不对称催化氢化Word文件下载.docx

1、催化氢化都是膦配体。有如下三种途径合成手性膦配体。手性中心在膦上，P-手性配体；手性中心在碳上，C-手性配体；既有膦又有碳手性中心的配体。常见的手性膦配体单齿配体 PAMP CAMP MonoPhos双齿配体 DEGPHOS DuPHOS PNNP RROPHOS NORPHOS BPPFA CYCPHOS （R,R）-DIPAMP （S,S）-CHIRAPHOS （R）-BINAP （S,S）-BPPM DIOP（R,R）-DPCP （+）-DIPMC （2R,3R）-NORPHOS （-）-MENO BIPHEMP SpirOP BICP中心金属主要限于铑（Rh）和钌（Ru）两种贵金属，另

2、外铱（Ir）有少量的应用。手性铑（Rh）膦催化剂只对酰氨基丙烯酸衍生物的催化氢化有很好的结果，对其它底物对映体选择性很低。手性钌（Ru）膦催化剂底物适用范围广，尤其是Noyori等发展的Ru（BINAP）（OCOR）2催化剂能用于C=C,C=O, C=N等的不对称氢化，得到特别优异的对映体选择性。2.1.3 不对称催化机理手性铑（Rh）膦催化剂对酰氨基丙烯酸衍生物的氢化催化结果如下：Phosphine Ligand% e.e. of the productR = C6H5R = H（R,R）-DIPAMP96（S）94（S）（S,S）-CHIRAPHOS99（R）91（R）（S,S）-NORP

3、HOS95（S）90（R）（R,R）-DIOP85（R）73（R）（S）-BINAP98.5（R）a（S,S）-BPPM100（R）a98（R）（S）-BPPFA93（S）（S,S）-SKEWPHOS92（R）（S,S）-CYCPHOS88（R）（S,S）-Et-DuPHOS99（S）a. hydrogenateon of N-benzoyl derivativeHalpern等人以及Brown等人对手性铑（Rh）膦催化剂的机理进行了详尽的研究。烯烃能用Re面或者Si面与手性催化剂配位生成两个非对映体，氧化加成（K2）是速率控制步骤。手性钌（Ru）膦催化剂催化机理Ru（II）的配位数比Rh（I

4、）大，可形成六配位数的八面体结构，后者只形成四面体结构。机理更加复杂，形成单氢形式的活性中间体。Halpern提出了机理如下Organic Syntheses, CV 9, 169ASYMMETRIC HYDROGENATION OF ALLYLIC ALCOHOLS USING BINAP-RUTHENIUM COMPLEXES: （S）-（）-CITRONELLOL6-Octen-1-ol, 3,7-dimethyl, （S）-Submitted by Hidemasa Takaya1, Tetsuo Ohta1, Shin-ichi Inoue2, Makoto Tokunaga2, M

5、asato Kitamura2, and Ryoji Noyori2.Checked by Andrew Madin and Larry E. Overman.1. ProcedureCaution! BINAP-Ru complexes are rapidly oxidized in solution in the presence of air, and all procedures should be carried out under anaerobic conditions using degassed solvents.A. （R）-2,2-Bis（diphenylphosphin

6、o）-1,1-binaphthylruthenium diacetate, Ru（OCOCH3）2（R）-BINAP. A dry, 150-mL Schlenk tube （Note 1） connected to a supply of argon （Note 2） is equipped with a Teflon-coated magnetic stirring bar and a glass stopper. The vessel is charged with benzeneruthenium（II） chloride dimer, RuCl2（benzene）2, （800 mg

7、, 1.60 mmol） （Note 3） and （R）-BINAP （1.89 g, 3.04 mmol） （Note 4）, evacuated, and then filled with argon. N,N-Dimethylformamide （DMF） （30 mL） （Note 5） is introduced with a hypodermic syringe under the stream of argon. The reddish brown suspension is stirred at 100C for 10 min （Note 6） and the resulti

