手性聚合salen配体的设计合成及其在不对称催化反应中的应用
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摘要
本文设计合成了线型聚合salen和交联聚合salen两类N,O配体，研究了其Mn(Ⅲ)络合物催化的非官能化烯烃的不对称环氧化反应、Ti(Ⅳ)络合物催化的芳香醛的不对称硅腈化反应以及其Co(Ⅲ)络合物催化的末端环氧化合物的水解动力学拆分(HKR)。
一 poly-salenMn(Ⅲ)的合成及其在非官能化烯烃不对称环氧化反应中的应用
以邻叔丁基苯酚为原料，通过四步反应合成出了聚合salen配体L-1，研究了该配体的金属Mn(Ⅲ)络合物C-1对非官能化烯烃的不对称环氧化反应的催化作用。在NaClO／4-PPNO体系和m-CPBA／NMO体系中，对苯乙烯、cis-β-甲基苯乙烯和取代苯并吡喃类化合物，该类络合物表现出与其小分子母体催化剂相同的活性和光学选择性，对于6-溴-2,2-二甲基苯并吡喃，在m-CPBA／NMO体系中，使用4mol％的聚合物催化剂在30分钟内即可获得92％的分离收率和97％ee。在NaClO／4-PPNO体系中，该聚合物催化剂容易回收和循环使用，以2,2-二甲基苯并吡喃为底物，催化剂经过五次循环仍有63％的收率和95％ee。与我们以前报道的聚合物催化剂2-31、2-32相比，由于在聚合物链结上引入两个甲基，使得新催化剂的手性诱导能力大幅度提高。在催化剂循环过程中，虽然催化剂的活性和化学选择性略有降低，但所得产品的ee值保持不变。
二 poly-salenTi(Ⅳ)络合物对芳香醛的不对称硅腈化反应的催化作用
研究了poly-salen L-1的丁i(Ⅳ)络合物C-2对于芳香醛的不对称三甲基硅腈化反应的催化作用。在-40℃和1.0 mol％催化剂量下，以4-Cl-C_6H_4CHO为底物，获得了82％ee和98％收率的加成产物。20℃下催化剂循环使用6次后，仍能保持相近的对映体选择性。
三线型poly《）络合物对徽环氧化合物的HKR反应的催化作用
研究了poly｛）络合物C刁、C一对末端环氧化合物的水解动力学
拆分反应的催化作用。与不对称环氧化相似，络合物CS的手性诱导能力略好
于络合物C－4，使用 0．5 mol％的聚合物催化剂C3，对于 1）丙二醇、环氧氯
丙烷以及苯氧基环氧丙烷等。可分别获得98％ee、97％ee、98％ee的手性目
标产物。更重要的是，在环氧氯丙烷的水解动力学拆分中，观察到聚合物催化
剂参与反应形成亲水性末端的现象，这使催化剂分离回收更加简便，回收催化
剂在十定条件下表现出相近的活性和更好的手性诱导能力。
四。交联Poly七alm）络合物的设计合成及其在末端环氧化合物的HKR中
；，的应用
以几种易得的骏酸为骨架，设计合成出了相应的双水杨醛和三水杨醛S－3、
S－4、S－5，将双水杨醛 S－3和三水杨醛 S－4按不同比例混合后再与手性环己二
胺缩合制备出交联聚合物配体，该配体与CO（ll）络合后得到交联聚合物催化剂。
研究了其对环氧苯乙烷、环氧氯丙烷以及苯氧基环氧丙烷等的水解动力学拆分
的催化作用。结果表明，交联聚合物催化剂表现出更高的活性和极高的手性诱
导能力。在 0刀2o．16 mol％的催化剂用量下，高效、高选择性的完成反应，获
得高达 99％ee的手性目标产物。
In this thesis, linear and crosslinked polymeric salen ligands were prepared, and their Mn(III) complexes, Ti(IV) complexes and Co(III) complexes were used in the asymmetric epoxidation of unfunctionalized olefins, the asymmetric trimethylsilylcyanation of aromatic aldehydes and the hydrolytic kinetic resolution (HKR) of terminal epoxides.
