The use of Chiral Ketones /Aldehydes in the Asymmetric Epoxidation of lefins Somnath Bhattacharjee Michigan State University 12th January, 2005
Introduction
Sharpless Asymmetric Epoxidation 3 C C 2 (-)-diethyl tartrate Ti(-i-Pr) 4, t Bu (+)-diethyl tartrate Ti(-i-Pr) 4, t Bu 3 C Gao, Y.; anson, R. M.; Klunder, J. M.; Ko, S. Y.; Masamune,.; Sharpless, K. B. J. Am. Chem. Soc. 1987, 109, 5765. Rossiter, B. E.; Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1981, 103, 464. (2R, 3R) 58% yield, 95% ee 3 C (2S, 3S) 70% yield, 92% ee
Jacobsen Asymmetric Epoxidation C 2 5 2 C Catalyst, 3 mol % C 2 5 2 C NaCl 81% yield, 87% ee. N + Mn PF 6 - N Chang, S.; Lee, N..; Jacobsen, E. N. J. rg. Chem. 1993, 58, 6939.
Dioxirane Catalyzed Epoxidation C 2 Cl 2-2 KS 5 + + Bu 4 NS 4 R 3 R 2 R 4 R 2 1 S 5 R 3 R 2 R 4 4 R 2 S 3 2 R 2 S 4 2 S 3 R 2 3 Schulz, M.; Liebsch, S.; Kluge, R.; Adam, W. J. rg. Chem. 1997, 62, 188. Curci, R.; Fiorentino, M.; Troisi, L.; Edwards, J..; Pater, R.. J. rg. Chem. 1980, 45, 4758.
Activities of Various ketones in Catalyzing in situ Epoxidation of trans-stilbene Catalyst xone/nac 3 C 3 CN/ 2 rt, p 7-7.5 R 2 catalyst 1 Catalyst Entry R 2 reaction time (min) 1. C 3 C 3 300 2. C 3 CF 3 < 4 3. C 3 C 2 F 20 4. CF 3 70 Yang, D.; Yip, Y. C.; Tang, M. W.; Wong, M.; Zheng, J.; Cheung, K. J. Am. Chem. Soc. 1996, 118, 491-492.
First Example of Ketone-Catalyzed Asymmetric Epoxidation Catalyst xone/nac 3 C 3 CN/ 2 rt, p 7-7.5 1 2 Me Entry ketone yield ee config. (equiv) (%) (%) F 3 C C 3 1. 1 (2.0) 60 11 (+)-(1R,2R) 2. 2 (1.0) 85 9.5 (+)-(1R,2R) 3. 3 (1.0) 82 13 (+)-(1R,2R) 4. 4 (1.0) 77 18 (+)-(1R,2R) CF 3 3 4 Catalyst Curci, R.; D' Accolti, L.; Fiorention, M.; Rosa, A. Tetrahedron Lett. 1995, 36, 5831. Adam, W.; Curci, R.; Edwards, J. Acc. Chem. Res. 1989,22, 205. Curci, R.; Fiorentino, M.; Serio, M. R. J. Chem. Soc., Chem. Commun. 1984, 155.
Chiral Ketones with C 2 Symmetry for Asymmetric Epoxidation
Asymmetric Epoxidation of Unfunctionalized lefins Catalyzed by Ketone 1 47% ee (-)-(S,S) 87% ee (-)-(S,S) 50% ee (+)-(S) Yang, D.; Yip, Y. C.; Tang, M. W.; Wong, M. K.; Zeng, J..; Cheung, K. K. J. Am. Chem. Soc. 1996, 118, 491-492.
The Spiro and Planar Transition States for the Dioxirane Epoxidation of lefins R' R R' R R' R xygen non-bonding orbital R' R xygen non-bonding orbital lefin π * orbital lefin π * orbital Spiro T.S Planar T.S Wang, Z.; Tu, Y.; Frohn, M.; Zhang, J.; Shi, Y. J. Am. Chem. Soc. 1997,119, 11224-11235.
