不对称二羟基化反应中可循环使用的催化体系研究
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摘要
手性锇催化剂催化的烯烃不对称二羟基化反应(简称AD反应)是合成手性邻二醇最有效的途径之一，可以将几乎所有类型的烯烃转变成相应的手性邻二醇，因此广泛地应用于药物、天然产物以及精细化工产品的合成。AD反应中使用的催化剂是由手性配体及OsO_4原位产生的，但由于手性配体和OsO_4非常昂贵，加之OsO_4毒性大，极易挥发，限制了AD反应的工业化应用，因此，开发可回收和重复使用的手性锇催化剂是目前亟待解决的重大课题。目前的研究主要集中在两个方面：一方面，将手性配体共价键合到不溶或可溶性载体上制成负载手性配体，但在重复使用负载配体时必须补充OsO_4，才能保证催化活性不降低；另一方面，将OsO_4包裹在高聚物微囊内，或运用离子交换技术或共价键合的方法将OsO_4固载在树脂、硅胶或层状双金属氢氧化物材料上，但手性配体却不能同时回收。目前，关于AD反应中手性配体和OsO_4同时定量回收和重复使用问题已成为国外多个研究小组关注的热点。最近，聚乙二醇(PEG，FW 400)及离子液体被用于AD反应中OsO_4及手性配体的同时回收，但是仍然存在手性配体或OsO_4的流失，以及二者用量大等不足，因此，
第四军医大学博士学位论文
该方法并没有有效地解决两种催化组份同时回收的问题。
本论文的研究方向是AD反应中手性配体和手性催化剂的回
收和重复使用，研究工作包括以下七个方面:
1.根据金鸡纳生物碱衍生物配体的构效关系，设计并合成了三
种手性双金鸡纳生物碱单季钱盐配体8、9和10。
以奎宁和奎尼定为原料分别与1，4一二氯一2，3一二氮杂蔡反应制
备(QN)ZPHAL和(Qn)ZPHAL，然后通过(QN)ZPHAL、(oHQ)2-
PHAL及(QD)ZPHAL与节基滇的季按化反应制备单季钱盐手性配
体8、9和10。
2.分别以PEG或离子液体【bmim』PF6作为反应介质，NMO为共氧
化剂，将配体与四氧化饿原位配位用于烯烃的AD反应，反应结
束后只需用甲基叔丁基醚萃取即可得产物，配体与四氧化饿则由
于在甲基叔丁基醚中不溶解以及PEG或离子液体对0504的包裹
作用而留在反应介质中继续循环使用。催化结果如下:
(l)在PEG/NMO体系中，将配体8用于八种烯烃的AD反应，
配体、0504和底物的摩尔比为0.02/0.005/l时，化学产率为
78一90%，除反式一5一癸烯和蔡基烯丙基醚较低外，其它六种烯烃
的相应二醇产物的ee值为78一96%。在该催化体系中，降低温度有
利于提高立体选择性。以反式二苯乙烯为底物，在PEG/NMO体
系中进行的AD反应，手性配体8和0504可连续回收和重复使用5
次，仍保持较高的催化活性及立体选择性。
(2)配体9与配体8在结构上的差别是奎宁环上连的不是两个乙
烯基而是两个乙基，因此9在AD反应中不会被氧化。在与8相同
的催化反应条件下，手性配体9催化八种烯烃的AD反应得到的化
学产率和ee值分别为70一90%和77一96%(反式一5一癸烯和蔡基烯丙
基醚除外)。在反式二苯乙烯的AD反应中，手性配体9和0504可
连续回收和重复使用5次，仍然保持较高的催化活性及立体选择
性。实验结果表明将双金鸡纳生物碱衍生物配体分子中一个奎宁
环上的N原子季钱化可以保证单季按盐配体的回收。
(3)配体10和配体8是一对假对映异构体，在AD反应中立体选
第四军医大学博士学位论文
择面相反，可得到相反构型的产物。在与8相同的催化反应条件
下，手性配体10催化八种烯烃的AD反应得到的化学产率和ee值
分别为72一90%和79~96%(反式一5一癸烯和蔡基烯丙基醚除外)。在
反式二苯乙烯的AD反应中，手性配体10和0504可连续回收和重
复使用5次，仍然保持较高的催化活性及立体选择性。
(4)在[bmim]PF6/NMO体系中，将配体8和10分别用于八种烯
烃的AD反应，配体、0504和底物的摩尔t匕为0.02/0.015/l时，化
学产率分别为67一91%和61一90%，ee值分别为66一99.9%和
68一99.9%(反式一5一癸烯和蔡基烯丙基醚除外)。在反式二苯乙烯
的AD反应中，手性配体和0504可连续回收和重复使用5次，仍然
保持较高的催化活性及立体选择性。
在PEG/NMO及[bmim]PF6/NMO体系中，配体8，9和10对反
式二取代烯烃的对映选择性( 94~99.9%ee)明显优于对链端烯烃的
对映选择性(66一81%ee)。对芳香族烯烃的立体选择性高于脂肪族
烯烃，与商品配体(DHQ)ZPHAL及(DHQD)ZPHAL的催化特性相
似。与目前的文献报道相比，我们的催化体系具有以下特点:①
两种催化组分可同时回收，在重复使用的过程中，无需补加配体
和0504;②配体及0504的使用量少;③适用底物的范围广。该
催化体系优于目前国内外相关研究报道的催化体系。
3.用离子液体[e mim】BF4代替[b mim」PF6作为反应介质进行AD反
应，实验结果显示0504和手性配体严重流失，表明【emim」BF4
和【bmim』PF6虽然都是1，3一二烷基咪哇盐类离子液体，但他们在阳
离子和阴离子结构上的差别对催化剂的回收有较大的影响。
4.为了提高050;的回收率，我们制备了一种可回收和重复使用
的TentaGel支载050;催化剂。该催化剂集中了均相和多相催化
剂的优点:除具有一般树脂优秀的溶胀性能、易分离及可循环使
用等特点外，最为重要的是它特有的聚乙二醇长链，既有水溶性，
使连接在链端的手性配体?