1. Synthesis of poly-salenMn(III) complex and its application in the asymmetric epoxidation of unfunctionalized olefins
Begin from 2-f-Butyl-phenol, a novel chiral poly-salen ligand L-l was synthesized in four steps, whose Mn(III) complex C-l was employed in the asymmetric epoxidation of unfunctionalized olefins. In the NaCIO / 4-PPNO or W2-CPBA / NMO systems, using styrene, (Z)-p-methylstyrene and substituted 2,2-dimethylchromenes as substrates, catalyst C-l exhibited the same activities and enantioselectivities as its parent monomer catalyst. In the w-CPBA / NMO system, 6-Br-2,2-dimethylchromene as the substrate, up to 92 % isolated yield and 97 % ee were obtained with 4 mol % polymeric catalyst in 30min. Furthermore, the polymeric catalyst could be easily recovered and recycled efficiently for several
times in the NaCIO / 4-PPNO svstem. after five reactions. 95 % ee and 63 %
isolated yield of epoxide were obtained using 2,2-dimethylchromene as the substrate. Compared with the polymeric catalysts 2-31, 2-32 we reported before, the new polymeric catalyst have the best enantioselectivities because of the introduction of two geminal methyl groups on the linking carbon atom. In the recycling experiments, the new polymeric catalyst kept its enantioselectivities.
2 Asymmetric trimethylsilylcyanation of aromatic aldehydes catalyzed by poly-salenTi(IV) complex
A poly-salen-Ti complex C-2 derived from L-l was used as catalyst for the catalytic asymmetric trimethylsilylcyanation of aromatic aldehydes. At -40℃, with 1 mol % of polymeric catalyst C-2, the adduct of 4-CH3-C6H4CHO was obtained in 82 % ee and 98 % yield. The polymeric catalyst could be recycled for six times with the same enantioselectivity.
3 The HKR of terminal epoxides catalyzed by chiral poly-salenCo(III) complexes
Poly-salen.Co(III) complexes C-3, C-4 were employed in the HKR of terminal epoxides. As that observed in the asymmetric epoxidation of olefins, polymeric catalyst C-3 showed better enantioselectivities, the ees were 98 %, 97 % and 98 % respectively for 1,2-propane diol, epichlorohydrin and phenyl glycidyl ether with 0.5 mol, % mol of C-3. In the HKR of epichlorohydrin, we found that the polymeric catalysts reacted with the substrate to form hydrophilic ends, which simplified the separation and the recovery of the polymeric catalysts. The recovered catalyst showed better enantioselectivities in some conditions.
4 The design, synthesis of crosslinked poly-salenCo(III) complexes and their
application in the HKR of terminal epoxides
Di-salicylaldehydes and tri-salicylaldehydes S-3, S-4, S-5 were synthesized from some easily prepared acids. The crosslinked polymeric ligands could be prepared by condensation of (R,R)-1,2-cyclohexanediamine stoichiometrically with a mixture of S-3 and S-4 in different proportions, polymeric catalysts were obtained by inserting the Co atoms to the ligands. These catalysts were employed in the HKR of epichlorohydrin, styrene oxide and phenyl glycidyl ether. The results showed that the crosslinked polymeric catalysts had better activities in a proper range of crosslinker's proportions, up to 99 % ee were obtained, using only 0.02-0.16 mol % of polymeric catalysts (based on catalytic unit).
