmol) was dissolved in THF (20 mL) and cooled to -80 °C. This solution was reacted by addition of di(cyclohexyl)chlorophosphine (28) (1.1 g, 5.5 mmol), stirred for another hour at -80 °C, warmed to room temperature and stirred for 24 hours. All volatiles were removed and the yellow solid was recrystallized from ethanol to give white crystals of 30 (2.0 g, 4.7 mmol, 94 %).¹H NMR (400 MHz, C6D6, 300 K): δ 8.10 (m, 1H, 5-H), 7.37 (d, ³J(H,H) = 7.6 Hz, 1H, 2-H), 7.20 (vt, J = 6.9 Hz, 1H, 4-H), 7.05 (vt, J = 7.3 Hz, 1H, 3-H), 3.57 (dd, ²J(P,H) = 5.2 and ⁴J(P,H) = 2.3 Hz, 2H, 7-H), 2.04 – 0.95 (m, 22H, 10-15-H and 10’-15’-H), 1.20 (d, ²J(H,H) = 10.6 Hz, 18H, 9-H and 9’-H). ¹³C{¹H} NMR (101 MHz, C6D6, 300 K): δ 149.2 (dd, ²J(P,C) each = 23.3 and 11.8 Hz, C6), 133.8 (dd, ¹J(P,C) = 17.9 and ³J(P,C) = 3.1 Hz, C1), 132.8 (d, ²J(P,C)= 2.8 Hz, C2), 131.5 (dd, ³J(P,C) each = 18.6 and 4.4 Hz, C5), 128.6 (s, C4), 125.0 (d, ³J(P,C) = 1.8 Hz, C3), 34.0 (d, ¹J(P,C) = 14.2 Hz, C10, C10’), 32.4 (d, ¹J(P,C) = 23.7 Hz, C8, C8’), 30.8; 29.2, 27.6, and 27.4 (d each, J(P,C) = 16.7, 8.0, 11.8, and 6.9 Hz, C11, C12, C14, C15, C11’, C12’, C14’, and C15’), 30.2 (dd, ²J(P,C) = 13.6 and ⁶J(P,C) = 1.3 Hz, C9 and C9’), 27.3 (dd, ¹J(P,C) = 27.3 and ³J(P,C) = 22.4 Hz, C7), 26.7 (s, C13 and C13’).

31P{¹H} NMR (162 MHz, C6D6, 300 K): δ 36.4 (s, P2), -17.6 (s, P1). MS (FAB): m/z = 375.4 (M+

- C4H9), 319.2 (M⁺ - 2 ´ C4H9). Anal Calc. (%) for C27H46P2: C: 74.94, H: 10.74. Found: C: 74.83, H: 10.26.

o-Di(iso-propyl)phosphino-benzyl-di(tert-butyl)phosphine (31)

tert-BuLi (0.6 g, 9.5 mmol) was added to a cooled solution (-80 °C) of brombenzyl-di(tert-butyl)phosphine (20) (1.5 g, 4.8 mmol) in THF (50 mL). After 20 minutes the in-situ generated o-lithium-benzyl-di(tert-butyl)phosphine (23) was reacted with di(iso-propyl)chlorophosphine (27) (0.8 g, 5.2 mmol) and stirred for one hour at -80 °C. After warming to room temperature the mixture was stirred for another 12 hours and the solvent was removed under reduced pressure. The obtained brown solid was dispersed in diethyl ether and filtered through a syringe filter. The pale yellow solution was evaporated to dryness. The residue was recrystallized from ethanol to give white

o-Di(tert-butyl)phosphino-benzyl-di(1-adamantyl)phosphine (32)

