Efficient Heterogeneous Asymmetric Transfer Hydrogenation of Ketones Using Highly Recyclable and Accessible Silica-Immobilized Ru-TsDPEN Catalysts

Article abstract of DOI:10.1021/ol036065z

(Matrix presented) Chiral Ru-TsDPEN [N-(p-toluenesulfonyl)-1,2- diphenylethylenediamine]-derived catalysts were first successfully immobilized onto amorphous silica gel and mesoporous silicas of MCM-41 and SBA-15 by an easily accessible approach. The catalyst immobilized on silica gel demonstrated remarkably high catalytic activities and excellent enantioselectivities (up to >99% ee) for the heterogeneous asymmetric transfer hydrogenation of various ketones. Particularly, the catalyst could be readily recovered and reused in multiple consecutive catalytic runs (up to 10 uses) with the completely maintained enantioselectivity.

Full text of DOI:10.1021/ol036065z

Efficient Heterogeneous Asymmetric Transfer Hydrogenation
of Ketones Using Highly Recyclable and Accessible
Silica-Immobilized Ru-TsDPEN Catalysts
Pei Nian Liu, Pei Ming Gu, Fei Wang and Yong Qiang Tu *
Department of Chemistry and State Key Laboratory of Applied Organic Chemistry
Lanzhou University, Lanzhou 730000, P. R. China.
tuyq@lzu.edu.cn
Supporting Information
1. General.
2. Synthesis of (1R,2R)-4.
3. General procedure for the synthesis of immobilized ligands 5-7.
4. Synthesis of the modified ligand 8.
5. General procedure for the transfer hydrogenation of ketones using the
immobilized catalysts.
6. Determination of the leaching of Ru from the catalyst Ru-5 in the recycling
reductions of acetophenone.
7. Analytical data for obtained chiral aromatic alcohols.
8. Reference.
1

1. General:
Fomic acid-triethylamine azeotrope was prepared by adding triethylamine to fomic acid (ratio: 2:5)
and then distilled under reduced pressure. Acetophenone was distilled from KMnO4 and CH2Cl2
was distilled from CaH2. Triethylamine was distilled and stored avoiding light. [RuCl2(p-cymene)]2
was prepared according to literature1 and (1R,2R)-TsDPEN was prepared by standard method.
Amorphous silica gel (60-100 mesh), mesoporous silicas of MCM-41 and SBA-15 were heated at
o
150 C for 3 h and cooled under argon before use. Toluene was freshly distilled from a deep-blue
solution of sodium-benzophenone under argon. Other reagents and chemicals were used as received.
1H NMR and 13C NMR spectra were recorded on Varian Mercury-plus 300 BB with TMS as
internal standard. HRMS data were measured with ESI techniques (Bruker Apex II). Elemental
analysis was performed on elementar vario EL and FT-IR spectra was performed on Nicolet
NEXUS 670. The pore sizes and surface areas were determined on Micromeritics ASAP 2010
Accelerated Surface Area and Porosimetry System. The inductively coupled plasma atomic
emission spectrometry (ICP-AES) was performed on Perkin-Elmer ICP/6500 inductively coupled
plasma spectrometer. Optical rotation values were measured on Perkin-Elmer 341 polarimeter.
Enantiomeric excess values were determined by GC with a CP-Chirasil-DEX CB column (25 m ×
0.32 mm) on Varian CP-3800 or by HPLC with Chiralcel OB or OJ column on Agilent 1100 Series.
2. Synthesis of (1R,2R)-4:
(1R,2R)-DPEN 2 (0.636 g, 3.0 mmol) and triethylamine (0.6 mL) were dissolved in CH2Cl2 (30 mL),
and 2-(4-chlorosulfonylphenyl)ethyltrimethoxysilane 3 (0.75 g, 2.31 mmol) in CH2Cl2 (30 mL) was
2