The osmium-catalyzed asymmetric dihydroxylation (AD) of olefins provides one of the most effective methods for the preparation of vicinal diols. Almost all kinds of olefmic substrates can be transformed to the corresponding diols by means of AD reaction. The chiral osmium catalyst is generated in situ by the chiral ligand complexing with Os04 in the reaction. Although AD reaction can be widely applied to the synthesis of Pharmaceuticals, natural products and fine chemicals, the high cost of osmium and chiral ligands as well as the high toxicity and volatility of the osmium component has restricted its use in industry. So exploration of the repetitive use of the chiral osmium catalyst for AD reaction is urgent. The present research work focuses on two aspects. On one hand, the most successful alkaloid-derived ligands have been attached to a soluble or insoluble support covalently, but additional OsO4 is necessary to maintain the consistent catalytic activity during the reuse of supported chiral ligand in the
next AD reaction. On the other hand, immobilization of osmium tetroxide based on microencapsulation, ion-exchange techniques, and osmylation of resins has made it possible to recover and reuse of the osmium, but failed to recover the
chiral ligand at the same time. At present, simultaneous recovery and reuse of the chiral ligand and OsO4 are of major interest. Very recently, an ionic liquid and (ethylene glycol) (PEG, FW 400) have been employed as reaction media as well as immobilizing agents for the catalyst in AD reaction. However, the high molar ratio of the OsO4/ligand/substrate (0.01/0.05/1) and obvious leaching of both catalytic components made these attempts ineffective.
The research work of this thesis focuses on the development of the recoverable and reusable chiral catalysts and catalytic system in the AD reaction of olefins. It mainly includes following aspects:
1. Three chiral mono-quaterized bis-cinchona alkaloid ligands 8, 9, 10 were designed and synthesized.
Treatment of 1,4-dichlorophthalazine with quinine or quinidine provided (QN)2PHAL and (QD)2PHAL. (QN)2PHAL, (DHQ)2PHAL and (QD)2PHAL were quaternized by refluxing with benzyl bromide to give ligands 8, 9 and 10 respectively.
2. The chiral ligands were applied to the AD reaction of olefins with NMO as co-oxidant and PEG (400 MW) or [bmimjPFs as reaction media. When the reaction was finished, the product diol could be extracted by tert-butyl methyl ether, while most of the alkaloid ligand and osmium tetroxide were remained in the reaction media due to the low solubility of the ligand in ether and special encapsulating effect of ionic liquid and PEG on osmium tetroxide. The recovered ionic liquid or PEG phase containing ligand and OsO4 could be recycled five times without any addition of OsO4 and ligand. The results of AD reactions are as follows:
(1) When the AD reaction of eight olefins was performed at 0.5mol% Os04 and 2mol% ligand 8 in PEG/ NMO system, the diols were obtained in 78-90% yields and 78-96% ees (except for frww-5-decene and ally naphthyl ether). We also found that low temperature (0 C) was benefit to increasing entioselectivity. In the recycling experiments of AD reaction, with trans-stilbene being substrate, chiral ligand 8 and OsO4 could be recovered
and reused for five times with high catalytic activity and stereoselectivity.
(2) The ligand 9 is different from ligand 8 in that the substitute group at the 3-position of quinuclidine is ethyl group, so it won't be oxidized in the AD reaction. 9 was applied to the AD reaction of eight olefins in PEG/ NMO system according to the protocol of ligand 8. The yields and ees of the diols were 70-90% and 77~96%( except for trans-5-decenc and ally naphthyl ether) respectively. With trans-stilbene as the substrate, chiral ligand and OsO4 could be recovered and reused five times in the AD reaction with high catalytic activity and stereoselectivity.
