the use of chiral ketones /aldehydes in the asymmetric ... · the use of chiral ketones /aldehydes...
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The use of Chiral Ketones /Aldehydes in theAsymmetric Epoxidation of Olefins
Somnath Bhattacharjee Michigan State University
12th January, 2005
Introduction
Sharpless Asymmetric Epoxidation
Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.; Masamune, H.; 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.
CH2OH
(-)-diethyl tartrate
Ti(O-i-Pr)4, tBuOOHO
(2R, 3R)
O
(2S, 3S)
(+)-diethyl tartrate
Ti(O-i-Pr)4, tBuOOH
H3C
H3C
H3C
58% yield, 95% ee
70% yield, 92% ee
OH
OH
Jacobsen Asymmetric Epoxidation
Chang, S.; Lee, N. H.; Jacobsen, E. N. J. Org. Chem. 1993, 58, 6939.
N N
O OMn
HH
C2H5O2C Catalyst, 3 mol %
NaOCl
C2H5O2C
O81% yield, 87% ee.
PF6-
+
Dioxirane Catalyzed Epoxidation
O
R1 R2
HSO5
R1 R2
HO OOSO3
OH
R1 R2
O OOSO3
R1 R2
OOR2 R4
R3R1
R2 R4
R3R1 O
SO42
1
2
3
4
Curci, R.; Fiorentino, M.; Troisi, L.; Edwards, J. O.; Pater, R. H. J. Org. Chem. 1980, 45, 4758.
Schulz, M.; Liebsch, S.; Kluge, R.; Adam, W. J. Org. Chem. 1997, 62, 188.
OKHSO5Bu4NHSO4
+CH2Cl2-H2O
+O
Activities of Various ketones in Catalyzing insitu Epoxidation of trans-Stilbene
Ph
Ph CatalystOxone/NaHCO3
CH3CN/H2Ort, pH 7-7.5
Ph
Ph O
catalystR1 R2
O
1
Yang, D.; Yip, Y. C.; Tang, M. W.; Wong, M.; Zheng, J.; Cheung, K. J. Am. Chem. Soc. 1996, 118, 491-492.
Entry R1 R2reaction time (min)
1. CH3 CH3 300
2. CH3 CF3 < 4
3. CH3 CH2F 20
4. Ph CF3 70
Catalyst
First Example of Ketone-Catalyzed AsymmetricEpoxidation
CatalystOxone/NaHCO3
CH3CN/H2Ort, pH 7-7.5
O
Ph Ph
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.
Catalyst
OO
OO
F3C OCH3
1 2
3 4
MeH
Ph
CF3
OEntry ketone yield ee config. (equiv) (%) (%)
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)
Chiral Ketones with C2 Symmetry for Asymmetric Epoxidation
Asymmetric Epoxidation of UnfunctionalizedOlefins Catalyzed by Ketone
Yang, D.; Yip, Y. C.; Tang, M. W.; Wong, M. K.; Zeng, J. H.; Cheung, K. K. J. Am. Chem. Soc.1996, 118, 491-492.
OO O
O
O
1
O
PhPhPh
O
Ph
Ph
O
PhPh
47% ee(-)-(S,S) 87% ee
(-)-(S,S)
50% ee(+)-(S)
The Spiro and Planar Transition States for theDioxirane Epoxidation of Olefins
Wang, Z.; Tu, Y.; Frohn, M.; Zhang, J.; Shi, Y. J. Am. Chem. Soc. 1997,119, 11224-11235.
OO R'
ROO R'
R
OO
R'R
* orbitalOlefin
Oxygen non-bonding orbital
Spiro T.S
* orbitalOlefin
Oxygen non-bonding orbital
Planar T.S
OO
R'R
π π
Proposed Spiro Transition State for theepoxidation of trans olefins
Spiro 1Favored
Spiro 2disfavored
Yang, D.; Wong, M.; Yip, Y.; Wang, X. Tang, M.; Zheng, J.; Cheung, K. J. Am. Chem. Soc. 1998, 120, 5943-5952.
A
O HPh
PhH(S, S)
B
O PhH
HPh
(R, R)
Proposed Planar Transition State for theepoxidation of trans olefins
Planar 1favored
Planar 2disfavored
Yang, D.; Wong, M.; Yip, Y.; Wang, X. Tang, M.; Zheng, J.; Cheung, K. J. Am. Chem. Soc. 1998, 120, 5943-5952.
