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MCM-41-supported norephedrine ligand for ruthenium-catalyzed asymmetric transfer hydrogenation of ketones
Studies in Surface Science and Catalysis 146 Park et al (Editors) © 2003 Elsevier Science B.V. All rights reserved
509
MCM-41-supported norephedrine ligand for ruthenium-catalyzed asymmetric transfer hydrogenation of ketones Myung-Jong Jin, Sang-Han Kim, Sang-Joon Lee, and Wha-Seung Ahn School of Chemical Science & Engineering, Inha University, Inchon, 402-751, Korea Optically active norephedrine was anchored on MCM-41 silica material. The insoluble system was utilized as an enantioselective ligand in the asymmetric transfer hydrogenation of ketones. This reaction provided (/?)-secondary alcohols with satisfactory enantioselectivities (up to 95% ee) in good conversion. The results are comparable to those of the analogous homogeneous counterpart. 1. INTRODUCTION Transition metal complex-catalyzed asymmetric transfer hydrogenation of ketones is an attractive method for the synthesis of optically active secondary alcohols.'"^ Efficient chiral ligands have been developed for the homogeneous catalysis. Successful development of homogeneous ligands has been sometimes followed by attempts to attach the ligands on an insoluble polymeric support. This strategy offers practical advantages such as simplified separation, easy recovery of catalyst, and potential reuse.^'^ Polystyrene resin, silica gel and alumina have been most commonly used as supports for the immobilization of the ligands. Recently, mesoporous molecular sieves MCM materials with large uniform pore diameters and high specific surface areas have become of high interest as inorganic supports.'^ Our interest in the field led to prepare a new MCM-41 silica-supported norephedrine ligand 3. Herein, we describe the application of the supported ligand for the asymmetric transfer hydrogenation of ketones. Scheme I Mq,
(—^" MCM-41 —OH 1
i •
|—^\ ^ w x r~^7^' C' 2
ii
?h
|^ 3
i) (McO)3Si(CH2)3Cl, toluene, reflux ii) (+)-norcphcdrinc - EtjN, toluene, reflux 2. EXPERIMENTAL 2.1. Preparation of MCM-41 silica 1. MCM-41 silica 1 was prepared according to the literature method using surfactant Ci6H33N(CH3)3Br as the template.'^ 2.2. Preparation of 3-chIoropropyl MCM 2. To a solution of 3-(chloropropyl)trimethoxysilane (0.72 g, 3.6 mmol) in toluene (10 mL)
510
was added MCM-41 silica (1.0 g). The mixture was gradually heated to 110 °C and allowed to react for 12 h. The MCM powder was collected by filtration and washed repeatedly with CH2CI2. After drying in vacuo at 50 °C, 1.3 g of 3-chloropropyl MCM 2 was obtained. Elemental analysis and weight gain showed that 3.0 mmol of 3-(chloropropyl) trimethoxysilane was immobilized on 1.0 g of MCM-41 silica 1. 2.3. Preparation of MCM-41-supported norephedrine 3. To a solution of (+)-norephedrine (0.68 mg , 4.5 mmol) and triethylamine (0.33 g, 3.3 mmol) in toluene (10 mL) was added 3-chloropropyl MCM 2 (1.0 g). The mixture was gradually heated to 110 °C and allowed to react for 48 h. The powder was collected by filtration and washed successively with H2O, ethanol, and CH2CI2. After drying in vacuo at 50 "C, 1.2 g of MCM-41-supported norephedrine 3 was obtained. Elemental analysis and weight gain showed that 1.83 mmol of norephedrine was anchored on 1.0 g of 3-chloropropyl MCM 2. 2.4. Typical procedure for the Ru-catalyzed asymmetric transfer hydrogenation using MCM-41 silica-supported norephedrine 3. A preparative experiment using 1.67 mmol of acetophenone (S/C=100) was performed as follows: A suspension formed by mixing [{RuCl2(p-cymene)}2] (5.1 mg 0.008 mmol) and MCM-41 silica-supported norephedrine 3 (10 mg, 0.07 mmol) in 2-propanol (5 mL) was heated at 80 °C for 30 min under an nitrogen atmosphere. To the resulting solution, a degassed solution of ketone (0.83 mmol) in 2-propanol (10 mL) and a solution of KOH (2.2 mg, 0.04 mmol) in propane-2-ol (1.0 ml) were added. The mixture was stirred at RT for 12-20 h, neutralized with dilute hydrochloric acid and concentrated in vacuo. The residue was diluted with ethyl acetate and the organic solution was washed with brine. The organic layer was dried over MgS04, concentrated under reduced pressure. The residue was purified by column chromatography (hexane-ethyl acetate,95:5, as eluent) and vacuum distillation to yield the pure alcohol. The enantiomeric excess was determined HPLC analysis using Chiralcel OB-H column (5% 2-propanol in hexane, 0.5ml/min).