(3) ligand 10 and 8 are pseudo-enantiomers, and the AD reactions using ligand 8 and 10 delivered chiral diols of opposite configurat
第四军医大学博士学位论文
该方法并没有有效地解决两种催化组份同时回收的问题。
本论文的研究方向是AD反应中手性配体和手性催化剂的回
收和重复使用，研究工作包括以下七个方面:
1.根据金鸡纳生物碱衍生物配体的构效关系，设计并合成了三
种手性双金鸡纳生物碱单季钱盐配体8、9和10。
以奎宁和奎尼定为原料分别与1，4一二氯一2，3一二氮杂蔡反应制
备(QN)ZPHAL和(Qn)ZPHAL，然后通过(QN)ZPHAL、(oHQ)2-
PHAL及(QD)ZPHAL与节基滇的季按化反应制备单季钱盐手性配
体8、9和10。
2.分别以PEG或离子液体【bmim』PF6作为反应介质，NMO为共氧
化剂，将配体与四氧化饿原位配位用于烯烃的AD反应，反应结
束后只需用甲基叔丁基醚萃取即可得产物，配体与四氧化饿则由
于在甲基叔丁基醚中不溶解以及PEG或离子液体对0504的包裹
作用而留在反应介质中继续循环使用。催化结果如下:
(l)在PEG/NMO体系中，将配体8用于八种烯烃的AD反应，
配体、0504和底物的摩尔比为0.02/0.005/l时，化学产率为
78一90%，除反式一5一癸烯和蔡基烯丙基醚较低外，其它六种烯烃
的相应二醇产物的ee值为78一96%。在该催化体系中，降低温度有
利于提高立体选择性。以反式二苯乙烯为底物，在PEG/NMO体
系中进行的AD反应，手性配体8和0504可连续回收和重复使用5
次，仍保持较高的催化活性及立体选择性。
(2)配体9与配体8在结构上的差别是奎宁环上连的不是两个乙
烯基而是两个乙基，因此9在AD反应中不会被氧化。在与8相同
的催化反应条件下，手性配体9催化八种烯烃的AD反应得到的化
学产率和ee值分别为70一90%和77一96%(反式一5一癸烯和蔡基烯丙
基醚除外)。在反式二苯乙烯的AD反应中，手性配体9和0504可
连续回收和重复使用5次，仍然保持较高的催化活性及立体选择
性。实验结果表明将双金鸡纳生物碱衍生物配体分子中一个奎宁
环上的N原子季钱化可以保证单季按盐配体的回收。
(3)配体10和配体8是一对假对映异构体，在AD反应中立体选
第四军医大学博士学位论文
择面相反，可得到相反构型的产物。在与8相同的催化反应条件
下，手性配体10催化八种烯烃的AD反应得到的化学产率和ee值
分别为72一90%和79~96%(反式一5一癸烯和蔡基烯丙基醚除外)。在
反式二苯乙烯的AD反应中，手性配体10和0504可连续回收和重
复使用5次，仍然保持较高的催化活性及立体选择性。
(4)在[bmim]PF6/NMO体系中，将配体8和10分别用于八种烯
烃的AD反应，配体、0504和底物的摩尔t匕为0.02/0.015/l时，化
学产率分别为67一91%和61一90%，ee值分别为66一99.9%和
68一99.9%(反式一5一癸烯和蔡基烯丙基醚除外)。在反式二苯乙烯
的AD反应中，手性配体和0504可连续回收和重复使用5次，仍然
保持较高的催化活性及立体选择性。
在PEG/NMO及[bmim]PF6/NMO体系中，配体8，9和10对反
式二取代烯烃的对映选择性( 94~99.9%ee)明显优于对链端烯烃的
对映选择性(66一81%ee)。对芳香族烯烃的立体选择性高于脂肪族
烯烃，与商品配体(DHQ)ZPHAL及(DHQD)ZPHAL的催化特性相
似。与目前的文献报道相比，我们的催化体系具有以下特点:①
两种催化组分可同时回收，在重复使用的过程中，无需补加配体
和0504;②配体及0504的使用量少;③适用底物的范围广。该
催化体系优于目前国内外相关研究报道的催化体系。
3.用离子液体[e mim】BF4代替[b mim」PF6作为反应介质进行AD反
应，实验结果显示0504和手性配体严重流失，表明【emim」BF4
和【bmim』PF6虽然都是1，3一二烷基咪哇盐类离子液体，但他们在阳
离子和阴离子结构上的差别对催化剂的回收有较大的影响。
4.为了提高050;的回收率，我们制备了一种可回收和重复使用
的TentaGel支载050;催化剂。该催化剂集中了均相和多相催化
剂的优点:除具有一般树脂优秀的溶胀性能、易分离及可循环使
用等特点外，最为重要的是它特有的聚乙二醇长链，既有水溶性，
使连接在链端的手性配体?
The osmium-catalyzed asymmetric dihydroxylation (AD) of olefins provides one of the most effective methods for the preparation of vicinal diols. Almost all kinds of olefmic substrates can be transformed to the corresponding diols by means of AD reaction. The chiral osmium catalyst is generated in situ by the chiral ligand complexing with Os04 in the reaction. Although AD reaction can be widely applied to the synthesis of Pharmaceuticals, natural products and fine chemicals, the high cost of osmium and chiral ligands as well as the high toxicity and volatility of the osmium component has restricted its use in industry. So exploration of the repetitive use of the chiral osmium catalyst for AD reaction is urgent. The present research work focuses on two aspects. On one hand, the most successful alkaloid-derived ligands have been attached to a soluble or insoluble support covalently, but additional OsO4 is necessary to maintain the consistent catalytic activity during the reuse of supported chiral ligand in the
next AD reaction. On the other hand, immobilization of osmium tetroxide based on microencapsulation, ion-exchange techniques, and osmylation of resins has made it possible to recover and reuse of the osmium, but failed to recover the
chiral ligand at the same time. At present, simultaneous recovery and reuse of the chiral ligand and OsO4 are of major interest. Very recently, an ionic liquid and (ethylene glycol) (PEG, FW 400) have been employed as reaction media as well as immobilizing agents for the catalyst in AD reaction. However, the high molar ratio of the OsO4/ligand/substrate (0.01/0.05/1) and obvious leaching of both catalytic components made these attempts ineffective.
The research work of this thesis focuses on the development of the recoverable and reusable chiral catalysts and catalytic system in the AD reaction of olefins. It mainly includes following aspects:
1. Three chiral mono-quaterized bis-cinchona alkaloid ligands 8, 9, 10 were designed and synthesized.
Treatment of 1,4-dichlorophthalazine with quinine or quinidine provided (QN)2PHAL and (QD)2PHAL. (QN)2PHAL, (DHQ)2PHAL and (QD)2PHAL were quaternized by refluxing with benzyl bromide to give ligands 8, 9 and 10 respectively.
