中科大有机化学氧化反应总结
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OH
ee (%) 93 92 95 98 98
Using (DHQD)2PHAL as the Ligand.
Epoxides from Diols
OH
MeC(OMe)3
R' PPTS
R
OH
O R
OMe "Halogen
O
source"
O+O
HBr-AcOH, R
R' AcCl, AcBr,
X- R'
The Sharpless Epoxidation
HO
tBuOOH, VO(acac)2 HO
O
tBuOOH
tBu O RO VO HO O
slow
tBuOH
HO
tBuOOH, VO(acac)2 OR O V O O tBu O
tBu
O RO HO V O
O
Regioselectivity
Me Me
- AD-mix- contains (DHQD)2PHAL as the ligand.
- Conditions: t-BuOH, H2O (1:1), 0 oC, 6-24 h. For non-terminal olefins, the addition of MeSO2NH2 leads to faster reaction.
Mnemonic Device
DHQD-R -face
RS
RM
RL
H
-face DHQ-R
Sharpless AD of Olefins
olefin
n-Bu
Bu-n
Ph Ph
n-C5H11 Ph
CO2Et CO2Et
n-Bu
Ph Ph
n-C8H17
ligand
(DHQD)2PHAL (DHQ)2PHAL
R
R
OO
O
Os LO
R
RR
HO OH
OO
O
Os O
Organic
Aqeous
2OH- + 2H2O
HO O Os
OH
2-
HO O OH
HO O Os
O
2-
HO O O
2OH-
2OH- + 2Fe(CN)63-
2H2O + 2Fe(CN)64-
Pseudo-Enantiomeric Ligands
Et
(DHQD)2AQN 90% ee
77% ee,
88% ee
44% ee
78% ee
Regioselectivity of AD with Dienes
olefin
CO2Et CO2Et
product
yield (%)
OH
78
OH
OH
CO2Et
78
OH OH
CO2Et
93
OH
HO 73
OH
HO 70
+
OO Os
OO
Os (VIII)
OO Os
OO
H2O
OH
+
HO O Os
OH HO O
Os (VI)
Cooxidants:
O NO
K3Fe(CN)6
Sharpless Asymmetric Dihydroxylation (AD)
Using NMO as the Cooxidant
HO OH RR
OH Me
VO(acac)2, TBHP, 80 oC Regioselection 20:1
Me Me
OH Me
O
HO MeO2C
Me VO(OEt)3 (0.2 eq.), t-BuOOH (3.0 eq.)
CH2Cl2, 25 oC, 3 h, 90%;
HO MeO2C
Me O
The Sharpless Asymmetric Epoxidation
OH
RO2C
CO2R OH
R =Me, L-(+)-DMT R =Et, L-(+)-DET R =iPr, L-(+)-DIPT
Geometry and Substituents of Olefins
Bu-t
OH
TBHP, Ti(OiPr)4 (1.2 eq.),
t-Bu
(+)-DET (1.5 eq.), -20 oC
ee (%)
97 93
>99 >99
99 96
97 95
98 95
99 97
97 97
84 80
configuration
R,R S,S
R,R S,S
2S,3R 2R,3S
2S,3R 2R,3S
R S
R,R S,S
R S
R S
Ligand (DHQD)2AQN
Cl BnO
O
Ph
(DHQD)2PHAL 63% ee
D-(-) dialkyl tartrate [O]
R2 R3
R1
OH
L-(+) dialkyl tartrate [O]
tBuOOH, Ti(OiPr)4, ms, CH2Cl2, -20 oC
R2 R3
O
R1
OH
R2 R3
O
R1
OH
OH
RO2C
CO2R OH
R =Me, D-(-)-dimethyl tartrate (DMT) R =Et, D-(-)-diethyl tartrate (DET) R =iPr, D-(-)-diisopropyl tartrate (DIPT)
Me3Si C5H11-n
OH krel =700
Me Me
OH krel =20
Nucleophilic Opening of Epoxides
BnO
OH OH
LiAlH4 Et2O, 0 oC
83%
BnO
NaN3, NH4Cl, MeO(CH2)2OH
91%
OH O
(CH3)2CuLi Et2O, -40 oC
(DHQD)2PHAL (DHQ)2PHAL
(DHQD)2PHAL (DHQ)2PHAL
(DHQD)2PHAL (DHQ)2PHAL
(DHQD)2PHAL (DHQ)2PHAL
(DHQD)2PHAL (DHQ)2PHAL
(DHQD)2PHAL (DHQ)2PHAL
(DHQD)2PHAL (DHQ)2PHAL
H2O high ee
O OO R Os
O OR
R
R
OO
O
Os O
NMM
Primary cycle NMO
L
R O OO R
Secondary cycle R
Os OO
R
L
R
R
R
OO
O
Os O
R
L
low ee
L
H2O
HO OH
RR
Using K3Fe(CN)6 as the Cooxidant
LR
faster
R2 R3
O
R1
OH
RH
faster
R2 R3
O
R1
OH
HR
slower
R2 R3
O
R1
OH
HR
R2 R3