3. RESULTS AND DISCUSSION The immobilization of norephedrine onto MCM-41 silica material was performed in two steps (Scheme 1). Reaction of MCM 1 with an excess of (3-chloropropyl) trimethoxysilane in refluxing toluene gave chloropropylsilanized MCM 2 (3.0 mequiv /g). Subsequent treatment of 2 with 1.5 equiv of (-i-)-norephedrine in refluxing toluene in the presence of 1.1 equiv of triethylamine afforded MCM-supported norephedrine 3 (1.83 mequiv/g). The MCMsupported chiral Ru(II) complexes were prepared in situ by heating a mixture of 3 and [Ru(arene)Cl2]2'^ in 2-propanol. Asymmetric transfer hydrogenation of several ketones with isopropanol as a hydrogen source was examined in the presence of the Ru(II) catalyst. As indicated in Table 1, all the ketones were reduced to (i?)-secondary alcohols with moderate to high enantioselectivities in reasonable conversions. The e.e. and conversion seem to depend on the structure of the substrate. The highest enantioselectivity was observed for the hydrogen transfer of atetralone. An even better e.e. can be obtained when the reaction is carried out in the presence of [Ru(HMB)Cl2]2". As the bulkiness of the alkyl substituent increases, the extend of e.e. (enantiomeric excess) is lowered. The conversion of the product decreases with increasing the e.e. It is noteworthy that the MCM-supported ligand 3 is as effective as comparable free (+)-ephedrine ligand in terms of enantioselectivity."^
511
Table 1. Asymmetric transfer hydrogenation of ketones in 2-propanol using MCM-supported ligand 3^
c/-
MCM-41-supported ligand 3 [Ru(arene)Cl2]2 /PrOH, KOH
OH
C
Entry
Substrate
Arene
Time (h)
Conv. (%)
% e.e."
1
R=Me
/?-cymene
12
96
81
2b
R=Me
/?-cymene
12
74
81
3
R=Et
/?-cymene
12
90
71
4^
R=Et
/?-cymene
15
70
70
5
R=Me
HMB'*
14
73
85
7
R=Et
HMB
16
60
78
8
a-tetralone
/?-cymene
18
70
80
9
a-tetralone
p-cymene
20
72
89
10
a-tetralone
HMB
16
50
95
"The reaction was carried out at RT using 0.1 M solution of ketone (5.0 mmol) in 2-propanol; ketone: Ru: ligand: KOH = 100: 1 : 1 : 5 . ^Ketone: Ru: ligand: KOH = 200: 1: 2: 5. "^Determined by HPLC analysis using Chiralcel OB-H column (5% 2-propanol in hexane, 0.5ml/min). ''HMB = hexamethylbenzene.
In conclusion, we have shown that the MCM-41 can be served as a potential support for the heterogeneous chiral ligand. Our studies strongly support the possibility of achieving high reactivity and enantioselectivity in heterogeneous systems. Further synthesis of MCMsupported chiral ligands and their use to asymmetric catalysis are underway in our laboratory. This work was supported by the Center for Advanced Bioseparation Technology, Inha University. REFERENCES 1. Zassinovich, G.; Mestronu, G.; Gladiali, S. Chem. Rev. 1992, 92, 1051. 2. Noyori, R.; Hashiguchi, S. Ace. Chem. Res., 1997, 30, 97.
512
3. Takehara, J.; Hashiguchi, S.; Fujii, A.; Inoue, S.-I.; Ikariya, T.; Noyori, R. J. Chem. Soc, Chem. Commun., 1996, 233. 4. Murata, K.; Ikariya, T. J. Org. Chem., 1999, 64, 2186. 5. Yamakawa, M.; Ito, H.; Noyori, R. J. Am. Chem. Joe, 2000, 122, 1466. 6. Alonso, D. A.; Guijarro, D.; Pinho, P.; Temme, O.; Andersson, P. G. . J. Org. Chem., 1998, 63, 2749. 7. Hodge, P and Sherrington, D. C. in Polymer-Supported Reactions in Organic Synthesis, Wiley, New York, 1980 8. Smith, K. Solid Supports and Catalysts in Organic Synthesis, Ellis Horwood and Prentice Hall, New York, 1992. 9. Liu, C.-H.; Yu, W.-Y. J. Org Chem., 1998, 63, 7364. 10. Bennete, M. A.; Smith, A. K. J. Chem. Soc, Dalton Trans., 1974, 233. 11. Bennete, M. A.; Matheson, T. W.; Robertson, G. B.; Smith, A. K.; Tucker, P. A. Inorg. Chem., 1980, 19, 1014 12. Ryoo, R.: Jun, S. J. Phys. Chem. B, 1997, 101, 317.