2. The chiral ligands were applied to the AD reaction of olefins with NMO as co-oxidant and PEG (400 MW) or [bmimjPFs as reaction media. When the reaction was finished, the product diol could be extracted by tert-butyl methyl ether, while most of the alkaloid ligand and osmium tetroxide were remained in the reaction media due to the low solubility of the ligand in ether and special encapsulating effect of ionic liquid and PEG on osmium tetroxide. The recovered ionic liquid or PEG phase containing ligand and OsO4 could be recycled five times without any addition of OsO4 and ligand. The results of AD reactions are as follows:
(1) When the AD reaction of eight olefins was performed at 0.5mol% Os04 and 2mol% ligand 8 in PEG/ NMO system, the diols were obtained in 78-90% yields and 78-96% ees (except for frww-5-decene and ally naphthyl ether). We also found that low temperature (0 C) was benefit to increasing entioselectivity. In the recycling experiments of AD reaction, with trans-stilbene being substrate, chiral ligand 8 and OsO4 could be recovered
and reused for five times with high catalytic activity and stereoselectivity.
(2) The ligand 9 is different from ligand 8 in that the substitute group at the 3-position of quinuclidine is ethyl group, so it won't be oxidized in the AD reaction. 9 was applied to the AD reaction of eight olefins in PEG/ NMO system according to the protocol of ligand 8. The yields and ees of the diols were 70-90% and 77~96%( except for trans-5-decenc and ally naphthyl ether) respectively. With trans-stilbene as the substrate, chiral ligand and OsO4 could be recovered and reused five times in the AD reaction with high catalytic activity and stereoselectivity.
(3) ligand 10 and 8 are pseudo-enantiomers, and the AD reactions using ligand 8 and 10 delivered chiral diols of opposite configurat
引文
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[19] Pini. D.; Petri, A.; Rapaccini, P.; Salvadori, P. Chirality,1995,7:580.
[20] Pini, D.; Petri, A.; Salvad ori, P. Heterogeneous enantioselective dihydroxylation of aliphatic olefins: A comparison between different polymeric cinchona alkaloid derivatives, Tetrahedron Left, 1995, 36(9): 1549-1552.
[21] Salvadori, P.; Pini, D.; Petri, A. In defense of the catalytic dsymmetric cis dihydroxylation of olefins utilizing insoluble polymeric ligands. J Am Chem Soc, 1997, 119 (29): 6929-6930.
[22] Lohray, B. B.; Thomas, A.; chittari, P.; Ahuja, J. R.; Dhal, P. K. Asymmetric dihydroxylation of alkenes on polymer support: Scope and limitation, Tetrahedron Left, 1992, 33 (37) : 5453-5456.
[23] Song, C. E.; Yang, J. W.; Sa, H. J.; Lee, S. Efficient and practical polymeric catalysts for heterogeneous asymmetric dihydroxylation of olefins, Tetrahedron
Asymmetry, 1996, 7(3): 645-648.
[24] Canali, L.; Song, C. E.; Sherrington, D. C. Polymer-supported bis-cinchona alkaloid ligands for asymmetric dihydroxylation of alkenes a cautionary tale, Tetrahedron: Asymmetry. 1998, 9:1029-1034.
[25] Lohray, B.B.; Nandanan, E; Bhushan, V. catalytic asymmetric dihydroxylation of alkenes using silicagel supported cinchona alkaloid. Tetrahedron Asymmetry, 1996, 7(10): 2805-2808.
[26] Song, C. E.; Yong, J. W.; Sa, H. J. Silicagel supported bis-cinchona alkaloid: a highly efficient chiral ligand for heterogeneous asymmetric dihydroxylation of olefins. Tetrahedron Asymmetry, 1997, 8 (6):841-844.
[27] Bolm, C.; Maischak.A.; Gerlach, A. Asymmetric dihydroxylation with silica-ancho-red alkaloids. Chem Commun, 1997, 24: 2353-2354.
[28] Lee, H.M., Kim, S. W.; Hyeon, T.;Kim, B. M. Asymmetric dihydroxylation using heterogenized cinchona alkaloid ligands on mesoporous Silica, Tetrahedron Asymmetry, 2001, 12: 1537-1541.
[29] Motorina, I.;Crudden, C.M. Asymmetric dihydroxylation ofolefins using cinchona alkaloids on highly ordered inorganic supports. Organic Lett, 2001, 3 (15):2325-2328.
[30] Han, H; Janda, K.D. Soluble polymer-Bound ligand-accelerated catalysis: asymm etric dihydroxylation. J Am Chem Soc, 1996, 118 (32): 7632-7633.
[31] Han, H.; Janda, K.D. A soluble polymer-bound approach to the sharpless catalytic asymmetric dihydroxylation (AD) reaction: preparation and application of a [(DHQD)_2-PHAL-PEG-OMe] ligand. Tetrahedron Lett, 1997, 38 (9): 1527-1530.
[32] Bolm, C.; Gerlach, A. Angew Chem Int Ed Engl. 1997, 36:1731.
[33] Bolm, C.; Maischak, A. Synlett, 2001,93.
[34] Bolm, C.; Marischak, A.; Gerlach, A. Asymmetric dihydroxylation with silica-anchored alkaloids. Chem Commun, 1997, 2353-2354.
[35] Kuang, Y. Q.; Zhang, S.Y.; Wei, L.L. A simple and effective soluble polymer-bou- nd ligand for the asymmetric dihydroxylation of olefins: DHQD-PHAL-OPEG-OMe. Tetrahedron Lett, 2001, 42 (34) :5925-5927.
[36] Kuang, Y. Q.; Zhang, S. Y.; Wei, L.L. A soluble block copolymer-supported bis-cinchona alkaloid ligand for the asymmetric dihydroxylation of olefins. Synth Commun, 2003, 33 (20):3543-3548.
