112
G. Kang et al. / Catalysis Communications 57 (2014) 111–114
water-soluble ligands for Rh(III)-catalyzed ATH of aromatic ketones
in pure water with a substrate to catalyst (S/C) ratio of 500 and only
the use of 1.5 equiv. of hydride donor HCO2Na.
2.4. Synthesis of TsDPENs 5b
Compound 5b was synthesized using the same procedure as that
used for 5a, yield: 75%; [α]2D3 = −64.9 (c = 0.8, CH3OH); 1H NMR
(400 MHz, CD3OD): δ 7.64 (d, J = 2.0 Hz, 1H), 7.56–7.53 (m, 2H), 7.41
(d, J = 2.0 Hz, 1H), 7.17–7.12 (m, 7H), 6.88–6.77 (m, 5H), 5.35 (s, 2H),
4.57 (d, J = 10.0 Hz, 1H), 4.30 (d, J = 10.0 Hz, 1H), 4.18 (t, J = 7.6 Hz,
2H), 2.57 (s, 3H), 1.85–1.76 (m, 2H), 1.42–1.35 (m, 2H), 0.97 (t, J =
7.6 Hz, 3H); 13C NMR (100 MHz, CD3OD): δ 146.6, 143.5, 140.1, 139.3,
139.0, 130.4, 130.2, 129.9, 129.8, 129.7, 129.3, 123.8, 65.8, 62.2, 52.7,
2. Experimental
2.1. Material and instruments
All commercially available chemicals and solvents were used as re-
ceived. NMR spectra were obtained at 400 MHz (1H NMR) and
100 MHz (13C NMR). Chemical shifts are reported in ppm relative to
the internal standard of TMS. All the compounds synthesized (shown
in Table 2) in the manuscript are known compounds. Their absolute
configurations of the products were determined by comparison with
the known optical rotation and chiral HPLC analysis. HPLC analysis
was performed using ChiralPak columns.
50.3, 33.6, 21.4, 14.7, 11.1; HRMS (ESI) calcd for [C29H35N4O2S]+
503.2481, found: 503.2483.
:
2.5. Synthesis of TsDPENs 5c
Compound 5c was synthesized using the same procedure as that
used for 5a, yield: 63%; [α]2D3 = −51.8 (c = 0.6, CH3OH); 1H NMR
(400 MHz, CD3OD): δ 7.63–7.55 (m, 3H), 7.46–7.32 (m, 6H), 7.20–7.11
(m, 7H), 6.76–6.75 (m, 5H), 5.43 (s, 2H), 5.35 (s, 2H), 4.63 (d, J =
10.4 Hz, 1H), 4.41 (d, J = 10.4 Hz, 1H), 2.56 (s, 3H); 13C NMR
(100 MHz, CD3OD): δ 147.0, 143.3, 140.1, 138.0, 137.2, 135.8, 131.3,
131.0, 130.8, 130.6, 130.0, 129.9, 129.8, 129.5, 124.2, 124.1, 64.8, 61.7,
53.8, 52.8, 11.5; HRMS (ESI) calcd for [C32H33N4O2S]+: 537.2319,
found: 537.2326.
2.2. (S,S)-N-Boc-N′-(4-bromomethylphenylsulfonyl)-1,2-diphenylethyle-
nediamine 3
To a solution of (S,S)-N-Boc-1,2-diphenylethylenediamine 1 (1.87 g,
6.0 mmol) and Et3N (0.84 mL, 6.0 mmol) in dry CH2Cl2 (20 mL) cooled
in an ice-bath was added dropwise 4-bromomethylphenylsulfonyl chlo-
ride 2 (1.94 g, 7.2 mmol) in CH2Cl2 (10 mL). After the ice-bath was re-
moved, the reaction mixture was stirred at room temperature for 2 h.
Water was added to the reaction mixture. The organic phase was sepa-
rated and the aqueous phase was extracted with CH2Cl2 (2 × 20 mL),
combined with the organic phase and dried over Na2SO4. After concen-
tration, the solid was purified by flash chromatography on silica gel
(hexane/ethyl acetate = 4:1 to ethyl acetate) to afford the product 3
(2.65 g, 81%). 1H NMR (400 MHz, CDCl3): δ 7.43 (d, J = 8.0 Hz, 2H),
7.20–7.13 (m, 5H), 6.98–6.92 (m, 5H), 6.72 (d, J = 8.0 Hz, 2H), 6.31 (s,
1H), 5.18 (s, 1H), 4.77 (dd, J = 10.0 and 8.0 Hz, 1H), 4.61 (dd, J = 10.0
and 6.8 Hz, 1H), 4.35 (s, 2H), 1.47 (s, 9H); 13C NMR (100 MHz, CDCl3):
δ 157.1, 141.6, 141.3, 140.7, 137.8, 137.4, 137.3, 129.0, 128.6, 128.5,
128.0, 127.6, 127.5, 127.4, 127.3, 127.2, 80.8, 64.4, 60.1, 44.9, 31.6,
28.3. This intermediate was used for the next step without further
characterization.