一 poly-salenMn(Ⅲ)的合成及其在非官能化烯烃不对称环氧化反应中的应用
以邻叔丁基苯酚为原料，通过四步反应合成出了聚合salen配体L-1，研究了该配体的金属Mn(Ⅲ)络合物C-1对非官能化烯烃的不对称环氧化反应的催化作用。在NaClO／4-PPNO体系和m-CPBA／NMO体系中，对苯乙烯、cis-β-甲基苯乙烯和取代苯并吡喃类化合物，该类络合物表现出与其小分子母体催化剂相同的活性和光学选择性，对于6-溴-2,2-二甲基苯并吡喃，在m-CPBA／NMO体系中，使用4mol％的聚合物催化剂在30分钟内即可获得92％的分离收率和97％ee。在NaClO／4-PPNO体系中，该聚合物催化剂容易回收和循环使用，以2,2-二甲基苯并吡喃为底物，催化剂经过五次循环仍有63％的收率和95％ee。与我们以前报道的聚合物催化剂2-31、2-32相比，由于在聚合物链结上引入两个甲基，使得新催化剂的手性诱导能力大幅度提高。在催化剂循环过程中，虽然催化剂的活性和化学选择性略有降低，但所得产品的ee值保持不变。
二 poly-salenTi(Ⅳ)络合物对芳香醛的不对称硅腈化反应的催化作用
研究了poly-salen L-1的丁i(Ⅳ)络合物C-2对于芳香醛的不对称三甲基硅腈化反应的催化作用。在-40℃和1.0 mol％催化剂量下，以4-Cl-C_6H_4CHO为底物，获得了82％ee和98％收率的加成产物。20℃下催化剂循环使用6次后，仍能保持相近的对映体选择性。
三线型poly《）络合物对徽环氧化合物的HKR反应的催化作用
研究了poly｛）络合物C刁、C一对末端环氧化合物的水解动力学
拆分反应的催化作用。与不对称环氧化相似，络合物CS的手性诱导能力略好
于络合物C－4，使用 0．5 mol％的聚合物催化剂C3，对于 1）丙二醇、环氧氯
丙烷以及苯氧基环氧丙烷等。可分别获得98％ee、97％ee、98％ee的手性目
标产物。更重要的是，在环氧氯丙烷的水解动力学拆分中，观察到聚合物催化
剂参与反应形成亲水性末端的现象，这使催化剂分离回收更加简便，回收催化
剂在十定条件下表现出相近的活性和更好的手性诱导能力。
四。交联Poly七alm）络合物的设计合成及其在末端环氧化合物的HKR中
；，的应用
以几种易得的骏酸为骨架，设计合成出了相应的双水杨醛和三水杨醛S－3、
S－4、S－5，将双水杨醛 S－3和三水杨醛 S－4按不同比例混合后再与手性环己二
胺缩合制备出交联聚合物配体，该配体与CO（ll）络合后得到交联聚合物催化剂。
研究了其对环氧苯乙烷、环氧氯丙烷以及苯氧基环氧丙烷等的水解动力学拆分
的催化作用。结果表明，交联聚合物催化剂表现出更高的活性和极高的手性诱
导能力。在 0刀2o．16 mol％的催化剂用量下，高效、高选择性的完成反应，获
得高达 99％ee的手性目标产物。
In this thesis, linear and crosslinked polymeric salen ligands were prepared, and their Mn(III) complexes, Ti(IV) complexes and Co(III) complexes were used in the asymmetric epoxidation of unfunctionalized olefins, the asymmetric trimethylsilylcyanation of aromatic aldehydes and the hydrolytic kinetic resolution (HKR) of terminal epoxides.
1. Synthesis of poly-salenMn(III) complex and its application in the asymmetric epoxidation of unfunctionalized olefins
Begin from 2-f-Butyl-phenol, a novel chiral poly-salen ligand L-l was synthesized in four steps, whose Mn(III) complex C-l was employed in the asymmetric epoxidation of unfunctionalized olefins. In the NaCIO / 4-PPNO or W2-CPBA / NMO systems, using styrene, (Z)-p-methylstyrene and substituted 2,2-dimethylchromenes as substrates, catalyst C-l exhibited the same activities and enantioselectivities as its parent monomer catalyst. In the w-CPBA / NMO system, 6-Br-2,2-dimethylchromene as the substrate, up to 92 % isolated yield and 97 % ee were obtained with 4 mol % polymeric catalyst in 30min. Furthermore, the polymeric catalyst could be easily recovered and recycled efficiently for several
times in the NaCIO / 4-PPNO svstem. after five reactions. 95 % ee and 63 %
isolated yield of epoxide were obtained using 2,2-dimethylchromene as the substrate. Compared with the polymeric catalysts 2-31, 2-32 we reported before, the new polymeric catalyst have the best enantioselectivities because of the introduction of two geminal methyl groups on the linking carbon atom. In the recycling experiments, the new polymeric catalyst kept its enantioselectivities.
2 Asymmetric trimethylsilylcyanation of aromatic aldehydes catalyzed by poly-salenTi(IV) complex
A poly-salen-Ti complex C-2 derived from L-l was used as catalyst for the catalytic asymmetric trimethylsilylcyanation of aromatic aldehydes. At -40℃, with 1 mol % of polymeric catalyst C-2, the adduct of 4-CH3-C6H4CHO was obtained in 82 % ee and 98 % yield. The polymeric catalyst could be recycled for six times with the same enantioselectivity.
