Organometallics
Article
+
+
JHH = 8.5 Hz, 1H, quin-H3), 7.36−7.28 (m, 2H, quin-H4, quin-H6),
.06 (d, J = 7.1 Hz, 1H, quin-H5), 3.58 (q, J = 7.0 Hz, 4H,
HRMS (FT-ICR-MS): [(C H N P)(CO)(H)Ru] ([M − Cl] ) m/
20
31
2
7
z
= 461.129021, m/z = 461.12957.
HH
HH
(found)
(calcd.)
N(CH CH ) ), 3.21 (d, J = 2.9 Hz, 2H, CH P), 1.83 (qd, J =
Synthesis of (CO)(H)(QNP′)ruthenium(II) (1Q). In a nitrogen-filled
2
3
2
PH
2
HH, PH
7
.1, 2.0 Hz, 2H, P(CH(CH ) ) ), 1.16 (t, J = 7.0 Hz, 6H), 1.09 (t,
glovebox, 39 mg (0.074 mmol) of 1QCl was dissolved in 2 mL of
THF in a 20 mL screw-capped vial. The solution was cooled to −35
3
2
2
HH
JHH = 6.9 Hz, 6H, N(CH CH ) ), 1.05 (dd, J = 8.8, 7.1 Hz, 6H,
2
3
2
PH, HH
t
P(CH(CH ) ) ).
°C, and 8 mg (0.074 mmol) of KO Bu was added. The resulting dark
3
2 2
Synthesis of (CO)(Cl)(H)(QNP)ruthenium(II) (1QCl). In a nitrogen-
filled glovebox, 50 mg (0.14 mmol) of QNP ligand and 130 mg (0.14
mmol) of Ru(PPh ) (H)(CO)(Cl) was mixed together in 4 mL of
red solution was stirred at −35 °C for 4 h. Afterward, the reaction was
filtered and the resulting filtrate was concentrated in vacuo to ∼0.5
mL. Petroleum ether (2 mL) was added and the resulting black solid
was filtered off and discarded. The red filtrate was concentrated in
3
3
THF in a 25 mL sealed pressure vessel. The solution was stirred at 65
C for 16 h, after which the reaction was filtered and the resulting
3
1
1
°
vacuo to yield 29 mg (81%) of product. P{ H} NMR (121 MHz,
1
filtrate concentrated in vacuo to ∼0.5 mL. Diethyl ether (2 mL) was
added, and the resulting yellow/orange solid was collected on a glass-
fritted funnel and washed with ether (3 × 5 mL) to yield 44 mg
C D ): δ, ppm 98.7 (s). H NMR (300 MHz, C D ): δ, ppm 6.74
7
8
7
8
(dd, JHH = 5.4, 3.3 Hz, 1H, quin-H7), 6.49 (s, 1H, quin-H3), 6.49 (s,
1H, quin-H5), 6.41 (d, JHH = 2.0 Hz, 1H, quin-H6), 6.39 (s, 1H, quin-
H4), 3.86 (d, JHH = 2.3 Hz, 1H, CHP), 3.57−3.43 (m, 1H,
N(CHHCH ) ), 3.24−3.08 (m, 1H, N(CHHCH ) ), 2.77 (dddd, J
(
60%). Crystals suitable for diffraction or further purification was
obtained by recrystallization from DCM with diethyl ether diffusion.
3
a
3
a
HH
3
1
1
1
P{ H} NMR (121 MHz, CDCl ): δ, ppm 111.04 (d, J = 14.3 Hz).
= 11.7, 8.9, 7.0, 3.8 Hz, 2H, N(CH CH ) ), 1.32 (d, J = 11.5 Hz,
3
PH
2 3 b PH
H NMR (300 MHz, CDCl ): δ, ppm 8.10 (d, J = 8.7 Hz, 1H, quin-
9H, P(C(CH ) ) ), 1.28 (d, J = 12.0 Hz, 9H, P(C(CH ) ) ), 1.07
3 3 a PH 3 3 a
3
H7), 7.69 (ddd, JHH = 7.6, 6.3, 1.2 Hz, 2H, quin-H3, quin-H5), 7.59−
(t, JHH = 7.0 Hz, 3H, N(CH
N(CH CH ), −25.02 (d, JPH = 27.7 Hz, 1H). FTIR-ATR: 1897
cm (νCO).