2.6. Synthesis of TsDPENs 5d
Compound 5d was synthesized using the same procedure as that
used for 5a, yield: 71%; [α]2D3 = −59.6 (c = 0.8, CH3OH); 1H NMR
(400 MHz, CD3OD): δ 7.61 (d, J = 2.0 Hz, 1H), 7.48 (d, J = 8.4 Hz, 2H),
7.36 (d, J = 2.0 Hz, 1H), 7.17 (d, J = 8.4 Hz, 2H), 7.10–7.01 (m, 5H),
6.89–6.82 (m, 3H), 6.75 (d, J = 6.8 Hz, 2H), 5.43 (s, 2H), 4.85 (s, 2H),
4.40 (d, J = 8.8 Hz, 1H), 4.00 (d, J = 8.8 Hz, 1H), 3.95 (s, 3H); 13C
NMR (100 MHz, CD3OD): δ 147.6, 143.8, 142.7, 140.5, 140.0, 130.1,
130.0, 129.7, 129.5, 129.2, 128.9, 125.8, 124.0, 67.5, 63.0, 53.3, 52.8,
36.8; HRMS (ESI) calcd for [C26H29N4O3S]+: 477.1961, found: 477.1963.
2.7. General procedure for asymmetric transfer hydrogenation
To a solution of ligand 5d (2.1 mg, 0.004 mmol) in water (1 mL) was
added [Cp*RhCl2]2 (1.2 mg, 0.002 mmol), HCO2Na (41 mg, 3.0 mmol),
and ketone (2.0 mmol). The reaction mixture was stirred at room tem-
perature for the time as indicated in Tables 1 and 2. The reaction
2.3. Typical procedure for the synthesis of imidazolium ion tethered
TsDPENs 5a
Table 1
Optimization of reaction conditions for the asymmetric hydrogenation of acetophenone.a
A solution mixture of the intermediate 3 (818 mg, 1.5 mmol) and
1,2-dimethyl imidazole (173 mg, 1.8 mmol) in acetonitrile (2 mL) was
heated at 70 °C for 30 h. The solvent was removed under reduced pres-
sure, and the residue was washed with a mixture solvent (hexane/ethyl
acetate = 10:1) and dried in vacuo to give an intermediate 4a, to which
HCl solution (3 mL, 4 M in dioxane) was added. The reaction mixture
was stirred at room temperature for 5 h and the precipitation was fil-
tered and washed with hexane to give the Boc deprotected intermedi-
ate, which was used for the next step directly without further
characterization.
The Boc deprotected intermediate was subsequently neutralized by
Na2CO3 (159 mg, 1.5 mmol) in MeOH (2 mL). The mixture was stirred
for 5 h and the solvent was removed to dryness. The solid residue was
dissolved in dry CH2Cl2 and filtered, and concentrated to give the prod-
uct 5a as a white solid (550 mg, 68% yield for 2 steps). [α]2D3 = −68.4
(c = 0.8, CH3OH); 1H NMR (400 MHz, CD3OD): δ 7.60–7.55 (m, 3H),
7.40–7.38 (m, 1H), 7.20–7.14 (m, 7H), 6.90–6.80 (m, 5H), 5.36 (s, 2H),
4.68 (d, J = 10.4 Hz, 1H), 4.50 (d, J = 10.4 Hz, 1H), 3.86 (s, 3H), 2.56
(s, 3H); 13C NMR (100 MHz, CD3OD): δ 145.1, 140.9, 138.0, 135.6,
134.4, 128.5, 127.8, 127.6, 122.7, 121.2, 62.3, 59.4, 50.4, 34.4, 8.7;
HRMS (ESI) calcd for [C26H29N4O2S]+: 461.2011, found: 461.2013.
Entry
Catalyst
Ligand
T (h)
Conversion (%)b
ee (%)c
1
2
3
4
5
6
7
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[RuCl2(p-cymene)]2
[Cp*IrCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
5a
5b
5c
5d
TsDPEN
5d
5d
5d
5d
14
9
10
7
25
72
72
11
8
100
100
100
100
100
94
96
97
97
97
96
95
94
96
96
96
97
8d
9d,e
10f
100
100
18
5d
36
a
Reactions performed on a 2 mmol scale at room temperature in 1.5 mL H2O.
Determined by 1H NMR.
Determined by HPLC analysis.
1.5 equiv. of HCO2Na was used.
1.0 mL H2O was used.
b
c
d
e
f
The second run, 2 mmol HCO2H was added to regenerate HCO2Na.