509
MCM-41-supported norephedrine ligand for ruthenium-catalyzed asymmetric transfer hydrogenation of ketones Myung-Jong Jin, Sang-Han Kim, Sang-Joon Lee, and Wha-Seung Ahn School of Chemical Science & Engineering, Inha University, Inchon, 402-751, Korea Optically active norephedrine was anchored on MCM-41 silica material. The insoluble system was utilized as an enantioselective ligand in the asymmetric transfer hydrogenation of ketones. This reaction provided (/?)-secondary alcohols with satisfactory enantioselectivities (up to 95% ee) in good conversion. The results are comparable to those of the analogous homogeneous counterpart. 1. INTRODUCTION Transition metal complex-catalyzed asymmetric transfer hydrogenation of ketones is an attractive method for the synthesis of optically active secondary alcohols.'"^ Efficient chiral ligands have been developed for the homogeneous catalysis. Successful development of homogeneous ligands has been sometimes followed by attempts to attach the ligands on an insoluble polymeric support. This strategy offers practical advantages such as simplified separation, easy recovery of catalyst, and potential reuse.^'^ Polystyrene resin, silica gel and alumina have been most commonly used as supports for the immobilization of the ligands. Recently, mesoporous molecular sieves MCM materials with large uniform pore diameters and high specific surface areas have become of high interest as inorganic supports.'^ Our interest in the field led to prepare a new MCM-41 silica-supported norephedrine ligand 3. Herein, we describe the application of the supported ligand for the asymmetric transfer hydrogenation of ketones. Scheme I Mq,
(—^" MCM-41 —OH 1
i •
|—^\ ^ w x r~^7^' C' 2
ii
?h
|^ 3
i) (McO)3Si(CH2)3Cl, toluene, reflux ii) (+)-norcphcdrinc - EtjN, toluene, reflux 2. EXPERIMENTAL 2.1. Preparation of MCM-41 silica 1. MCM-41 silica 1 was prepared according to the literature method using surfactant Ci6H33N(CH3)3Br as the template.'^ 2.2. Preparation of 3-chIoropropyl MCM 2. To a solution of 3-(chloropropyl)trimethoxysilane (0.72 g, 3.6 mmol) in toluene (10 mL)
510
was added MCM-41 silica (1.0 g). The mixture was gradually heated to 110 °C and allowed to react for 12 h. The MCM powder was collected by filtration and washed repeatedly with CH2CI2. After drying in vacuo at 50 °C, 1.3 g of 3-chloropropyl MCM 2 was obtained. Elemental analysis and weight gain showed that 3.0 mmol of 3-(chloropropyl) trimethoxysilane was immobilized on 1.0 g of MCM-41 silica 1. 2.3. Preparation of MCM-41-supported norephedrine 3. To a solution of (+)-norephedrine (0.68 mg , 4.5 mmol) and triethylamine (0.33 g, 3.3 mmol) in toluene (10 mL) was added 3-chloropropyl MCM 2 (1.0 g). The mixture was gradually heated to 110 °C and allowed to react for 48 h. The powder was collected by filtration and washed successively with H2O, ethanol, and CH2CI2. After drying in vacuo at 50 "C, 1.2 g of MCM-41-supported norephedrine 3 was obtained. Elemental analysis and weight gain showed that 1.83 mmol of norephedrine was anchored on 1.0 g of 3-chloropropyl MCM 2. 2.4. Typical procedure for the Ru-catalyzed asymmetric transfer hydrogenation using MCM-41 silica-supported norephedrine 3. A preparative experiment using 1.67 mmol of acetophenone (S/C=100) was performed as follows: A suspension formed by mixing [{RuCl2(p-cymene)}2] (5.1 mg 0.008 mmol) and MCM-41 silica-supported norephedrine 3 (10 mg, 0.07 mmol) in 2-propanol (5 mL) was heated at 80 °C for 30 min under an nitrogen atmosphere. To the resulting solution, a degassed solution of ketone (0.83 mmol) in 2-propanol (10 mL) and a solution of KOH (2.2 mg, 0.04 mmol) in propane-2-ol (1.0 ml) were added. The mixture was stirred at RT for 12-20 h, neutralized with dilute hydrochloric acid and concentrated in vacuo. The residue was diluted with ethyl acetate and the organic solution was washed with brine. The organic layer was dried over MgS04, concentrated under reduced pressure. The residue was purified by column chromatography (hexane-ethyl acetate,95:5, as eluent) and vacuum distillation to yield the pure alcohol. The enantiomeric excess was determined HPLC analysis using Chiralcel OB-H column (5% 2-propanol in hexane, 0.5ml/min).