2 3 a
CH ) ), 0.50 (t, JHH = 7.2 Hz, 3H,
7
3
1
.47 (m, 2H, quin-H4, quin-H6), 4.37−4.24 (m, 1H, N(CHHCH ) ),
2
)
3 b
3
a
−
1
.95−3.70 (m, 2H, CHHP, N(CHHCH ) ), 3.60 (dd, J
= 16.6,
= 12.2, 7.0, 2.4 Hz, 1H,
3
a
PH, HH
Ph
Ph
0.9 Hz, 1H, CHHP), 3.24 (ddd, J
Synthesis of (CO)(H)(QNP′ )ruthenium(II) (1Q ). The synthesis
HH
Ph
N(CHHCH ) ), 3.09−2.96 (m, 1H, N(CHHCH ) ), 1.78 (t, J
=
of 1Q followed the same procedure as that for 1Q, and 10 mg
3
b
3
b
HH
7
.0 Hz, 3H, N(CH CH ) ), 1.49 (d, J = 13.7 Hz, 9H,
(71%) (15 mg, 0.02 mmol scale) of product was recovered as a dark
2
3
a
PH
3
1
1
P(C(CH ) ) ), 1.22 (d, J = 13.1 Hz, 9H, P(C(CH ) ) ), 1.05 (t,
red residue. P{ H} NMR (121 MHz, C D ): δ, ppm 61.41 (d, J
=
3
3
a
PH
3
3
b
7
8
PH
1
JHH = 7.0 Hz, 3H, N(CH CH ) )), −15.19 (d, J = 25.9 Hz, 1H).
12.9 Hz). H NMR (300 MHz, C D ) δ, ppm 7.95−7.83 (m, 2H,
2
3
b
PH
7
8
−1
FTIR-ATR: 1882 cm (ν ). HRMS (FT-ICR-MS): [(C H N P)-
P(o-C H ) ), 7.85−7.73 (m, 2H, P(o-C H ) ), 7.13−6.93 (m, 7H,
CO
22 35
2
6
5
a
6
5 b
+
+
(
4
CO)(H)Ru] ([M − Cl] ) m/z
= 489.160321, m/z(calcd.)
=
P(m-C H ) , (p-C H ) , quin-H7), 6.81 (dd, J = 6.4, 2.1 Hz, 1H,
(
found)
6 5 2 6 5 2
89.16087.
quin-H4), 6.62 (s, 1H, quin-H3), 6.51−6.41 (m, 2H, quin-H6, quin-
H5), 4.33 (d, J = 2.5 Hz, 1H, CHP), 3.53 (p, J = 8.1, 7.3 Hz, 1H,
Ph
Ph
Synthesis of (CO)(Cl)(H)(QNP )ruthenium(II) (1Q Cl). In a
nitrogen-filled glovebox, 64 mg (0.18 mmol) of QNP ligand and
70 mg (0.179 mmol) of Ru(PPh ) (H)(CO)(Cl) were mixed in 4
PH
HH
Ph
N(CHHCH ) ), 3.12 (dt, J = 14.1, 7.0 Hz, 1H, N(CHHCH ) ),
3 a HH 3 a
1
2.86 (td, JHH = 7.3, 3.6 Hz, 2H, N(CH CH ) ), 0.96 (t, J = 7.0 Hz,
2 3 b HH
3
3
mL of THF in a 25 mL sealed pressure vessel. The solution was
stirred at 65 °C for 12 h, after which the reaction was filtered. The
resulting orange solid was collected on a glass-fritted funnel and
washed with ether (3 × 5 mL) to yield 64 mg (63%) of a bright
orange solid. Crystals suitable for diffraction were grown by layering a
3H, N(CH CH ) ), −0.01 (t, J = 7.2 Hz, 3H, N(CH CH ) ),
2
3
a
HH
2
3 b
−22.70 (d, J = 34.0 Hz, 1H, RuH).