B
O PhH
HPh
(R, R)
A
O HPh
PhH(S, S)
Asymmetric Epoxidation of UnfunctionalizedOlefins Catalyzed by Ketones
Yang, D.; Wang, X.; Wong, M., Yip, Y.; Tang, M. J. Am. Chem. Soc. 1996, 118, 11311-11312.
A
O HPh
PhH(S, S)
CatalystOxone/NaHCO3
CH3CN/H2Ort, pH 7-7.5
PhPh O
O O
O
OX
X
3
3'(R)-1
1. X= H2. X= Cl
3. X= Br
4. X= I5. X= CH2OCH3
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)
New Approaches for Asymmetric Epoxidation oftrans Olefin
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.
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
Ph Ph O
10 mole % (S)-6
Oxone, K2CO3 DME-H2O C
OO
O FF
1 Song 2 Denmark
O
Hypothetical Transition Structures for Approachof Alkenes to Dioxirane of (-)-2
Denmark, S. E.; Matsuhashi, H. J. Org. Chem. 2002, 67, 3479-3486.
Me Me
F
O
O F
RR'
R'R b
a
Behar’s Approach to Improve theEnantioselectivity for Asymmetric Epoxidation
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
O
R2R1
R4R3
O FF
3 Denmark
4. R1, R2, R3, R4 = H5. R1, R3, R4 = H, R2 = F 6. R1, R3 = H, R2, R4 = F 7. R1, R2, R3 = F, R4 = H 8. R1, R2, R3, R4 = F
Behar
Stearman, J. C.; Behar, V. Tetrahedron. Lett. 2002, 43, 1943-1946.
Summary
OO
1 Song
O FF
2 Denmark
O
FR1
FR3
Behar
OO O
O
OCl
Cl
3
3'(R)-3
O
Fructose-derived Chiral Ketones for Epoxidation
Fructose-derived Ketone Catalyst for theAsymmetric Epoxidation of trans Stilbene
Wang, Z.; Tu, Y.; Frohn, M.; Zhang, J.; Shi, Y. J. Am. Chem. Soc. 1997,119, 11224-11235.
O
O
OO
OO
Oxone, H2O-CH3CN pH 7-7.5
1
dPh
Ph
PhPhO
entry Time (h) Isolated Yield (%) ee (%)
1. 1 31 > 95
2. 2 39 > 95
3. 3 40 89
4. 4 47 85
Possible Reaction Pathway of Ketone 1
Wang, Z.; Tu, Y.; Frohn, M.; Zhang, J.; Shi, Y. J. Am. Chem. Soc. 1997,119, 11224-11235.
R1R2
R3O
HSO5O
O
OO
OOR1
R2
R3
O OO
OO
OO
O OO
OO
OOH
O SO3
OH
O
OOO
OO
OSO4
OO
OO
OO
O
O OO
OO
OO
O SO3
1
4
2
2
3
+
5 6Hydrolysis
O
Baeyer-Villiger Reaction
Baeyer-Villiger Reaction
Renz, M.; Meunier, B.; Eur. J. Org. Chem. 1999, 737Crudden, C. M.; Chen, A. C.; Calhoun, L. A.Angew. Chem., Int. Ed. 2000, 39, 2852
R R'
O H2O2
R O
OR'
O H
R O OH
R'
H OH2
OH2
R R'
OH
H O O H
Mechanism
R O
OR'
Example
F
H2O2 O
OF
O
O
F+
71% 29% F
O
E
G
Effect of pH in Ketone Catalyzed Epoxidation
Frohn, M.; Wang, Z.; Shi, Y. J. Org. Chem. 1998, 63, 6425-6426.
O
O
OO
OO
Catalyst 1
R1R2
R3O
HSO5O
O
OO
OOR1
R2
R3
O OO
OO
OO
O OO
OO
OOH
O SO3
OH
O
OOO
OO
OSO4
OO
OO
OO
O
O OO
OO
OO
O SO3
1
4
2
2
3
+
5 6Hydrolysis
O
Baeyer-Villiger Reaction
entry Time (h) Yield (ee) (%) Yield (ee)(%)
1. 4 47 (85) 86 (>95)
pH 7-7.5 pH 10.5-11.5
Oxone, H2O-CH3CN pH 7-7.5
PhPh
PhPhO
Approaches to Circumvent Baeyer-VilligerReaction
O
O
OO
OO
O
O
O
OO
AcOAcO
4 5
O
O
OO
OO
OO
OO
OO
OO
OOO
OO
O+
2
42 mCPBA
1 3major
Wu, X.; She, X.; Shi, Y. J. Am. Chem. Soc. 2002, 124, 8792-8793.