o
then added dropwise at 0 C. The reaction mixture was then allowed to warm to room temperature
slowly and stirred for 3 h. After the solvent was removed in vacuo, the residue was fast passed
through a short column (silica gel, eluent: Et3N:CH3OH:CH2Cl2 = 1:10:100) and concentrated in
vacuo to afford (R,R)-4 as beige glass.
Yield: 86%; [α]D20 -36 (c 0.8, CH2Cl2); 1H NMR (300 MHz, CDCl3) δ 0.89-0.95 (m, 2H), 1.50 (s,
2H, NH2), 2.65-2.70 (m, 2H), 3.59 (s, 9H), 4.12 (d, J = 5.4 Hz, 1H), 4.37 (d, J = 5.4 Hz, 1H),
6.99-7.34 (m, 14H); 13C NMR (75 MHz, CDCl3) δ 11.0, 28.5, 50.6, 60.4, 63.2, 126.5, 126.9,
127.3, 127.4, 127.8, 128.2, 128.3, 137.3, 139.1, 141.3, 148.8; IR 3352, 3296, 3171, 3060, 3028,
2941, 2841, 1902, 1691, 1600, 1495, 1454, 1410, 1343, 1322, 1265, 1191, 1157, 1088, 1013 cm-1;
ESI-HRMS, calcd for C25H32N2O5SSi + H+ 501.1874, found 501.1881.
3. General procedure for the synthesis of immobilized ligands 5-7:
The predried silica (3 g) and ligand (R,R)-4 (0.25 g) were added to dry toluene (40 mL) and the
mixture was refluxed for 24 h under argon. After filtration, the white solid was washed by toluene
(60 mL), mixture solvent of CH2Cl2 and CH3OH (1:1, 100 mL). Then the solid was suspended in
the mixture solvent (CH2Cl2:CH3OH = 1:1, 50 mL) and stirred overnight. After filtration and
thorough wash with the mixture solvent (CH2Cl2:CH3OH = 1:1, 50 mL) and CH3OH (50 ml), the
solid was dried at 60 oC in vacuo for 24 h to give the immobilized ligand.
Ligand 5: IR 3440, 2960, 1642, 1509, 1464, 1097, 801, 702, 559, 469 cm-1; elemental analysis: N
0.41, C 4.71, S 0.48, H 0.59; average pore size: 90.2 Å; SBET: 324 m2/g.
3

Ligand 6: IR 3442, 2962, 2860, 1627, 1461, 1081, 812, 698, 455 cm-1; elemental analysis: N 0.38,
C 6.52, S 0.47, H 1.04; pore size: 18.7 Å; SBET: 1150 m2/g.
Ligand 7: IR 3438, 2958, 2856, 1635, 1462, 1084, 811, 701, 462 cm-1; elemental analysis: N 0.28,
C 5.74, S 0.31, H 0.54; pore size: 61.8 Å; SBET: 497 m2/g.
4. Synthesis of the modified ligand 8:
Immobilized ligand 5 (0.3 g) was added to hexamethyldisiloxane (HMDSO, 10 mL) and the
mixture was refluxed for 18 h under argon. After filtration and thorough wash with CH3OH (30 mL),
the solid was dried at 60 oC in vacuo for 24 h to give ligand 8.
Ligand 8: IR 3439, 2970, 2845, 1637, 1460, 1095, 965, 802, 700, 467 cm-1; elemental analysis: N
0.33, C 5.55, S 0.41, H 1.10; average pore size: 87.4 Å; SBET: 313 m2/g.
5. General procedure for the transfer hydrogenation of ketones using the
immobilized catalysts:
Immobilized ligand (0.0068 mmol), [RuCl2(p-cymene)]2 (0.002 mmol) and triethylamine (0.016
mmol) were stirred in dry CH2Cl2 (0.4 mL) for 1 h under argon at 28 °C. Then the formic
acid-triethylamine azeotrope (0.2 mL) and the ketone (0.4 mmol) were added and the mixture was
stirred at 40 °C and monitored by TLC. After the completion of the reaction, dry CH2Cl2 (1 mL)
was added and the mixture was stirred for 1 min, then the reactor was centrifuged (2000 r/min) for
1-2 min and the solution was removed with syringe. The catalyst was then washed with CH2Cl2 (1
mL) twice and CH2Cl2 was removed; a new reaction could be conducted by adding formic
4

acid-triethylamine azeotrope (0.2 mL) and ketone (0.4 mmol) in turn to the recovered catalyst. The
solution containing the product was fast passed through a short column (silica gel, eluent: Et2O) and
the conversion and the ee value were then determined by chiral GC on CP-Chirasil-DEX CB
column (25 m × 0.32 mm) or by HPLC with Chiralcel OB or OJ column on Agilent 1100 Series.
6. Determination of the leaching of Ru from the catalyst Ru-5 in the recycling
reductions of acetophenone.
The predried recovered catalyst Ru-5 (50.0 mg) with the powder mixture of KOH (1.0 g) and KNO3
(0.2 g) was heated to 650 oC for 5-10 min, then cooled, dissolved in hot water and added 12 M HCl
(4 mL) to acidify the solution, then the solution was diluted to 50.0 mL and the amount of metal Ru
was determined by ICP-AES.
The leached Ru in organic solutions after the reaction was dissolved in 0.3 M HCl (10 mL) and
determined by ICP-AES.
Ru/SiO2 (weight): before use: 0.54%, after 5 uses: 0.35%.
Amount of leached Ru in organic solutions: after the 1st run: 11 µg, after the 2nd run: 15 µg, after
the 3rd run: 17 µg, after the 4th run: 24 µg, after the 5th run: 34 µg.
7. Analytical data for obtained chiral aromatic alcohols:
OH
C8H10O, FW = 122.16
5