3 The HKR of terminal epoxides catalyzed by chiral poly-salenCo(III) complexes
Poly-salen.Co(III) complexes C-3, C-4 were employed in the HKR of terminal epoxides. As that observed in the asymmetric epoxidation of olefins, polymeric catalyst C-3 showed better enantioselectivities, the ees were 98 %, 97 % and 98 % respectively for 1,2-propane diol, epichlorohydrin and phenyl glycidyl ether with 0.5 mol, % mol of C-3. In the HKR of epichlorohydrin, we found that the polymeric catalysts reacted with the substrate to form hydrophilic ends, which simplified the separation and the recovery of the polymeric catalysts. The recovered catalyst showed better enantioselectivities in some conditions.
4 The design, synthesis of crosslinked poly-salenCo(III) complexes and their
application in the HKR of terminal epoxides
Di-salicylaldehydes and tri-salicylaldehydes S-3, S-4, S-5 were synthesized from some easily prepared acids. The crosslinked polymeric ligands could be prepared by condensation of (R,R)-1,2-cyclohexanediamine stoichiometrically with a mixture of S-3 and S-4 in different proportions, polymeric catalysts were obtained by inserting the Co atoms to the ligands. These catalysts were employed in the HKR of epichlorohydrin, styrene oxide and phenyl glycidyl ether. The results showed that the crosslinked polymeric catalysts had better activities in a proper range of crosslinker's proportions, up to 99 % ee were obtained, using only 0.02-0.16 mol % of polymeric catalysts (based on catalytic unit).
引文
1. (a) E. N. Jacobsen, A. Pfaltz and H. Yamamoto, Comprehensive Asymmetric Catalysis, 2nd edn., Springer-Verlag, Belin, Heidelberg, New York, 1999. (b)林国强，陈耀全，陈新滋，李月明著，手性合成—不对称反应及其应用，科学出版社，2000年．
2. De Vos, D. E.; Vankelecom, I. F. J.; Jacobs, P. A. Chiral Catalyst Immobilization and Recycling, Wiley-VCH, Weinheim, New York, Chichester. 2000.
3. Dumont, W.; Poulin, J. C.; Dang, T. P.; Kagan, H. B. J. Am. Chem. Soc. 1973, 95, 8295.
4. (a) Takaishi, N.; Imai, H.; Bertelo, C. A.; Stille, J, K.; J. Am. Chem. Soc. 1978,
100, 264. (b) Masuda, T.; Stille, J. K.; J. Am. Chem. Soc. 1978, 100, 268.
5. Bayston, D. J.; Fraser, J. L.; Ashton, M. R.; Baxter, A. D.; Polywka, M. E. C.;Moses, E. J. Org. Chem. 1998, 63, 3137.
6. (a) Malmstrom, T.; Andersson, C. J. Mol. Catal. A." Chem. 1999, 139, 259. (a) Malmstrom, T.; Andersson, C. J. Mol. Catal. A." Chem. 2000,157, 79.
7. Fan, Q. H.; Ren, C. Y.; Yeung, C. H.; Hu, W. H.;Chan, A. S. C. J. Am. Chem. Soc. 1999, 121, 7407.
8. (a) Selke, R,; Haupke, K.; Krause, H. W. J. Mol. Catal. A. Chem. 1989, 56, 315. (b) Toth, I.; Hanson, B. E.; Davis, M. E. J.. Organometal. Chem. 1990, 397, 109,
9. Locatelli, F.; Gamez, P.; Lemaire, M. J. Mol. Catal. A: Chem. 1998, 135, 89.
10. (a) Polborn, K.; Severin, K. Chem. Commun. 1999, 2481. (b) Polborn, K.; Severin, K. Chem. Eur. J. 2000, 6, 4604. (c) Polborn,K.; Severin, K. Eur. J. Inorg. Chem. 2000, 1687.
11. Nozaki, K.; Shibahara, F.; Itoi, Y.; Shirakawa, E.; Ohta, T.; Takaya, H.; Hiyama, T. Bull. Chem. Soc. Jpn. 1999, 72, 1911.
12. Bergbreiter, D. E.; Poteat, J.; Zhang, L. React. Polym. 1993, 20, 99.
13. (a).Hu, Q.S,; Huang, W. S.; Pu, L. J. Org. Chem. 1998, 63, 2798. (b) Huang, W. S.; Hu, Q. S.; Pu, L. J. Org. Chem. 1999, 64, 7940.