PhCO2Et
PhCO2EtEt
CO2Et
CO2Et
CO2Et
Ph
CO2EtPh
Entry Substrate Yield (%) ee (%) config.
1.
2.
73 96 (+)-(2S,3R)
3.
91 93 (+)
64 82 (+)
4.
77 89 (+)
5.96 94 (+)
6. 84 44 (-)-(2S,3S)
Epoxidation by catalyst 5
Comparison Between Ketones 1 and 5O
O
OO
OO
O
O
OO
AcOAcO
1 5
Tian, H.; She, X.; Shi, Y. Organic Lett. 2001, 3, 715-718
Entry Substrate Yield (ee) (%) Yield (ee) (%) config.
1.
2.
(R, R)
3.
67 (96) (R, R)
73 (94) (R, R)
4. 80 (93) (R, R)
5.
Ph
Ph
Ph
PhMe
Ph
Ketone 1 Ketone 5
94 (95.5)
85 (97.9)
87 (94)
89 (95.5)
94 (98)
81 (83)
93 (92) (R, R)
OTBS
PhPh
Transition State Analysis for the Epoxidation oftrans Olefin by Ketone 1
Tu, Y.; Wang, Z.' Shi, Y. J. Am. Chem. Soc. 1996, 118, 9806-9807.
O
Ph HH Ph
O
O OOO
OO
O
O OOO
OOO
O OOO
OO
O
O
OO
Spiro 1Favored
Planar 1disfavored
Planar 2 Favored
Spiro 2disfavored
OO
Ph
PhPh
(R, R)
PhH
Ph H(S, S)
Ph
Ph
PhPh
1
2
Ph
O
CatalystOxone/NaHCO3
CH3CN/H2O rt
O PhH
HPh
(R, R)Ph
Ph
Asymmetric Epoxidation of Trisubstituted Olefinby Ketone 1
O
O
OO
OO
1 (catalyst)
Wang, Z.; Tu, Y.; Frohn, M.; Zhang, J.; Shi, Y. J. Am. Chem. Soc. 1997, 119, 11224-11235.
R3 R1
R3 R1
O Oxone, H2O-CH3CN
R2R2pH 11, catalyst
Entry Substrate Yield (%) ee (%) Config.
1.
2.
3.
89 96.8 (R,R)
93 76.4 (+)-(R)
89 95.5 (+)-(R,R)
Ph
PhPh
Ph
Transition State Analysis for the Epoxidation ofTrisubstituted Olefins
R3 R1
R3 R1
O Oxone, H2O-CH3CN
R2R2pH 11, catalyst
O
O
OO
OO
1 (catalyst)
Wang, Z.; Tu, Y.; Frohn, M.; Zhang, J.; Shi, Y. J. Am. Chem. Soc. 1997, 119, 11224-11235.
O
R3 R2H R1
O
O O OO
OO
O
O OOO
OO O
O O OO
OO R2R1
R3
O
O
OO
Spiro 1Favored
Planar 1disfavored
Planar 2disfavoredSpiro 2
disfavored
Major
OO
R1R2
R3
R2R1
R3R2R1R3
1
Transition State Analysis for the Epoxidation ofTrisubstituted Olefin by Ketone 1
O
O
OO
OO1 (catalyst)
Wang, Z.; Tu, Y.; Frohn, M.; Zhang, J.; Shi, Y. J. Am. Chem. Soc. 1997, 119, 11224-11235.
R3 R1
R3 R1
O Oxone, H2O-CH3CN
R2R2pH 11, catalyst O
O OOO
OO
O
O O OO
OO
Spiro 4disfavored
O
O O OO
OO R3R2R1
O
O O OO
OO R1R3 R2
O
H R1R3 R2
Spiro 3disfavored Planar 3
disfavored
Planar 4Favored
minor
R1R2
R3
R2R1R3
Effects of the Size of Substituents onEnantioslectivity
Wang, Z.; Tu, Y.; Frohn, M.; Zhang, J.; Shi, Y. J. Am. Chem. Soc. 1997, 119, 11224-11235.
C10H21
26% ee 79% ee 81% ee
Effect of the size of R1
ee increases as the size of R1 decreases
Effect of the size of R3
86.5% ee 91% ee
ee increases as the size of R3 increase
O
O O OO
OOR3R1 R2 O
R3 R2H R1
Spiro 1
Major
O
O O OO
OO R1R3 R2
O
H R1R3 R2
Planar 4
minor
Epoxidation of cis and Terminal Olefins byKetone 1
Wang, Z.; Tu, Y.; Frohn, M.; Zhang, J.; Shi, Y. J. Am. Chem. Soc. 1997,119, 11224-11235.