[α]D28 +52 (c 1.1, CHCl3); 1H NMR (300 MHz, CDCl3, 97% ee) δ 1.45 (d, J = 6.6 Hz, 3H), 2.29
13
(s, 1H, OH), 4.80-4.86 (m, 1H), 7.23-7.35 (m, 5H); C NMR (75 MHz, CDCl3) δ 25.0, 70.2,
125.3, 127.3, 128.4, 145.8; GC analysis: CP-Chirasil-DEX CB column (25 m × 0.32 mm), column
o
o
temprature = 126 C, (isothemal), injector temprature = 250 C, detector temperature (FID) =300,
carrier gas: N2, inlet pressure = 7 psi; tR = 8.1 min, tS = 8.8 min.
OH
F
C8H9FO, FW = 140.15
[α]D28 +36 (c 1.8, CHCl3, 94% ee); 1H NMR (300 MHz, CDCl3) δ 1.42-1.45 (m, 3H), 2.69 (s, 1H,
13
OH), 4.78-4.85 (m, 1H), 6.89-6.96 (m, 1H), 7.03-7.09 (m, 2H), 7.23-7.31 (m, 1H); C NMR (75
MHz, CDCl3) δ 25.1, 69.6, 112.1, 112.4, 113.9, 114.2, 120.9, 129.8, 129.9, 148.4, 148.5, 161.3,
164.5; GC analysis: CP-Chirasil-DEX CB column (25 m × 0.32 mm), column temprature = 135 oC,
o
(isothemal), injector temprature = 250 C, detector temperature (FID) =300, carrier gas: N2, inlet
pressure = 7 psi;tR = 8.6 min, tS = 9.6 min
OH
F
C8H9FO, FW = 140.15
[α]D28 +38 (c 1.2, CHCl3, 93% ee); 1H NMR (300 MHz, CDCl3) δ 1.53 (d, J = 6.6 Hz, 3H), 2.20
(s, 1H, OH), 4.96-5.03 (m, 1H), 7.43-7.47 (m, 2H), 7.75-7.80 (m, 2H); 13C NMR (75 MHz, CDCl3)
δ 25.0, 70.4, 123.8, 125.7, 126.1, 127.6, 127.9, 128.2, 132.8, 133.3, 143.2; GC analysis:
CP-Chirasil-DEX CB column (25 m × 0.32 mm), column temprature = 127 oC, (isothemal), injector
o
temprature = 250 C, detector temperature (FID) =300, carrier gas : N2, inlet pressure = 7 psi; tR =
9.7 min, tS = 10.5 min.
6

OH
Cl
C8H9ClO, FW = 156.61
[α]D28 +54 (c 2.3, CHCl3, 94% ee); 1H NMR (300 MHz, CDCl3) δ 1.42-1.45 (m, 3H), 2.78 (s, 1H,
13
OH), 5.22-5.26 (m, 1H), 7.12-7.30 (m, 3H), 7.53-7.55 (m, 1H); C NMR (75 MHz, CDCl3) δ
23.4, 66.7, 126.3, 127.1, 128.2, 129.2, 131.4, 143.0; GC analysis: CP-Chirasil-DEX CB column (25
o
o
m × 0.32 mm), column temprature = 160 C, (isothemal), injector temprature = 250 C, detector
temperature (FID) =300, carrier gas: N2, inlet pressure = 7 psi; tR = 7.2 min, tS = 7.8 min.
OH
Br
C8H9BrO, FW = 201.06
[α]D28 +48 (c 1.7, CHCl3, 93% ee); 1H NMR (300 MHz, CDCl3) δ 1.42 (d, J = 6.3 Hz, 3H), 2.81
(s, 1H, OH), 5.14-5.20 (m, 1H), 7.08 (t, J = 7.5 Hz, 1H), 7.30 (t, J = 7.2 Hz, 1H), 7.45-7.54 (m, 2H);
13C NMR (75 MHz, CDCl3) δ 23.5, 69.0, 121.5, 126.6, 127.7, 128.6, 132.5, 144.6; GC analysis:
CP-Chirasil-DEX CB column (25 m × 0.32 mm), column temprature = 170 oC, (isothemal), injector
o
temprature = 250 C, detector temperature (FID) =300, carrier gas: N2, inlet pressure = 7 psi; tR =
6.5 min, tS = 7.3 min.
OH
OCH3
C9H12O2, FW = 152.19
[α]D28 +39 (c 1.0, CHCl3, 96% ee); 1H NMR (300 MHz, CDCl3) δ 1.48 (d, J = 6.3 Hz, 3H), 2.02
(s, 1H, OH), 3.81 (s, 3H), 4.82-4.88 (m, 1H), 6.79-6.82 (m, 1H), 6.92-6.95 (m, 2H), 7.25 (t, J = 8.4
Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 25.1, 55.2, 70.3, 110.9, 112.9, 117.7, 129.5, 147.6, 159.8;
o
GC analysis: CP-Chirasil-DEX CB column (25 m × 0.32 mm), column temprature = 146 C,
o
(isothemal), injector temprature = 250 C, detector temperature (FID) =300, carrier gas: N2, inlet
7