Synthesis of Isoquinoline-Derived Compounds. Synthesis of
1-Bromomethyl-3-methylisoquinoline and 3-Bromomethyl-1-
methylisoquinoline. An argon-filled 250 mL two-necked round-
bottomed flask equipped with a condenser was charged with 600 mg
3
1
1
DCM solution under hexane. P{ H} NMR (121 MHz, CDCl ): δ,
3
1
ppm 74.51 (s). H NMR (400 MHz, CDCl ): δ, ppm 8.16 (d, J
=
=
(3.82 mmol) of 1,3-dimethylisoquinoline, 50 mL of CCl , 687 mg
4
3
HH
8
8
.6 Hz, 1H, quin-H7), 8.01−7.93 (m, 2H, P(o-C H ) ), 7.75 (d, J
(3.82 mmol) of NBS, and 93 mg (0.382 mmol) of benzoyl peroxide.
The resulting mixture was stirred at 80 °C overnight. Afterward, the
reaction was cooled to room temperature, and a tan solid was filtered
off open to air. The filtrate was concentrated in vacuo and redissolved
6
5
a
HH
.2 Hz, 1H, quin-H5), 7.72 (d, J = 7.4 Hz, 1H, quin-H4), 7.59 (t,
HH
JHH = 8.9 Hz, 1H, quin-H6), 7.56 (d, JHH = 7.8 Hz, 1H, quin-H3),
7
.51−7.45 (m, 2H, P(o-C H ) ), 7.43−7.40 (m, 3H, P(m-C H ) ,
6
5
b
6
5 a
P(p-C H ) ), 7.33−7.31 (m, 3H, P(m-C H ) , P(p-C H ) ), 4.59 (dd,
in 100 mL of benzene. This solution was washed with NaHCO
50 mL) and brine (3 × 50 mL), and was dried over Na
3
(3 ×
6
5
a
6
5
b
6
5 b
J
= 9.7, 18.4 Hz, 1H, CHHP), 4.40 (dd, J
= 12.2, 17.5 Hz,
2
SO
4
.
PH, HH
PH, HH
1
H, CHHP), 4.26 (ddd, JHH = 7.0, 11.8, 14.3 Hz, 1H,
Concentration in vacuo gave a dark orange oil with a roughly 50:50
mixture of each monobrominated isomer. Separation of the 3-bromo
product was achieved using column chromatography (10% ethyl
N(CHHCH ) ), 3.81 (td, J = 7.0, 19.5 Hz, 1H, N(CHHCH ) ),
3
a
HH
3 a
3
.35−3.23 (m, 1H, N(CHHCH ) ), 3.14−3.04 (m, 1H, N-
3
b
(CHHCH ) ), 1.83 (t, J = 6.4 Hz, 3H, N(CH CH ) ), 1.09 (t,
acetate in hexanes). 1-Bromomethyl-3-methylisoquinoline (136 mg,
3
b
HH
2
3 a
1
JHH = 6.8 Hz, 3H, N(CH CH ) ), −14.14 (d, J = 26.0 Hz, 1H,
RuH). FTIR-ATR: 1909 cm
15%). H NMR (300 MHz, CDCl
): δ, ppm 8.20 (d, JHH = 8.4 Hz,
3
2
3
b
PH
−
1
(ν ). HRMS (FT-ICR-MS):
1H, isoquin-H8), 7.77 (d, JHH = 8.0 Hz, 1H, isoquin-H5), 7.69−7.64
(m, 1H, isoquin-H6), 7.64−7.55 (m, 1H, isoquin-H7), 7.47 (s, 1H,
isoquin-H4), 5.02 (s, 2H, CH Br), 2.69 (s, 3H, isoquin−CH ). 3-
CO
+
+
[
(C H N P)(CO)(H)Ru] ([M − Cl] ) m/z
= 529.09746,
26
27
2
(found)
m/z(
= 529.09772.
calcd.)