8、ng clear reddish brown solution （Note 7） is cooled. Another dry, 60-mL Schlenk tube is charged with sodium acetate （5.20 g, 63.4 mmol） and methanol （50 mL） （Note 8） and the solution is degassed by three freeze-thaw cycles. It is transferred into the DMF solution of BINAP-Ru（II） complex prepared abov

9、e via cannula and the solution is stirred at 25C for 5 min. To the solution are added water （50 mL） and toluene （25 mL） under argon and the resulting two layers are mixed by vigorous stirring. The upper organic layer is transferred into another 200-mL Schlenk tube （Note 9） using a cannula. The aqueo

10、us layer is vigorously mixed with toluene （25 mL） and the upper organic layer is again transferred into the Schlenk tube. This procedure is repeated once more. The combined organic layers are washed with four 10-mL portions of water （Note 10）. Removal of the solvent at 1 mm and 40C for 30 min with v

11、igorous stirring （Note 11） and evacuation at 0.1 mm and 25C for 12 hr gives 2.542.67 g of solid Ru（OCOCH3）2 （R）-BINAP （99104% crude yield based on BINAP） （Note 12）. It is dissolved in toluene （2025 mL） with heating. Hexane （80100 mL） is added very carefully to the solution down the side of the flask

12、 to form two layers. The solution is left at 25C for 12 hr and then at 4C for 3 days to give solid material. Removal of the mother liquor is followed by washing with hexane （20 mL） and drying under reduced pressure to afford 1.82.2 g （7185% yield） of pure Ru（OCOCH3）2 （R）-BINAP as fine yellow needles

13、 or powdery crystals; mp 188190C dec （Note 13）.B. （S）-（）-Citronellol. Geraniol （12.9 mL, 74 mmol） （Note 14） and 95% methanol （15 mL） （Note 15） are placed in a dry, 80-mL Schlenk tube and the mixture is degassed by five freeze-thaw cycles. Another dry, 80-mL Schlenk tube, equipped with a rubber septu

14、m and a magnetic stirring bar and filled with argon, is charged with Ru（OCOCH3）2 （R）-BINAP （45 mg, 53 mol） （Note 16）. The system is evacuated and refilled with argon three times. By use of a cannula, the solution of geraniol in methanol is introduced into the Schlenk tube containing the ruthenium co

15、mplex under argon. The resulting light yellow solution （Note 17） is then transferred with a cannula into a 100-mL, stainless steel autoclave equipped with a glass vessel （Note 18） and a magnetic stirring bar by use of a slight positive pressure of argon. The autoclave is connected to a hydrogen sour

16、ce （Note 19） using the arrangement shown in Figure 1, and the air originally present in the gas-inlet tube is replaced by hydrogen （Note 20）. Valve A is opened and hydrogen is introduced until pressure gauge B indicates 100 atm. The solution is stirred at 20C for 816 hr （Note 21）. During hydrogenati

17、on, the hydrogen pressure is kept above 90 atm by the occasional introduction of hydrogen from the cylinder （Note 22）. When consumption of hydrogen ceases, the gas-inlet tube is disconnected. Excess hydrogen is carefully released by opening valve A and then the apparatus is disassembled. The yellowi

18、sh brown contents （Note 23） are transferred to a 50-mL flask and the solvent is removed by a rotary evaporator. The residue （Note 24） is distilled under reduced pressure to give 10.711.2 g （9397% yield） of （S）-（）-citronellol in 98% ee （Note 25） and （Note 26）; bp 5862C/0.01 mm.Figure 12. Notes1. Befo

19、re use, all apparatus is dried overnight in a 120C oven.2. Argon （99.998%） is purified by passing through a BASF catalyst RC-11 column at 80C and then through 4 molecular sieves.3. RuCl2（benzene）2, available from Aldrich Chemical Company, Inc., is used without purification.4. BINAP 2,2-bis（diphenylp

20、hosphino）-1,1-binaphthyl is commercially available or can be prepared according to a literature procedure.3 The diphosphine is slowly oxidized in air to give the corresponding mono- and diphosphine oxides that can be removed by column chromatography （silica gel, benzene） under an inert atmosphere.5.