pressure = 7 psi; tR = 11.0 min, tS = 11.7 min.
OH
C10 H12O, FW = 148.20
[α]D28 -32 (c 1.0, CHCl3); 1H NMR (300 MHz, CDCl3, >99% ee) δ 1.26-1.99 (m, 4H), 2.71-2.84
(m, 2H), 4.75 (t, J = 4.2 Hz, 1H), 7.07-7.10 (m, 1H), 7.16-7.23 (m, 2H), 7.39-7.42 (m, 1H); 13C
NMR (75 MHz, CDCl3) δ 18.8, 29.2, 32.2, 68.1, 126.1, 127.5, 128.6, 128.9, 137.0, 138.8; HPLC
analysis: Chiralcel OB column, 2-propanol:hexane = 2.2:97.8 (1.0 mL/min), tR = 11.3 min, tS = 16.6
min.
OH
C9H10O, FW = 134.18
o
28
1
Mp: 69-70 C; [α]D -31 (c 1.3, CHCl3, >99% ee); H NMR (300 MHz, CDCl3) δ 1.87 (s, 1H,
OH), 1.90-1.99 (m, 1H), 2.42-2.53 (m, 1H), 2.76-2.86 (m, 1H), 3.00-3.10 (m, 1H), 5.23 (s, 1H),
13
7.22-7.25 (m, 3H), 7.39-7.42 (m, 1H); C NMR (75 MHz, CDCl3) δ 29.8, 35.9, 76.4, 124.2,
124.9, 126.7, 128.3, 143.3, 145.0. HPLC analysis: Chiralcel OB column, 2-propanol:hexane = 5:95
(1.0 mL/min), tR = 8.4 min, tS = 12.1 min.
OH
C12H12O, FW = 172.22
o
28
1
Mp: 68-70 C; [α]D +46 (c 1.1, CHCl3, 95% ee); H NMR (300 MHz, CDCl3) δ 1.47-1.50 (m,
3H), 2.28(s, 1H, OH), 5.13-5.19 (m, 1H), 6.95-7.03 (m, 1H), 7.09-7.26 (m, 4H), 7.43-7.48 (m, 2H);
13C NMR (75 MHz, CDCl3) δ 23.9, 64.4, 115.1, 115.3, 124.3, 126.6, 128.6, 128.7, 130.9, 132.5,
158.0, 161.4; HPLC analysis: Chiralcel OJ column, 2-propanol:hexane = 7:93 (1.0 mL/min), tS =
18.6 min, tR = 23.8 min.
8

OH
O
C6H8O2, FW = 112.13
28
1
[α]D +9 (c 1.4, CHCl3, 96% ee); H NMR (300 MHz, CDCl3) δ 1.54 (d, J = 6.6 Hz, 3H),
13
4.85-4.91 (m, 1H), 6.23 (d, J = 3 Hz, 1H), 6.32-6.33 (m, 1H), 7.37 (d, J = 1.2 Hz, 1H); C NMR
(75 MHz, CDCl3) δ 21.2, 63.6, 105.1, 110.1, 141.9, 157.6; GC analysis: CP-Chirasil-DEX CB
column (25 m × 0.32 mm), column temprature: 60 oC hold 0.1 min, ramp 3/min to 87 oC hold 3 min,
o
injector temprature = 250 C, detector temperature (FID) =300, carrier gas: H2, inlet pressure = 7
psi; tR = 9.8 min, tS = 10.4 min.
OH
CN
C9H9NO, FW = 147.17
[α]D28 +58 (c 1.1, CHCl3, 97% ee); 1H NMR (300 MHz, CDCl3) δ 2.69 (d, J = 6.0 Hz, 2H), 3.17
(s, 1H, OH), 4.96 (t, J = 6.0 Hz, 1H), 7.30-7.40 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 27.8, 69.8,
117.4, 125.5, 128.6, 128.8, 141.0; HPLC analysis: Chiralcel OJ column, 2-propanol:hexane = 10:90
(1.0 mL/min), tS = 22.0 min, tR = 26.5 min.
8. Reference: (1) Bennett, M. A.; Smith, A. K. J. Chem. Soc., Dalton Trans., 1974, 233.
9