Proposed Spiro Transition State for the epoxidation of trans olefins (S, S) A (R, R) B Spiro 1 Favored Spiro 2 disfavored Yang, D.; Wong, M.; Yip, Y.; Wang, X. Tang, M.; Zheng, J.; Cheung, K. J. Am. Chem. Soc. 1998, 120, 5943-5952.
Proposed Planar Transition State for the epoxidation of trans olefins (S, S) A (R, R) B Planar 1 favored Planar 2 disfavored Yang, D.; Wong, M.; Yip, Y.; Wang, X. Tang, M.; Zheng, J.; Cheung, K. J. Am. Chem. Soc. 1998, 120, 5943-5952.
Asymmetric Epoxidation of Unfunctionalized lefins Catalyzed by Ketones Catalyst xone/nac 3 C 3 CN/ 2 rt, p 7-7.5 (S, S) A 3 3' (R)-1 X X 1. X= 2. X= Cl 3. X= Br 4. X= I 5. X= C 2 C 3 Entry Catalyst yield (ee) (%) Config. 1. (R)-1 91 (47) (-)-(S,S) 2. (R)-2 95 (76) (-)-(S,S) 3. (R)-3 92 (75) (-)-(S,S) 4. (R)-4 90 (32) (-)-(S,S) 5. (R)-6 92 (66) (-)-(S,S) Yang, D.; Wang, X.; Wong, M., Yip, Y.; Tang, M. J. Am. Chem. Soc. 1996, 118, 11311-11312.
New Approaches for Asymmetric Epoxidation of trans lefin 10 mole % (S)-6 xone, K 2 C 3 DME- 2 C F F 1 Song 2 Denmark Catalyst Mol (%) Time (h) Temp ( o C) Yield (%) ee (%) 1 100 25 25 95 29 2 10 10 0 55-2 30 10 0 80 88 Song, C. E.; Lee, K. C.; Lee, S; Jin, B. W. Tetrahedron: Asymmetry. 1997, 8, 2921-2926. Denmark, S. E.; Wu, Z. Synlett 1999, 847-859.
ypothetical Transition Structures for Approach of Alkenes to Dioxirane of (-)-2 R b R' a R R' Me Me F F Denmark, S. E.; Matsuhashi,. J. rg. Chem. 2002, 67, 3479-3486.
Behar s Approach to Improve the Enantioselectivity for Asymmetric Epoxidation F F R 2R1 3 Denmark Behar 4., R 2, R 3, R 4 = 5., R 3, R 4 =, R 2 = F 6., R 3 =, R 2, R 4 = F 7., R 2, R 3 = F, R 4 = 8., R 2, R 3, R 4 = F R 4 R 3 Catalyst Mol (%) Time (h) Temp ( o C) Yield (%) ee (%) 3. 30 10 0 80 88 4. 10 4-15 35 46 5. 10 4-15 57 80 6. 10 3.5-15 100 86 7. 10 3.5-15 100 83 8. 10 3.5-15 32 40 Stearman, J. C.; Behar, V. Tetrahedron. Lett. 2002, 43, 1943-1946.
Summary F R 3 F 1 Song Behar 3 Cl F F (R)-3 3' Cl 2 Denmark
Fructose-derived Chiral Ketones for Epoxidation
Fructose-derived Ketone Catalyst for the Asymmetric Epoxidation of trans Stilbene xone, 2 -C 3 CN p 7-7.5 1 d entry Time (h) Isolated Yield (%) ee (%) 1. 1 31 > 95 2. 2 39 > 95 3. 3 40 89 4. 4 47 85 Wang, Z.; Tu, Y.; Frohn, M.; Zhang, J.; Shi, Y. J. Am. Chem. Soc. 1997,119, 11224-11235.
Possible Reaction Pathway of Ketone 1 R 3 R 2 S 5 R 2 R 3 1 4 Baeyer-Villiger Reaction S 3 2 2 S 4 S 3 + 3 5 6 ydrolysis Wang, Z.; Tu, Y.; Frohn, M.; Zhang, J.; Shi, Y. J. Am. Chem. Soc. 1997,119, 11224-11235.