3. RESULTS AND DISCUSSION The immobilization of norephedrine onto MCM-41 silica material was performed in two steps (Scheme 1). Reaction of MCM 1 with an excess of (3-chloropropyl) trimethoxysilane in refluxing toluene gave chloropropylsilanized MCM 2 (3.0 mequiv /g). Subsequent treatment of 2 with 1.5 equiv of (-i-)-norephedrine in refluxing toluene in the presence of 1.1 equiv of triethylamine afforded MCM-supported norephedrine 3 (1.83 mequiv/g). The MCMsupported chiral Ru(II) complexes were prepared in situ by heating a mixture of 3 and [Ru(arene)Cl2]2'^ in 2-propanol. Asymmetric transfer hydrogenation of several ketones with isopropanol as a hydrogen source was examined in the presence of the Ru(II) catalyst. As indicated in Table 1, all the ketones were reduced to (i?)-secondary alcohols with moderate to high enantioselectivities in reasonable conversions. The e.e. and conversion seem to depend on the structure of the substrate. The highest enantioselectivity was observed for the hydrogen transfer of atetralone. An even better e.e. can be obtained when the reaction is carried out in the presence of [Ru(HMB)Cl2]2". As the bulkiness of the alkyl substituent increases, the extend of e.e. (enantiomeric excess) is lowered. The conversion of the product decreases with increasing the e.e. It is noteworthy that the MCM-supported ligand 3 is as effective as comparable free (+)-ephedrine ligand in terms of enantioselectivity."^
511
Table 1. Asymmetric transfer hydrogenation of ketones in 2-propanol using MCM-supported ligand 3^
c/-
MCM-41-supported ligand 3 [Ru(arene)Cl2]2 /PrOH, KOH
OH
C
Entry
Substrate
Arene
Time (h)
Conv. (%)
% e.e."
1
R=Me
/?-cymene
12
96
81
2b
R=Me
/?-cymene
12
74
81
3
R=Et
/?-cymene
12
90
71
4^
R=Et
/?-cymene
15
70
70
5
R=Me
HMB'*
14
73
85
7
R=Et
HMB
16
60
78
8
a-tetralone
/?-cymene
18
70
80
9
a-tetralone
p-cymene
20
72
89
10
a-tetralone
HMB
16
50
95
"The reaction was carried out at RT using 0.1 M solution of ketone (5.0 mmol) in 2-propanol; ketone: Ru: ligand: KOH = 100: 1 : 1 : 5 . ^Ketone: Ru: ligand: KOH = 200: 1: 2: 5. "^Determined by HPLC analysis using Chiralcel OB-H column (5% 2-propanol in hexane, 0.5ml/min). ''HMB = hexamethylbenzene.
In conclusion, we have shown that the MCM-41 can be served as a potential support for the heterogeneous chiral ligand. Our studies strongly support the possibility of achieving high reactivity and enantioselectivity in heterogeneous systems. Further synthesis of MCMsupported chiral ligands and their use to asymmetric catalysis are underway in our laboratory. This work was supported by the Center for Advanced Bioseparation Technology, Inha University. REFERENCES 1. Zassinovich, G.; Mestronu, G.; Gladiali, S. Chem. Rev. 1992, 92, 1051. 2. Noyori, R.; Hashiguchi, S. Ace. Chem. Res., 1997, 30, 97.
512
3. Takehara, J.; Hashiguchi, S.; Fujii, A.; Inoue, S.-I.; Ikariya, T.; Noyori, R. J. Chem. Soc, Chem. Commun., 1996, 233. 4. Murata, K.; Ikariya, T. J. Org. Chem., 1999, 64, 2186. 5. Yamakawa, M.; Ito, H.; Noyori, R. J. Am. Chem. Joe, 2000, 122, 1466. 6. Alonso, D. A.; Guijarro, D.; Pinho, P.; Temme, O.; Andersson, P. G. . J. Org. Chem., 1998, 63, 2749. 7. Hodge, P and Sherrington, D. C. in Polymer-Supported Reactions in Organic Synthesis, Wiley, New York, 1980 8. Smith, K. Solid Supports and Catalysts in Organic Synthesis, Ellis Horwood and Prentice Hall, New York, 1992. 9. Liu, C.-H.; Yu, W.-Y. J. Org Chem., 1998, 63, 7364. 10. Bennete, M. A.; Smith, A. K. J. Chem. Soc, Dalton Trans., 1974, 233. 11. Bennete, M. A.; Matheson, T. W.; Robertson, G. B.; Smith, A. K.; Tucker, P. A. Inorg. Chem., 1980, 19, 1014 12. Ryoo, R.: Jun, S. J. Phys. Chem. B, 1997, 101, 317.