21、 Guaranteed grade DMF, available from NACALAI TESQUE, Inc., is distilled over 4 molecular sieves under argon before use and stored in a 100-mL Schlenk tube. It is degassed by three freeze-thaw cycles.6. Reaction at a higher temperature for a longer period leads to formation of the ruthenium carbonyl

22、 complex IR（KBr） 1964 cm1.7. The solution may be a crude mixture of cationic BINAP-Ru（II） complexes such as RuCl（BINAP）（DMF）3Cl and Ru（BINAP）（DMF）4Cl2. Physical properties include conductivity, 27 Scm2/mol （DMF）; 31P NMR （4:1 DMF-CDCl3） : 60.6 （d, J = 46）, 61.4 （d, J = 46）, 61.8 （s）. The （R）-BINAP-R

23、u（II） complex obtained by removal of the solvent can catalyze hydrogenation of geraniol （98.7% pure commercial geraniol containing 1.3% of nerol, distilled from 4 molecular sieves）. However, in addition to （S）-citronellol in 9596% ee, dihydrocitronellol, an overreduction product, is obtained in 37%

24、yield （1.1 M substrate in 95% aqueous methanol, 1.7 mM catalyst, 100 atm of H2, 20C, 8 hr）.8. Guaranteed grade methanol is distilled under argon.9. The diameter is about 4 cm.10. The extraction procedure must be carried out under an argon atmosphere.11. Under reduced pressure, the solution sometimes

25、 foams. This can be avoided by heating the top part of the Schlenk tube with a hot air gun.12. Crude BINAP-Ru complex with consistent spectral characteristics can be used for hydrogenation of geraniol （98.7% pure commercial geraniol containing 1.3% of nerol, distilled from 4 molecular sieves, 4.7 M

26、substrate in 95% aqueous methanol, 2.8 mM Ru（OCOCH3）2 （R）-BINAP, 100 atm of H2, 20C, 8 hr）, to give （S）-citronellol in 96% ee, 97% isolated yield.13. The product has the following spectral properties: 1H NMR （CDCl3） : 1.80 （s, 2 OCOCH3）, 6.477.84 （m, aromatic protons）; 31P NMR （CDCl3） : 65.13 （s）; 1

27、3C NMR （CDCl3） :23.50, 125.2138.3, 188.1; IR （CH2Cl2） cm1: 1452, 1518. An analytical sample is prepared by drying at 110C and 0.01 mm for 12 hr: Calcd for C48H38O4P2Ru: C, 68.5; H, 4.6. Found: C, 68.4; H, 4.5.14. Pure geraniol is obtained by fractional distillation using a 1000 theoretical plate col

28、umn. The checkers obtained geraniol, 99.5% purity by GC analysis, from Fluka Chemical Company and used it directly.15. The 95% methanol is prepared by mixing distilled, guaranteed methanol （95 mL） and water （5 mL）. If absolute methanol or 90% aqueous methanol is used as solvent, somewhat longer reac

29、tion times are needed.16. The complex can be stored under argon without noticeable loss of catalytic activity. It is weighed under an argon atmosphere.17. The ruthenium complex is moderately soluble in methanol. Ultrasonic stirring is employed for complete solution.18. A glass vessel is used for kee

30、ping the reaction mixture away from the stainless steel wall. The reaction system is evacuated and filled with argon three times before use.19. The purity of hydrogen （Nippon Sanso Co.） used by the submitters is 99.99999%. The checkers used hydrogen of 99.99% purity.20. The gas-inlet tube is attached to the autoclave and then the main valve of the cylinder is opened. After closing the main valve of the cylinder, the connector of the gas-inlet tube is loosened to release hydrogen pressure and tightened immediately. This procedure is repeated five times.21. To