Baeyer-Villiger Reaction R 2 2 R ' R R ' Mechanism 2 R R ' R R' G 2 R R ' Example 2 2 F + F F 71% E 29% F Renz, M.; Meunier, B.; Eur. J. rg. Chem. 1999, 737 Crudden, C. M.; Chen, A. C.; Calhoun, L. A.Angew. Chem., Int. Ed. 2000, 39, 2852
Effect of p in Ketone Catalyzed Epoxidation xone, 2 -C 3 CN p 7-7.5 R 3 R 2 S 5 Catalyst 1 R 3 R 2 4 1 Baeyer-Villiger Reaction S 3 2 2 S 4 p 7-7.5 p 10.5-11.5 entry Time (h) Yield (ee) (%) Yield (ee)(%) 1. 4 47 (85) 86 (>95) S 3 3 + 5 6 ydrolysis Frohn, M.; Wang, Z.; Shi, Y. J. rg. Chem. 1998, 63, 6425-6426.
Approaches to Circumvent Baeyer-Villiger Reaction 4 2 mcpba + 1 2 3 major Ac Ac 4 5 Epoxidation by catalyst 5 Entry Substrate Yield (%) ee (%) config. 1. 2. 3. 4. 5. Et C 2 Et C 2 Et C 2 Et C 2 Et C 2 Et 73 96 (+)-(2S,3R) 91 93 (+) 64 82 (+) 77 89 (+) 96 94 (+) 6. C 2 Et 84 44 (-)-(2S,3S) Wu, X.; She, X.; Shi, Y. J. Am. Chem. Soc. 2002, 124, 8792-8793.
Comparison Between Ketones 1 and 5 Ac Ac 1 5 Ketone 1 Ketone 5 Entry Substrate Yield (ee) (%) Yield (ee) (%) config. 1. 94 (95.5) 81 (83) (R, R) 2. 85 (97.9) 67 (96) (R, R) 3. TBS 87 (94) 73 (94) (R, R) Me 4. 80 (93) (R, R) 89 (95.5) 5. 94 (98) 93 (92) (R, R) Tian,.; She, X.; Shi, Y. rganic Lett. 2001, 3, 715-718
Transition State Analysis for the Epoxidation of trans lefin by Ketone 1 Catalyst xone/nac 3 C 3 CN/ 2 rt (R, R) (R, R) Spiro 1 Favored 1 Planar 1 disfavored Spiro 2 disfavored (S, S) 2 Planar 2 Favored Tu, Y.; Wang, Z.' Shi, Y. J. Am. Chem. Soc. 1996, 118, 9806-9807.
Asymmetric Epoxidation of Trisubstituted lefin by Ketone 1 xone, R R 3 3 2 -C 3 CN R 1 R 2 R 2 p 11, catalyst 1 (catalyst) Entry Substrate Yield (%) ee (%) Config. 1. 2. 89 96.8 (R,R) 93 76.4 (+)-(R) 3. 89 95.5 (+)-(R,R) Wang, Z.; Tu, Y.; Frohn, M.; Zhang, J.; Shi, Y. J. Am. Chem. Soc. 1997, 119, 11224-11235.
Transition State Analysis for the Epoxidation of Trisubstituted lefins xone, R R 3 3 2 -C 3 CN R 1 R 2 R 2 p 11, catalyst 1 (catalyst) R 3 R 2 Spiro 1 Favored R 2 R3 Spiro 2 disfavored R 3 R 2 R 1 Major 1 R 3 R 2 Planar 1 disfavored R 1 R 2 R 3 Planar 2 disfavored Wang, Z.; Tu, Y.; Frohn, M.; Zhang, J.; Shi, Y. J. Am. Chem. Soc. 1997, 119, 11224-11235.
Transition State Analysis for the Epoxidation of Trisubstituted lefin by Ketone 1 xone, R R 3 3 2 -C 3 CN R 1 R 2 R 2 p 11, catalyst 1 (catalyst) R 3 R 2 R 3 Spiro 4 disfavored R 2 R 3 Spiro 3 disfavored R 3 R 2 Planar 3 disfavored minor R 2 R 3 Planar 4 Favored R2 Wang, Z.; Tu, Y.; Frohn, M.; Zhang, J.; Shi, Y. J. Am. Chem. Soc. 1997, 119, 11224-11235.