To a cooled solution (-80 °C) of o-bromo-benzyl-di(1-adamantyl)phosphine (21) (1.7 g, 3.6 mmol) in THF (25 mL) tert-BuLi (0.41 g, 7.0 mmol) was added. Complete conversion to the corresponding o-lithium-benzyl-di(1-adamantyl)phosphine (24) was confirmed by NMR spectroscopy. After 1 hour the in-situ generated o-lithium-benzyl-di(1-adamantyl)phosphine (24) was reacted with di(tert-butyl)chlorophosphine (26) (0.7 g, 3.9 mmol) and stirred for one hour at -80 °C. After warming to room temperature the yellow solution was stirred for another 12 hours and the solvent was removed under reduced pressure. The resulting yellow foam was dispersed in Et2O and filtered through a syringe filter. The yellow solution was evaporated to dryness, resulting in a white solid, which was recrystallized from an EtOH / CH2Cl2 mixture to give the diphosphine 32 as white needles (1.2 g, 2.3 mmol, 63 %). ¹H NMR (400 MHz, C6D6, 300 K): δ 8.27 (m, 1H,

o-Di(cyclohexyl)phosphino-benzyl-di(1-adamantyl)phosphine (33)

To a cooled solution (-80 °C) of o-bromo-benzyl-di(1-adamantyl)phosphine (21) (1.6 g, 3.3 mmol) in THF (20 mL) tert-BuLi (0.41 g, 6.6 mmol) was added. After 1 hour the in-situ generated o-lithium-benzyl-di(1-adamantyl)phosphine (24) was reacted with di(cyclohexyl)chlorophosphine (28) (0.9 g, 3.6 mmol) and stirred for one hour at -80 °C. After warming to room temperature the pale yellow suspension was stirred for another 12 hours and the solvent was removed under reduced pressure. The white residue was recrystallized from an EtOH / CH2Cl2 mixture to give diphosphine 33 as white crystals (1.1 g, 2.0 mmol, 62 %). ¹H NMR (400 MHz, CD2Cl2, 300 K): δ 7.72 (m, 1H, 5-H), 7.34 (d, ³J(H,H) = 7.5 Hz, 1H, 2-H), 7.23 (vt, J = 7.5 Hz, 1H, 4-H), 7.10 (vt, J = 7.4 Hz, 1H, 3-H), 3.22 (dd, ²J(P,H) = 6.0 and ⁴J(P,H) = 4.1 Hz, 2H, 7-H), 2.03 – 0.81 (m, 52H, 9-11-H, 9’-11’-H, 12-17-9’-11’-H, and 12’-17’-H). ¹³C{¹H} NMR (101 MHz, CD2Cl2, 300 K): δ 150.3 (dd, ²J(P,C) each

= 23.7 and 13.6 Hz, C6), 133.8 (dd, ¹J(P,C) = 17.4 and ³J(P,C) = 4.0 Hz, C1), 133.1 (d, ²J(P,C) = 2.8 Hz, C2), 131.5 (dd, ³J(P,C) each = 19.8 and 4.4 Hz, C5), 128.3 (s, C4), 124.7 (d, ³J(P,C) = 1.9 Hz, C3), 41.4 (d, ²J(P,C) = 10.6 Hz, C9, C9’), 37.0 (s, C11, C11’), 37.3 (d, ¹J(P,C) = 19 Hz, C8, C8’), 34.2 (d, ³J(P,C) = 13.6 Hz, C10, C10’), 30.5 (d, ¹J(P,C) = 17.0 Hz, C12, C12’), 28.7, 28.6, 27.4, 27.2, and 26.5 (d each, J = 8.0, 6.8, 12.3, 7.1, and 1.1 Hz, C13-C17 and C13’-C17’), 22.3 (dd, ¹J(P,C) = 28.1 and ³J(P,C) = 19.7 Hz, C7). ³¹P{¹H} NMR (162 MHz, CD2Cl2, 300 K): δ 38.1 (s, P2), -17.7 (s, P1). MS (FAB): m/z = 454.1 (M⁺ - C6H11). Anal Calc. (%) for C39H58P2: C: 79.55, H: 9.93. Found: C: 79.60, H: 9.97.

o-Di(cyclohexyl)phosphino-benzyl-di(cyclohexyl)phosphine (34)