[37] Kuang, Y. Q.; Zhang, S.Y.; Jiang, R.; Wei, L.L. A free ligand for the asymmetric dihydroxylation of olefins utilizing one-phase catalysis and two-phase separation. Tetrahedron Lett, 2002, 42 (20) : 3669-3671.
[38] Kobayshi, S.; Endo, M.; Nagayma, S. Catalytic asymmetric dihydroxylation of olefins using a recoverable and reusable polymer-supported osmium catalyst. J Am Chem Soc, 1999, 121: 11229-11230.
[39] Kobayashi, S.; Ishida, T.; Akiyama, R. Catalytic asymmetric dihydroxylation using phenoxy-ethoxymethyl-polystyrene (PEM)-based novel microencapsulated osmium tetroxide (PEM-Mc OsO_4).Org Lett, 2000, 3 (17) : 2649-2652.
[40] Ishida, T.; Akiyama, R.; Kobayash, S. Microencapsulated osmium tetroxide-cataly-zed asymmetric dihydroxylation of olefins in water without organic cosolvents. Adv Synth catal, 2003, 345: 576-579.
[41] Choudary, B.M.; Chowdari, N.S.; Kantam, M. L.; Raghavan, K.V. Catalytic asymmetric dihydroxylation of olefins with new catalysts: the first example of heterogenization of OsO4_4~2-by ion-exchange technique. J Am Chem Soc, 2001, 123: 9220-9221.
[42] Chondary, B. M.; Chowdari, N.S.; Jyothi, K.; Kantam, M. L. Catalytic asymmetric dihydroxylation of olefins with reusable OsO_4~2 on ion-exchangers: the scopeand reactivity using various cooxidants. J Am Chem Soc, 2002, 124: 5341-5349.
[43] Yang, J. W.; Han, H.; Roh, E. J.; Lee, S.; Song, C.E. Osmium tetroxide anchored to porous resins bearing residual vingl groups: a highly active and recyclable solid for asymmetric dihydroxylation of olefins. Org Lett, 2002, 4 (26): 4685-4688.
[44] Dupont, J.; Souza, R. F.; Suorez, P. A. Ionic liquid (Molten Salt) phase organometallic catalysis. Chem Rev, 2002,102: 3667-3692.
[45] Branco, L. C.; Afonso, C.A.M. Catalytic asymmetric dihydroxylation of olefins using a recoverable and reusable OsO_4~2 in ionic liquid [bmim] [PF_6]. Chem Commun, 2002, 3036-3037.
[46] Song, C.E,; Jung, D.; Roh, E.J.; Lee S.; Chi, D.Y. Osmium tetroxide-(QN)_2PHAL in an ionic liquid: a highly efficient and recyclable catalyst system for asymmetric dihydroxylation of olefins. Chem Comm, 2002, 3038-3039.
[47] Santaniello, E., Manzocchi, A.; Sozzani, E Polyethylene glycols as host solvents: applications to organic synthesis, Tetrahedron Lett, 1979, (47): 4581-4582.
[48] Varma, R. S. Pure Appl Chem, 2001, 73:193
[49] Varma, R.S. in ACS Symp. Set. 7671 Green chemical synthese and processes, ed. Anastas, R.T., Heine, L.; Williamson, T. Ch 23, pp, 292-313, American Chemical Society, Washington D C, 2000.
[50] Varma, R. S.; Naicker, K. P.; Liesen, R J. Palladium chloride and tetraphenylphon ium bromide ilntercalated clay as a new catalyst for the Heck reaction. Tetrahedron Lett, 1999, 40 (11) : 2075-2078.
[51] Varma, R.S.; Naicker, K.R Synthesis of allybenzenes by cross-couling of allyl bromide with aryboronic acids using a palladium chloride and tetraphenyl phonium bromide intercalated clay catalyst. Green Chem, 1999,1(5): 247-250.
[52] Namboodiri, V. V.; Varma, R.S. Microwave-accelerated Suzuki cross-coupling reaction in polyethylene glyeol (PEG). Green Chem, 2001, 3: 146-148.
[53] Chandrasekhar, S.; Narsihmulu, Ch.; Sultana, S.S.; Reddy, N.R. Poly (ethylene glycol) (PEG) as a reusable solvent medium for organic synthesis: application in the Heck reaction. Org Left, 2002, 4 (25) :4399-4401.
[54] Chandrasekhar, S.; Narsihmulu,Ch.; Sultana, S. S. and Reddy, R. N. Osmium tetroxide in poly(ethylene glycol) (PEG): a recyclable reation medium for rapid asymmetric dihydroxylation under Sharpless condition. Chem Com., 20113, 1716
[55] Amberg, W.; Bennani, Y. L., Sharpless, K. B. Syntheses and crystal structures of the cinchona alkaloid derivatives used as ligands in the osmium-catalyzed asymmetric dihydroxylation of olefins. J Org Ch era, 1993, 58 (4):844～849.
[56] 匡永清，不对称二羟基化反应中新型可回收和重复使用的手性配体研究第四军医博士研究生学位论文，2002，59～60．
[57] Song, C, E., Yong, J. W., Sa, H. J. Efficient and practical polymericcatalysts for
heterogeneous asymmetric dihydroxylation of olefins. Tetrahedron Asymmetry, 1996, 7:645～648.
[58] Nagayama, S.; Endo, M.,; Kobayashi, S. Microencapsulated Osmium, Tetraoxide: A New Recoverable and Reusable Polymer-Supported Osmium Catalyst for Dihydroxylation of Olefins. J Org Chem, 1998, 63:6094-6095.