Effects of the Size of Substituents on Enantioslectivity R 3 R 3 R 2 R R 2 1 Major R 3 R 2 minor R 3 R2 Spiro 1 Effect of the size of Planar 4 26% ee 79% ee 81% ee Effect of the size of R 3 ee increases as the size of decreases C 10 21 86.5% ee 91% ee ee increases as the size of R 3 increase Wang, Z.; Tu, Y.; Frohn, M.; Zhang, J.; Shi, Y. J. Am. Chem. Soc. 1997, 119, 11224-11235.
Epoxidation of cis and Terminal lefins by Ketone 1 Entry Subtrate Yield (%) ee (%) Config. 1 (catalyst) 1. 2. 3. 92 12 (-)-(1S,2R) 43 61.4 (+)-(R,R) 90 24.3 (+)-(R) 4. C 8 17 92 17 (+)-(R) 5. 95 19.6 (-)-(S) Wang, Z.; Tu, Y.; Frohn, M.; Zhang, J.; Shi, Y. J. Am. Chem. Soc. 1997,119, 11224-11235.
Transition State Analysis for cis and Terminal lefins cis lefin Terminal lefins R 2 R 3 1 spiro 1 Spiro 3 Planar 3 R 3 R 2 2 spiro 2 Spiro 4 Planar 4 Wang, Z.; Tu, Y.; Frohn, M.; Zhang, J.; Shi, Y. J. Am. Chem. Soc. 1997, 119, 11224-11235.
Summary Advantages: Enantioselctivity is high for trans and tri substitued olefins. Disadvantages: Enantioselectivity is very low for cis and terminal olefins. 1 Ac Ac Effective catalyst for elctron deficient olefins. 5
Transition State Analysis to Design new Catalyst for cis lefins Me Me Spiro 1 Spiro 2 X Y Me X Y Me Spiro 3 Spiro 4 Tian,.; She, X.; Shu, L.; Yu,.; Shi, Y. J. Am. Chem. Soc. 2000, 122, 11551-11552.
6, xone Fructose-derive new Catalyst for the Epoxidation of cis lefins Up to 97% ee Entry Substrate Yield (%) ee (%) Config. 1. 87 91 (-)-(1R,2S) Boc N 6 2. 91 92 (-)-(1R,2S) 3. 77 91 (-)-(5R,6S) 4. 82 91 (-)-(2S,3R) 5. 61 97 (+) Tian,.; She, X.; Yu,.; Shu, L.; Shi, Y. J. rg. Chem. 2002, 67, 2435-2446
Transition State Analysis for the Epoxidation of cis lefins NBoc Ar R NBoc R Ar Spiro 1 Spiro 2 NBoc NBoc R Ar Ar R Planar 1 Planar 2 Tian,.; She, X.; Yu,.; Shu, L.; Shi, Y. J. rg. Chem. 2002, 67, 2435-2446
Catalyst 6 for the Epoxidation of Terminal lefins R 6, xone R Up to 85 % ee Entry Substrate Yield (%) ee (%) Config. 1. 100 81 (-)-(R) 2. 86 84 (-)-(R) Boc N 6 3. 93 71 (-) NBoc NBoc NBoc Spiro 1 Spiro 2 Planar 1 Tian,.; She, X.; Shi, Y. rg. lett. 2001, 5, 1929-1931.
Comparison Between Ketone Catalysts 1 and 6 Entry Substrate ketone Yield (ee) (%) 1. 1 32 [85] Boc N 6 6 81 [81] 2. 1 43 [61] 6 97 [61] 3. 1 24 [24] 6 81 [92] 4. 1 95 [98] 1 6 42 [68] 5. 1 95 [98] 6 80 [55] 6. 1 98 [85] 6 96 [67] 7. 1 94 [95.5] 6 100 [88]
N-aryl Substituted xazolidinone for the Epoxidation of lefins 7 N X Entry Ketone yield (ee) (%) yield (ee) (%) 1. 7a 71 (83) (2R,3S) 56 (80) (R) 2. 7b 60 (84) (2R,3S) 60 (80) (R) 3. 7c 72 (90) (2R,3S) 61 (80) (R) 7a, X = p-me 7b, X = p-me 7c, X = p-mes 2 7d, X= p-n 2 7e, X = o-n 2 4. 7d 55 (90) (2R,3S) 30 (79) (R) 5. 7e 59 (78) (2R,3S) 55 (62) (R) X N X X N N Spiro 1 Favored Spiro 2 Planar 1 Shu, L.; Wang, P.; Gan, Y.; Shi, Y. rg. lett. 2003, 3, 293-296.