O
O
OO
OO
1 (catalyst)
O
O
Ph
C8H17
Entry Subtrate Yield (%) ee (%) Config.
1.
2.
3.
4.
92 12 (-)-(1S,2R)
43 61.4 (+)-(R,R)
90 24.3 (+)-(R)
92 17 (+)-(R)
Ph5. 95 19.6 (-)-(S)
Transition State Analysis for cis and TerminalOlefins
Wang, Z.; Tu, Y.; Frohn, M.; Zhang, J.; Shi, Y. J. Am. Chem. Soc. 1997, 119, 11224-11235.
OOO
O OOO
R2R3
OOO
O OOO
R3R2
spiro 1
spiro 2
cis Olefin
O
O O OO
OO
Spiro 3
O
O O OO
OO
Spiro 4
R1
O
O
OO
Planar 3
OO
O
O O OO
OO
Planar 4
R1
R1
R1O
R1
H
O
H
R1
1
2
Terminal Olefins
Summary
O
O
OO
OO
O
O
OO
AcOAcO
1
5
Advantages: Enantioselctivity is high for trans and tri substitued olefins.
Disadvantages: Enantioselectivity is very low for cis and terminal olefins.
Effective catalyst for elctron deficient olefins.
Transition State Analysis to Design newCatalyst for cis Olefins
Tian, H.; She, X.; Shu, L.; Yu, H.; Shi, Y. J. Am. Chem. Soc. 2000, 122, 11551-11552.
O
OO
XO MePh
Y
O
OO
XO PhMe
Y
Spiro 3 Spiro 4
O
OO
OO MePhO
OO
OO PhMe
Spiro 1 Spiro 2
Fructose-derive new Catalyst for theEpoxidation of cis Olefins
O
O
OO
NO
O
Boc
6
Tian, H.; She, X.; Yu, H.; Shu, L.; Shi, Y. J. Org. Chem. 2002, 67, 2435-2446
Ph
O
O
Entry Substrate Yield (%) ee (%) Config.
1. 87 91 (-)-(1R,2S)
2. 91 92 (-)-(1R,2S)
3. 77 91 (-)-(5R,6S)
4. 82 91 (-)-(2S,3R)
5. 61 97 (+)
6, Oxone
Up to 97% ee
R1 R1
O
Transition State Analysis for the Epoxidation ofcis Olefins
Tian, H.; She, X.; Yu, H.; Shu, L.; Shi, Y. J. Org. Chem. 2002, 67, 2435-2446
O
O OOO
NBocO
O
O OOO
NBocO RArO
O OOO
NBocO ArR
Spiro 1 Spiro 2
Planar 1
O
O OOO
NBocO
Planar 2
R Ar Ar R
Catalyst 6 for the Epoxidation of TerminalOlefins
R 6, OxoneUp to 85 % ee
R O
O
O
OO
NO
O
Boc
6
Tian, H.; She, X.; Shi, Y. Org. lett. 2001, 5, 1929-1931.
Entry Substrate Yield (%) ee (%) Config.
1.100 81 (-)-(R)
2. 86 84 (-)-(R)
3. 93 71 (-)
O
O OOO
NBocOO
O OOO
NBocO
O
O OOO
NBocO
Spiro 1 Spiro 2 Planar 1
H PhPh
H PhH
Comparison Between Ketone Catalysts 1 and 6
O
O
OO
NO
O
Boc6
O
O
OO
OO 1
O
O
Ph
6
6
Ph
6
PhPh
6
Substrate ketoneEntry
1. 1 32 [85]
Yield (ee) (%)
6
2.
81 [81]
1 43 [61]
6 97 [61]
3. 1 24 [24]
81 [92]
4. 1 95 [98]
42 [68]
5. 1 95 [98]
80 [55]
6. 1 98 [85]
6 96 [67]7. 1 94 [95.5]
100 [88]Ph
N-aryl Substituted Oxazolidinone for theEpoxidation of Olefins
O
OO
NO
O
OX
7
7a, X = p-OMe7b, X = p-Me7c, X = p-MeSO27d, X= p-NO27e, X = o-NO2
Shu, L.; Wang, P.; Gan, Y.; Shi, Y. Org. lett. 2003, 3, 293-296.