[59] Jacobsen, E. N., Marko, I., Mungall, W. S.; Schroder, G.; Sharpless, K. B. Asymmetric Dihydroxylation Via Ligand-Accelerated Catalysis. J A .Chem Soc, 1988,110:1968-1970.
[60] Dupont, J., Souza, R. F.; Suarez, P. A. Z. Ionic Liguid (Molten Salt) Phase Organometallic Catalysis. Chem Rev, 2002,102:3667-3692.
[61] Choong, Eui. Song.; Chun, Rim. Oh.;Eun, Joo. Roh.; Sang-gi Lee.One-stepsynthesis of placlitaxel side-chainprecursor:benzamide-based asymmetric aminohydroxylation of isopropyl trans-cinnamate. Tetrahedron asymmetry, 1999, (10): 671-674.
[62] Voronkov, M. V.; Gontcharov, A. V.; Wang, Z.M.lmproved large-scale synthesis of phenylisoserine and the taxol C_(13) side chain. Tetrahedron Letters, 2003, 44: 407-409.
[63] Amberg, W.; Bennani, Y. L.; Chadha, R.K.; Crispino, G.A; Sharpless, K.B. Synthese and crystal structures of cinchona alkaloid derivatives used as ligands in the osmium catalyzed asymmetric dihydroxylation of olefins. J Org Chem, 1993, 58: 844-849.
[64] 北京化学试剂公司，化学试剂目录手册，北京工业大学出版社，北京 1993。
[65] Rao, A. V. R.; Gurjar, M.K.; Joshi, S.V. Sharpless asymmetric dihydroxylation of aryloxy ethers. Tetrahedron Asymmetry 1990, 1(10): 693-696.
[2] Bolm, C.; Gerlach, A. Polymer-supported catalytic asymmetric Sharpless dihydrox ylations of olefins. Eur J Org Chem, 1998, 21-27.
[3] 张生勇，郭建全，《不对称催化反应》，北京，科学出版社，2002年．93．
[4] Criegee, R.;Marchand, B.;Wannvins, H. Justus Liebigs Ann Chem, 1942, 550: 99.
[5] Hentges, S. G.; Sharpless, K. B: Asymmetric induction in the reaction of osmium tetroxide with olefins. J Am Chem Soc, 1980, 102: 4263-4265.
[6] Wai, J. S. M.; Marko, I.; Svendsen, J. S.; Finn, M.G.; Jacobsen, E.N.; Sharpless, K.B. A mechanistic insight leads to a greatly improved osmium-catalyzed asymmetric dihydroxylation process. J Am Chem Soc, 1989, 111 (3): 1123-1125.
[7] Kwong, H. L.; Sorato, C.; Ogino, Y.; Chen, H.; Sharpless, K. B. Preclusion of the "second cycle"in the osmium-catalyzed asymmetric dihydroxylation of olefins leads to a superior process. Tetrahedron Lett. 1990,31 : 2999-3002.
[8] Gobel, T.; Sharpless, K.B. Angew chem Int Ed Engl, 1993, 32:1329.
[9] Sharpless, K.B.; Amberg, W.; Bennani, Y.L.; Crispino, G.A.; Hartung, J. The osmium-catalyzed asymmetric dihydroxylation: a new ligand class and a process improvement. J Org Chem, 1992, 57: 2768-2771.
[10] Kolb, H. C.; Andersson, R G.; Sharpless, K.B. Toward an understanding of the ligh enantioselectivity in the osmium catalyzed asymmetric dihydroxylation (AD).I. Kinetics, J Am Chem Soc, 1994, 116 (4) : 1278-1291.
[11] Amberg, W.; Bennani, Y. L.; Chadha, R.K.; Crispino, G. A.; Davis, W. D.; Hartung, J., Sharpless, K. B. Syntheses and crystal structures of the cinchona alkaloid derivatives used as ligands in the osmium-catalyzed asymmetric dihydroxylation of olefins, J Org Chem, 1993, 58 (4) : 844-849.
[12] Ogino, Y.; Chen, H.; Manoury, E.; Shibata, T.; Belier, M.; Lubben, D., Sharpless,
K. B. A ligand structure-enantioselectivity relationship for the osmium-catalyzed asymmetric dihydroxylation of olefins. Tetrahedron Lett, 1991, 32(41): 5761-5764.
[13] Crispino, G. A.; Jeong, K.S.; Kolb, H. C.; Wang, Z.M.; Xu, D.Q.; Sharpless, K. B. Improved enantioselectivity in asymmetric dihydroxylations of terminal olefins using pyrimidine ligands. J Org Chem, 1993, 58(15): 3785-3786.
[14] Becker, S.;King, S.B.; Taniguchi, M.; Vanhessche, K. P. M.; Sharpless, K. B. New Ligands and Improved Enantioselectivities for the Asymmetric Dihydroxylation of Olefins. J Org Chem, 1995, 60(13): 3940-3941
[15] Becker, H.; Sharpless, K. B. Angew Che Int. Ed Engl, 1996, 35: 448-451.
[16] Kim, B. M.; Sharpless, K. B Heterogeneous catalytic asymmetric dihydroxylation: Use of a polymer-bound alkaloid. Tetrahedron Let-t, 1990, 31(21) : 3003-3006.
[17] Pini, D.; Petri, A.; Salvado, P. Heterogeneous catalytic asymmetric dihydroxylation: Use of a polymerbound alkaloid, Tetrahedron Asymmetry, 1993, 4:2351-2353
[18] Pini, D.; Petri, A.; Salvadori, P. Heterogenous catalytic asymmetric dihydroxyla tion of olefins: A new polymeric support and a process improvement, Tetrahedron 1991, 50 (38): 11321-11328.