N-aryl Eubstituted xazolidinone for the Epoxidation of cis lefins Ketone 3a Ketone 3b Entry Substrate Conv. (ee) (%) Conv. (ee) (%) 1. 99 (84) 100 (90) N Catalyst X 2. 3. Me Me 86 (88) 80 (92) 94 (91) 100 (93) 3a, X= Me 3b, X= S 2 Me 4. 5. X X= Me 100 (88) 96 (92) X=F 99 (87) 100 (91) X=N 2 86 (98) 91 (97) Me Me 72 (92) 100 (97) 6. Me 75 (91) 97 (96) 7. Me Me Me 97 (91) 100 (94) Shu, L.; Shi, Y. Tetrahedron Lett. 2004, 45, 8115-8117.
Possible Transition State N Me Y X N Me Y X Spiro 1 Favored Spiro 2 Edge-tilted-T Shu, L.; Wang, P.; Gan, Y.; Shi, Y. Tetrahedron. lett. 2004, 3, 8115-8117.
Summary R N 6 Effective catalyst for cis and Terminal olefins R= Boc, X
ydrogen Peroxide as Primary xidant Instead of Potassium Peroxomonosulfate (KS 5 ) R 2 R 3 2 2 C 3 CN-K 2 C 3 R 2 R 3 1, catalyst R 2 R 3 R 3 R 2 1 3 C N N 4 2 C 3 C 3 CN + 2 2 N 3 C 5 3 C N 2 N 3 C 3 Shu, L.; Shi, Y. Tetrahedron, 2001, 57, 5213-5218.
Comparison Between 2 2 and KS 5 as xidant R 2 R 3 1 2 2 C 3 CN-K 2 C 3 R 2 R 3 2 2 KS 5 Entry Substrate Yield (ee) (%) Yield (ee) (%) 1. 2. 93 (92) 90 (98) 94 (96) 85 (98) 3. 94 (95) 89 (96) 4. 94 (98) 94 (98) 5. 88 (89) 98 (95) Shu, L.; Shi, Y. Tetrahedron, 2001, 57, 5213-5218
First Reported Chiral Aldehydes for the Epoxidation of lefins Entry Substrate Catalyst yield (ee) (%) Config. 2 C Bn 1 C Bn, KS 5 C 3 CN, 0 o C, 2h p 10.5 C 3 4 1. 2 16 (63.5) (R,R) 2. 3 54 (93.5) (R,R) 3. 4 31 (39) (R,R) 4. 5. 2 3 8 (81) 8 (92) (R) (R) 6. 4 4 (36) (R) 7. 2 14 (70) (R,R) 8. 2 28 (48) (R,R) 9. 3 12 (67) (R,R) 10 2 50 (18) (S) 11. 3 36 (18) (S) Bez, G.; Zhao, C. Tetrahedron Letter, 2003, 44, 7403-7406.
Transition State Analysis 2 C Bn C 3 4 Favored (R,R) Disfavored (S,S) Bez, G.; Zhao, C. Tetrahedron Letter, 2003, 44, 7403-7406.
Conclusion Advantages 1. igh catalytic activity of ketone catalyst was achieved. 2. igh level of enantioselectivity was achieved. Disadvantages 1. Broad generality of substrates couldn t be achieved.
Acknowledgement Prof. Babak Borhan Prof. W.. Reusch Prof. J. E. Jackson Prof. W. D. Wulff Chrysoula, Courtney, Dan, Jennifer, Jun, Marina, Montserrat, Stewart, Tao, Shang Vijay, Keith