Ph PhEntry 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)
4. 7d 55 (90) (2R,3S) 30 (79) (R)
5. 7e 59 (78) (2R,3S) 55 (62) (R)
OO O
NO
OO
O
OO O
NO
OO
O
OO O
NO
OO
O
H
Spiro 1Favored Spiro 2 Planar 1
XPh
HH
Ph
X XPh
N-aryl Eubstituted Oxazolidinone for theEpoxidation of cis Olefins
O NO
OOO
X
Catalyst
Entry Substrate Conv. (ee) (%) Conv. (ee) (%) Ketone 3a Ketone 3b
1. 99 (84) 100 (90)
Me
Me
X
2.
3.
4.
86 (88) 80 (92)
94 (91) 100 (93)
X= Me 100 (88) 96 (92)
X=F 99 (87) 100 (91)X=NO2 86 (98) 91 (97)
5.Me
Me 72 (92) 100 (97)
Me
MeMe
Me97 (91) 100 (94)
75 (91) 97 (96)6.
7.
3a, X= Me3b, X= SO2Me
Shu, L.; Shi, Y. Tetrahedron Lett. 2004, 45, 8115-8117.
Possible Transition State
Shu, L.; Wang, P.; Gan, Y.; Shi, Y. Tetrahedron. lett. 2004, 3, 8115-8117.
H H
HH
Edge-tilted-T
O
O O
NO
OO
O
Spiro 1Favored Spiro 2
Y
MeX
O
O O
NO
OO
OX
Me Y
Summary
O
O
OO
NO
O
R
6
R= Boc, X
Effective catalyst for cis and Terminal olefins
Hydrogen Peroxide as Primary Oxidant Insteadof Potassium Peroxomonosulfate (KHSO5)
R1
R2
R3
H2O2CH3CN-K2CO3 R1
R2
R3O
O
O
OO
OO1, catalyst
H2O2CH3CN H3C OOH
NH+
5
Shu, L.; Shi, Y. Tetrahedron, 2001, 57, 5213-5218.
R1R2
R3O
O
O
OO
OOR1
R2
R3
O OO
OO
OO
O OO
OO
OO
O
H
CH3
N H
H3C
O
NH2
H3C OOH
NH
O OO
OO
OOH
OCH3
NH
1
4 2
3
Comparison Between H2O2 and KHSO5 asOxidant
R1
R2
R3
O
O
OO
OO
H2O2CH3CN-K2CO3
R1
R2
R3O1 H2O2
Ph
PhPh
PhPh
Ph
Ph
KHSO5
Entry Substrate Yield (ee) (%) Yield (ee) (%)
1. 93 (92) 94 (96)
90 (98) 85 (98)
94 (95) 89 (96)
94 (98) 94 (98)
98 (95)88 (89)
2.
3.
4.
5.
Shu, L.; Shi, Y. Tetrahedron, 2001, 57, 5213-5218
First Reported Chiral Aldehydes for theEpoxidation of Olefins
PhPh
CHOOBn , KHSO5
PhPhO
CH3CN, 0 oC, 2h pH 10.5
1
O OO
OO
CHOOBn
O OO
OO
CHOOH
O
OO
O O
O
OH
3 42
Bez, G.; Zhao, C. Tetrahedron Letter, 2003, 44, 7403-7406.
PhPh
PhPhPh
Ph
Ph
(R)
(R)
(R)
(S)
(S)
Entry Substrate Catalyst yield (ee) (%) Config.
1. 2 16 (63.5) (R,R)
3 54 (93.5) (R,R)
4 31 (39) (R,R)
2.
3.
4. 2 8 (81)
3 8 (92)
4 4 (36)
5.
6.
7. 2 14 (70) (R,R)
8. 2 28 (48) (R,R)
3 12 (67) (R,R)9.
10 2 50 (18)
11. 3 36 (18)
OH
Ph
Transition State Analysis
O OO
OO
CHOOBn
O OO
OO
CHOOH
O
OO
O O
O
OH
3 42
O O
OO
OOO
H
HPh
Ph
O O
OO
OOO
H
H
PhPh
PhH
HPh
O
HPh
PhH
O
(R,R)Favored
(S,S)
Disfavored
Bez, G.; Zhao, C. Tetrahedron Letter, 2003, 44, 7403-7406.
Conclusion
Advantages1. High catalytic activity of ketone catalyst was achieved.2. High level of enantioselectivity was achieved.
Disadvantages1. Broad generality of substrates couldn’t be achieved.
Acknowledgement
• Prof. Babak Borhan• Prof. W. H. Reusch• Prof. J. E. Jackson• Prof. W. D. Wulff• Chrysoula, Courtney, Dan, Jennifer, Jun, Marina,
Montserrat, Stewart, Tao, Shang• Vijay, Keith