2
3
iPr
iPr
iPr
1
Synthesis of (CO)(Cl)(H)(QNP )ruthenium(II) (1Q Cl). 1Q Cl
was synthesized using the same procedure as used for 1QCl.
Purification was achieved via recrystallization from DCM with diethyl
ether layering to yield 38 mg (44%) of product. P{ H} NMR (121
MHz, CDCl ): δ, ppm 100.80 (s). H NMR (300 MHz, CDCl ): δ,
Bromomethyl-1-methylisoquinoline (163 mg, 18%). H NMR (300
MHz, CDCl ): δ, ppm 8.12 (d, J = 8.2 Hz, 1H, isoquin-H8), 7.79
3
HH
(d, JHH = 8.7 Hz, 1H, isoquin-H5), 7.67 (dt, JHH = 8.1, 1.2 Hz, 1H,
isoquin-H6), 7.63 (s, 1H, isoquin-H4), 7.59 (d, JHH = 6.9 Hz, isoquin-
H7), 4.70 (s, 2H, CH Br), 2.97 (s, 3H, isoquin-CH ).
3
1
1
1
3
3
2
3
ppm 8.09 (d, JHH = 8.4 Hz, 1H, quin-H7), 7.71 (d, JHH = 7.8 Hz, 1H,
quin-H3), 7.69 (d, JHH = 7.2 Hz, 1H, quin-H4) 7.55 (t, JHH = 7.8 Hz,
Synthesis of N-Ethyl-N-((1-methylisoquinolin-3-yl)methyl)-
ethanamine. To a 50 mL round-bottomed flask open to air was
charged 10 mL of THF and 120 mg (0.508 mmol) of the bromo
methyl isoquinoline. The solution was then cooled to 0 °C before
0.12 mL (1.12 mmol) of diethylamine was added dropwise. The
solution was stirred overnight and allowed to slowly warm to room
temperature. The resulting suspension was concentrated in vacuo, and
50 mL of diethyl ether was added. This solution was washed with 3 ×
15 mL 1 M NaOH and 3 × 15 mL saturated brine, and the combined
organic layers were dried over Na SO . Concentration in vacuo
1
1
H, quin-H6), 7.48 (d, JHH = 8.5 Hz, 1H, quin-H5), 4.16 (dq, JHH
=
1.4, 7.2 Hz, 1H, N(CHHCH ) ), 3.84 (m, 2H, N(CHHCH ) ,
3
a
3 a
CHHP), 3.60 (dd, JHH = 17.2, 10.5 Hz, 1H, CHHP), 3.26 (m, 1H,
N(CHHCH ) ), 3.11−2.86 (m, 2H, N(CHHCH ) , P-
3
b
3 b
(
(
CH(CH ) ) ), 2.17 (dp, J
= 11.3, 6.7 Hz, 1H), P-
3
2
a
PH, HH
CH(CH ) ) , 1.79 (t, J = 7.0 Hz, 3H, N(CH CH ) ), 1.51 (dd,
3
2
b
HH
2
3 a
JHH = 17.0, 7.4 Hz, 3H, P(CH(CH ) ) ), 1.32 (dd, J = 12.4, 7.2 Hz,
3
a
a
HH
3
H, P(CH(CH ) ) ), 1.19−1.03 (m, 6H, P(CH(CH ) ) , N-
3
b
a
3
a
b
2
4
(CH CH ) ), 0.85 (dd, J
= 15.3, 6.8 Hz, 3H, P(CH(CH ) ) ),
provided mostly pure material, which was purified through column
chromatography (75% ethyl acetate, hexanes) to give 53 mg (46%) of
2
3
b
PH, HH
3 b b
−
1
−
14.81 (d, JPH = 23.6 Hz, 1H, RuH). FTIR-ATR: 1889 cm (νCO).
M
Organometallics XXXX, XXX, XXX−XXX