14. (a)Rheiner,P. B.; Sellner, H.; Seebach, D. Helv. Chim. Acta 1997, 80, 2027. (b) Sellner, H.; Seebach, D. Angew. Chem., Int. Ed Engl. 1999, 38, 1918. (c) Sellner, H.; Faber, C.; Rheiner.P. B.; Seebach, D. Chem. Eur. J. 2000, 6, 3692.
15. Briggs, J. C.; Hodge, P.; Zhang, Z. P. React. Polym. 1993,19, 73.
16. Gilbertson, S. R.; Wang, X. F.; Hoge, G. H.; Klug, C. A.; Schaefer, J. Organometallics 1996, 15, 4678.
17．姚小泉 中科院大连化物所1997级博士学位论文 2000．
18. a)Joseph, M. R.; Jacobsen, E. N. J. Am. Chem. Soc. 2001, 123, 2687-2688. b) Ready, J. M.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2002, 41, 1374-1377.
2. De Vos, D. E.; Vankelecom, I. F. J.; Jacobs, P. A. Chiral Catalyst Immobilization and Recycling, Wiley-VCH, Weinheim, New York, Chichester. 2000.
3. Dumont, W.; Poulin, J. C.; Dang, T. P.; Kagan, H. B. J. Am. Chem. Soc. 1973, 95, 8295.
4. (a) Takaishi, N.; Imai, H.; Bertelo, C. A.; Stille, J, K.; J. Am. Chem. Soc. 1978,
100, 264. (b) Masuda, T.; Stille, J. K.; J. Am. Chem. Soc. 1978, 100, 268.
5. Bayston, D. J.; Fraser, J. L.; Ashton, M. R.; Baxter, A. D.; Polywka, M. E. C.;Moses, E. J. Org. Chem. 1998, 63, 3137.
6. (a) Malmstrom, T.; Andersson, C. J. Mol. Catal. A." Chem. 1999, 139, 259. (a) Malmstrom, T.; Andersson, C. J. Mol. Catal. A." Chem. 2000,157, 79.
7. Fan, Q. H.; Ren, C. Y.; Yeung, C. H.; Hu, W. H.;Chan, A. S. C. J. Am. Chem. Soc. 1999, 121, 7407.
8. (a) Selke, R,; Haupke, K.; Krause, H. W. J. Mol. Catal. A. Chem. 1989, 56, 315. (b) Toth, I.; Hanson, B. E.; Davis, M. E. J.. Organometal. Chem. 1990, 397, 109,
9. Locatelli, F.; Gamez, P.; Lemaire, M. J. Mol. Catal. A: Chem. 1998, 135, 89.
10. (a) Polborn, K.; Severin, K. Chem. Commun. 1999, 2481. (b) Polborn, K.; Severin, K. Chem. Eur. J. 2000, 6, 4604. (c) Polborn,K.; Severin, K. Eur. J. Inorg. Chem. 2000, 1687.
11. Nozaki, K.; Shibahara, F.; Itoi, Y.; Shirakawa, E.; Ohta, T.; Takaya, H.; Hiyama, T. Bull. Chem. Soc. Jpn. 1999, 72, 1911.
12. Bergbreiter, D. E.; Poteat, J.; Zhang, L. React. Polym. 1993, 20, 99.
13. (a).Hu, Q.S,; Huang, W. S.; Pu, L. J. Org. Chem. 1998, 63, 2798. (b) Huang, W. S.; Hu, Q. S.; Pu, L. J. Org. Chem. 1999, 64, 7940.
14. (a)Rheiner,P. B.; Sellner, H.; Seebach, D. Helv. Chim. Acta 1997, 80, 2027. (b) Sellner, H.; Seebach, D. Angew. Chem., Int. Ed Engl. 1999, 38, 1918. (c) Sellner, H.; Faber, C.; Rheiner.P. B.; Seebach, D. Chem. Eur. J. 2000, 6, 3692.
15. Briggs, J. C.; Hodge, P.; Zhang, Z. P. React. Polym. 1993,19, 73.
16. Gilbertson, S. R.; Wang, X. F.; Hoge, G. H.; Klug, C. A.; Schaefer, J. Organometallics 1996, 15, 4678.
17．姚小泉 中科院大连化物所1997级博士学位论文 2000．
18. a)Joseph, M. R.; Jacobsen, E. N. J. Am. Chem. Soc. 2001, 123, 2687-2688. b) Ready, J. M.; Jacobsen, E. N. Angew. Chem. Int. Ed. 2002, 41, 1374-1377.