[19] Pini. D.; Petri, A.; Rapaccini, P.; Salvadori, P. Chirality,1995,7:580.
[20] Pini, D.; Petri, A.; Salvad ori, P. Heterogeneous enantioselective dihydroxylation of aliphatic olefins: A comparison between different polymeric cinchona alkaloid derivatives, Tetrahedron Left, 1995, 36(9): 1549-1552.
[21] Salvadori, P.; Pini, D.; Petri, A. In defense of the catalytic dsymmetric cis dihydroxylation of olefins utilizing insoluble polymeric ligands. J Am Chem Soc, 1997, 119 (29): 6929-6930.
[22] Lohray, B. B.; Thomas, A.; chittari, P.; Ahuja, J. R.; Dhal, P. K. Asymmetric dihydroxylation of alkenes on polymer support: Scope and limitation, Tetrahedron Left, 1992, 33 (37) : 5453-5456.
[23] Song, C. E.; Yang, J. W.; Sa, H. J.; Lee, S. Efficient and practical polymeric catalysts for heterogeneous asymmetric dihydroxylation of olefins, Tetrahedron
Asymmetry, 1996, 7(3): 645-648.
[24] Canali, L.; Song, C. E.; Sherrington, D. C. Polymer-supported bis-cinchona alkaloid ligands for asymmetric dihydroxylation of alkenes a cautionary tale, Tetrahedron: Asymmetry. 1998, 9:1029-1034.
[25] Lohray, B.B.; Nandanan, E; Bhushan, V. catalytic asymmetric dihydroxylation of alkenes using silicagel supported cinchona alkaloid. Tetrahedron Asymmetry, 1996, 7(10): 2805-2808.
[26] Song, C. E.; Yong, J. W.; Sa, H. J. Silicagel supported bis-cinchona alkaloid: a highly efficient chiral ligand for heterogeneous asymmetric dihydroxylation of olefins. Tetrahedron Asymmetry, 1997, 8 (6):841-844.
[27] Bolm, C.; Maischak.A.; Gerlach, A. Asymmetric dihydroxylation with silica-ancho-red alkaloids. Chem Commun, 1997, 24: 2353-2354.
[28] Lee, H.M., Kim, S. W.; Hyeon, T.;Kim, B. M. Asymmetric dihydroxylation using heterogenized cinchona alkaloid ligands on mesoporous Silica, Tetrahedron Asymmetry, 2001, 12: 1537-1541.
[29] Motorina, I.;Crudden, C.M. Asymmetric dihydroxylation ofolefins using cinchona alkaloids on highly ordered inorganic supports. Organic Lett, 2001, 3 (15):2325-2328.
[30] Han, H; Janda, K.D. Soluble polymer-Bound ligand-accelerated catalysis: asymm etric dihydroxylation. J Am Chem Soc, 1996, 118 (32): 7632-7633.
[31] Han, H.; Janda, K.D. A soluble polymer-bound approach to the sharpless catalytic asymmetric dihydroxylation (AD) reaction: preparation and application of a [(DHQD)_2-PHAL-PEG-OMe] ligand. Tetrahedron Lett, 1997, 38 (9): 1527-1530.
[32] Bolm, C.; Gerlach, A. Angew Chem Int Ed Engl. 1997, 36:1731.
[33] Bolm, C.; Maischak, A. Synlett, 2001,93.
[34] Bolm, C.; Marischak, A.; Gerlach, A. Asymmetric dihydroxylation with silica-anchored alkaloids. Chem Commun, 1997, 2353-2354.
[35] Kuang, Y. Q.; Zhang, S.Y.; Wei, L.L. A simple and effective soluble polymer-bou- nd ligand for the asymmetric dihydroxylation of olefins: DHQD-PHAL-OPEG-OMe. Tetrahedron Lett, 2001, 42 (34) :5925-5927.
[36] Kuang, Y. Q.; Zhang, S. Y.; Wei, L.L. A soluble block copolymer-supported bis-cinchona alkaloid ligand for the asymmetric dihydroxylation of olefins. Synth Commun, 2003, 33 (20):3543-3548.
[37] Kuang, Y. Q.; Zhang, S.Y.; Jiang, R.; Wei, L.L. A free ligand for the asymmetric dihydroxylation of olefins utilizing one-phase catalysis and two-phase separation. Tetrahedron Lett, 2002, 42 (20) : 3669-3671.
[38] Kobayshi, S.; Endo, M.; Nagayma, S. Catalytic asymmetric dihydroxylation of olefins using a recoverable and reusable polymer-supported osmium catalyst. J Am Chem Soc, 1999, 121: 11229-11230.
[39] Kobayashi, S.; Ishida, T.; Akiyama, R. Catalytic asymmetric dihydroxylation using phenoxy-ethoxymethyl-polystyrene (PEM)-based novel microencapsulated osmium tetroxide (PEM-Mc OsO_4).Org Lett, 2000, 3 (17) : 2649-2652.
[40] Ishida, T.; Akiyama, R.; Kobayash, S. Microencapsulated osmium tetroxide-cataly-zed asymmetric dihydroxylation of olefins in water without organic cosolvents. Adv Synth catal, 2003, 345: 576-579.
[41] Choudary, B.M.; Chowdari, N.S.; Kantam, M. L.; Raghavan, K.V. Catalytic asymmetric dihydroxylation of olefins with new catalysts: the first example of heterogenization of OsO4_4~2-by ion-exchange technique. J Am Chem Soc, 2001, 123: 9220-9221.
[42] Chondary, B. M.; Chowdari, N.S.; Jyothi, K.; Kantam, M. L. Catalytic asymmetric dihydroxylation of olefins with reusable OsO_4~2 on ion-exchangers: the scopeand reactivity using various cooxidants. J Am Chem Soc, 2002, 124: 5341-5349.