To a cooled solution (-80 °C) of o-bromo-benzyl-di(cyclohexyl)phosphine (22) (1.5 g, 4.1 mmol) in THF (20 mL) tert-BuLi (0.3 g, 8.2 mmol) was added. After 15 minutes the in-situ generated o-lithium-benzyl-di(cyclohexyl)phosphine (25) was reacted with di(cyclohexyl)chlorophosphine (28) (1.0 g, 4.5 mmol) and stirred for one hour at -80 °C. After warming to room temperature the pale yellow solution was stirred for another 12 hours and the solvent was removed under reduced pressure. The white foam was dispersed in diethyl ether, filtered through a syringe filter and evaporated to dryness. After recrystallization from ethanol the diphosphine 34 was obtained as white crystals (1.7 g, 3.5 mmol, 87 %). ¹H NMR (400 MHz, C6D6, 300 K): δ 7.76 (m, 1H, 5-H),

o-Di(1-adamantylphosphino)-benzyl-di(1-adamantyl)phosphine (38)

To a cooled solution (-80 °C) of o-bromo-benzyl-di(1-adamantyl)phosphine (21) (2.2 g, 4.6 mmol) in THF (20 mL) tert-BuLi (0.54 g, 9.3 mmol) was added. After 1 hour the in-situ generated o-lithium-benzyl-di(1-adamantyl)phosphine (24) was reacted with di(1-adamantyl)bromophos-phine (39) (1.95 g, 5.1 mmol) and stirred for one hour at -80 °C. After warming to room temperature the pale yellow suspension was stirred for another 12 hours and the solvent was removed under reduced pressure. The white residue was recrystallized from a MeOH / CH2Cl2 / pentane mixture to give diphosphine 38 as white crystals (0.6 g, 0.9 mmol, 19 %). ¹H NMR (600 MHz, CDCl3, 300 K): δ 7.84 (m, 1H, 5-H), 7.65 (d, ³J(H,H) = 7.6 Hz, 1H, 2-H), 7.25 (vt, J = 7.4 Hz, 1H, 4-H), 7.08 (vt, J

= 7.4 Hz, 1H, 3-H), 3.26 (vt, ²J(P,H) = 5.6 Hz, 2H, 7-H), 2.02 – 1.67 (m, 60H, 9-11-H, 9’-11’-H, 13-15-H, and 13’-15’-H). ¹³C{¹H} NMR (151 MHz, CDCl3, 300 K): δ 150.1 (dd, ²J(P,C) each = 25.9 and 13.9 Hz, C6), 136.4 (d, ²J(P,C) = 2.1 Hz, C2), 133.2 (dd, ¹J(P,C) = 23.2 and ³J(P,C) = 3.5 Hz, C1), 130.9 (dd, ³J(P,C) each = 22.0 and 4.8 Hz, C5), 128.0 (s, C4), 123.1 (s, C3), 41.8 and 40.9 (d each, ²J(P,C) = 12.6 and 10.7 Hz, C9, C9’, C13, and C13’), 37.3 and 36.6 (d each, ¹J(P,C) = 24.3 and 20.6 Hz, C8, C12, C8’, and C12’), 37.0 (s, C11, C11’, C15, and C15’), 28.9 and 28.6 (d each, ³J(P,C) = 8.7 and 7.8 Hz, C10, C10’, C14, and C14’), 22.9 (dd, ¹J(P,C) = 30.6 and ³J(P,C) = 18.7 Hz, C7). ³¹P{¹H} NMR (162 MHz, CDCl3, 300 K): δ 35.9 (s, P2), 16.1 (s, P1). MS (FAB):

m/z = 556.1 (M+ - C10H15), 422.7 (M+ - 2 ´ C10H15), 389.6, 287.1. Anal Calc. (%) for [C47H66P2, CH2Cl2, MeOH]: C: 72.66, H: 8.96. Found: C: 73.11, H: 8.85.