[43] Yang, J. W.; Han, H.; Roh, E. J.; Lee, S.; Song, C.E. Osmium tetroxide anchored to porous resins bearing residual vingl groups: a highly active and recyclable solid for asymmetric dihydroxylation of olefins. Org Lett, 2002, 4 (26): 4685-4688.
[44] Dupont, J.; Souza, R. F.; Suorez, P. A. Ionic liquid (Molten Salt) phase organometallic catalysis. Chem Rev, 2002,102: 3667-3692.
[45] Branco, L. C.; Afonso, C.A.M. Catalytic asymmetric dihydroxylation of olefins using a recoverable and reusable OsO_4~2 in ionic liquid [bmim] [PF_6]. Chem Commun, 2002, 3036-3037.
[46] Song, C.E,; Jung, D.; Roh, E.J.; Lee S.; Chi, D.Y. Osmium tetroxide-(QN)_2PHAL in an ionic liquid: a highly efficient and recyclable catalyst system for asymmetric dihydroxylation of olefins. Chem Comm, 2002, 3038-3039.
[47] Santaniello, E., Manzocchi, A.; Sozzani, E Polyethylene glycols as host solvents: applications to organic synthesis, Tetrahedron Lett, 1979, (47): 4581-4582.
[48] Varma, R. S. Pure Appl Chem, 2001, 73:193
[49] Varma, R.S. in ACS Symp. Set. 7671 Green chemical synthese and processes, ed. Anastas, R.T., Heine, L.; Williamson, T. Ch 23, pp, 292-313, American Chemical Society, Washington D C, 2000.
[50] Varma, R. S.; Naicker, K. P.; Liesen, R J. Palladium chloride and tetraphenylphon ium bromide ilntercalated clay as a new catalyst for the Heck reaction. Tetrahedron Lett, 1999, 40 (11) : 2075-2078.
[51] Varma, R.S.; Naicker, K.R Synthesis of allybenzenes by cross-couling of allyl bromide with aryboronic acids using a palladium chloride and tetraphenyl phonium bromide intercalated clay catalyst. Green Chem, 1999,1(5): 247-250.
[52] Namboodiri, V. V.; Varma, R.S. Microwave-accelerated Suzuki cross-coupling reaction in polyethylene glyeol (PEG). Green Chem, 2001, 3: 146-148.
[53] Chandrasekhar, S.; Narsihmulu, Ch.; Sultana, S.S.; Reddy, N.R. Poly (ethylene glycol) (PEG) as a reusable solvent medium for organic synthesis: application in the Heck reaction. Org Left, 2002, 4 (25) :4399-4401.
[54] Chandrasekhar, S.; Narsihmulu,Ch.; Sultana, S. S. and Reddy, R. N. Osmium tetroxide in poly(ethylene glycol) (PEG): a recyclable reation medium for rapid asymmetric dihydroxylation under Sharpless condition. Chem Com., 20113, 1716
[55] Amberg, W.; Bennani, Y. L., Sharpless, K. B. Syntheses and crystal structures of the cinchona alkaloid derivatives used as ligands in the osmium-catalyzed asymmetric dihydroxylation of olefins. J Org Ch era, 1993, 58 (4):844～849.
[56] 匡永清，不对称二羟基化反应中新型可回收和重复使用的手性配体研究第四军医博士研究生学位论文，2002，59～60．
[57] Song, C, E., Yong, J. W., Sa, H. J. Efficient and practical polymericcatalysts for
heterogeneous asymmetric dihydroxylation of olefins. Tetrahedron Asymmetry, 1996, 7:645～648.
[58] Nagayama, S.; Endo, M.,; Kobayashi, S. Microencapsulated Osmium, Tetraoxide: A New Recoverable and Reusable Polymer-Supported Osmium Catalyst for Dihydroxylation of Olefins. J Org Chem, 1998, 63:6094-6095.
[59] Jacobsen, E. N., Marko, I., Mungall, W. S.; Schroder, G.; Sharpless, K. B. Asymmetric Dihydroxylation Via Ligand-Accelerated Catalysis. J A .Chem Soc, 1988,110:1968-1970.
[60] Dupont, J., Souza, R. F.; Suarez, P. A. Z. Ionic Liguid (Molten Salt) Phase Organometallic Catalysis. Chem Rev, 2002,102:3667-3692.
[61] Choong, Eui. Song.; Chun, Rim. Oh.;Eun, Joo. Roh.; Sang-gi Lee.One-stepsynthesis of placlitaxel side-chainprecursor:benzamide-based asymmetric aminohydroxylation of isopropyl trans-cinnamate. Tetrahedron asymmetry, 1999, (10): 671-674.
[62] Voronkov, M. V.; Gontcharov, A. V.; Wang, Z.M.lmproved large-scale synthesis of phenylisoserine and the taxol C_(13) side chain. Tetrahedron Letters, 2003, 44: 407-409.
[63] Amberg, W.; Bennani, Y. L.; Chadha, R.K.; Crispino, G.A; Sharpless, K.B. Synthese and crystal structures of cinchona alkaloid derivatives used as ligands in the osmium catalyzed asymmetric dihydroxylation of olefins. J Org Chem, 1993, 58: 844-849.
[64] 北京化学试剂公司，化学试剂目录手册，北京工业大学出版社，北京 1993。
[65] Rao, A. V. R.; Gurjar, M.K.; Joshi, S.V. Sharpless asymmetric dihydroxylation of aryloxy ethers. Tetrahedron Asymmetry 1990, 1(10): 693-696.