R2 R3
R2 R3
R2 R3
R2 R3
R1
O OH R1
(-)-tartrate
OH
R1
(+)-tartrate O
OH
R1
OH R1
OH
RH
HR
R
RH
HR
Me
OH krel =104
OBn OSO2CH2Cl
Kinetic Resolution of Allylic Alcohols
R2 R3
R1
OH
R
(-)-tartrate
R2 R3
R1
OH
RH
(+)-tartrate
(-)-tartrate
R2 R3
R1
OH
HR
(+)-tartrate
slower
R2 R3
O
R1
OH
RH
OH
Bu-t
O
75%, 25% ee
OH
t-Bu
O
52%, 95% ee
OH
OH t-Bu
O
42%, 85% ee
OH
t-Bu
Regioselectivity
OH Ti(OiPr)4, (+)-DET, tBuOOH
O OH
Me
Me
CH2Cl2, -25 oC, 4 h
Me
Me
94% yield, 91% ee
TMSCl,TMSBr
OAc
X
R
R' + R
R'
X
OAc
base, MeOH R
O R'
O
O 96% ee
O Ph
O Ph
O CO2Me PhO
O
97% ee
99% ee
89% ee
Me
Me
Reagent-Control
BnO BnO
TBHP, Ti(OiPr)4, (+)-DET
OH
75%
BnO BnO O
OH (single)
OBn OSO2CH2Cl
OBn OSO2CH2Cl
TBHP, Ti(OiPr)4, (-)-DET; 91%
BnO BnO O
OH (single)
Et
N
N
NN
H
O
O
H
MeO
OMe
MeO
Et Et
N
N
NN
H
O
O
H
OMe
N
N
(DHQ)2PHAL
Et N
H MeO
Ph
O百度文库
O
NN
Et N
H OMe
N
Ph
N
(DHQ)2PYR
N
N
(DHQD)2PHAL
Et
N O
H
MeO
O
Et
N
O H
O
OMe
N
N
(DHQ)2AQN
AD-mix Reagents
- 1.4 g AD-mix- will oxidize 1 mmol olefin, contains: 0.98 g K3Fe(CN)6 (3 mmol), 0.41 g K2CO3 (3 mmol), 0.0078 g (DHQ)2PHAL (0.01 mmol), 0.00074 g K2OsO2(OH)4 (0.002 mmol)
74%
BnO
OH OH
KCN, CH3OH, 23 oC; 50%
Li
OTHP
Et2O, -40 to 23 oC; 63%
BnO
OH
N3 OH
BnO
OH
CN OH
BnO
OH OH
OTHP
Dihydroxylation of Olefins
Dihydroxylation with Osmium Tetroxide
ee (%) 93 92 95 98 98
Using (DHQD)2PHAL as the Ligand.
Epoxides from Diols
OH
MeC(OMe)3
R' PPTS
R
OH
O R
OMe "Halogen
O
source"
O+O
HBr-AcOH, R
R' AcCl, AcBr,
X- R'
The Sharpless Epoxidation
HO
tBuOOH, VO(acac)2 HO
O
tBuOOH
tBu O RO VO HO O
slow
tBuOH
HO
tBuOOH, VO(acac)2 OR O V O O tBu O
tBu
O RO HO V O
O
Regioselectivity
Me Me
- AD-mix- contains (DHQD)2PHAL as the ligand.
- Conditions: t-BuOH, H2O (1:1), 0 oC, 6-24 h. For non-terminal olefins, the addition of MeSO2NH2 leads to faster reaction.
Mnemonic Device
DHQD-R -face
RS
RM
RL
H
-face DHQ-R
Sharpless AD of Olefins
olefin
n-Bu
Bu-n
Ph Ph
n-C5H11 Ph
CO2Et CO2Et
n-Bu
Ph Ph
n-C8H17
ligand
(DHQD)2PHAL (DHQ)2PHAL
R
R
OO
O
Os LO
R
RR
HO OH
OO
O
Os O
Organic
Aqeous
2OH- + 2H2O
HO O Os
OH
2-
HO O OH
HO O Os
O
2-
HO O O
2OH-
2OH- + 2Fe(CN)63-
2H2O + 2Fe(CN)64-
Pseudo-Enantiomeric Ligands
Et
(DHQD)2AQN 90% ee
77% ee,
88% ee
44% ee
78% ee
Regioselectivity of AD with Dienes
olefin
CO2Et CO2Et
product
yield (%)
OH
78
OH
OH
CO2Et
78
OH OH
CO2Et
93
OH
HO 73
OH
HO 70
+
OO Os
OO
Os (VIII)
OO Os
OO
H2O
OH
+
HO O Os
OH HO O
Os (VI)
Cooxidants:
O NO
K3Fe(CN)6
Sharpless Asymmetric Dihydroxylation (AD)
Using NMO as the Cooxidant
HO OH RR
OH Me
VO(acac)2, TBHP, 80 oC Regioselection 20:1
Me Me
OH Me
O
HO MeO2C
Me VO(OEt)3 (0.2 eq.), t-BuOOH (3.0 eq.)
CH2Cl2, 25 oC, 3 h, 90%;
HO MeO2C
Me O
The Sharpless Asymmetric Epoxidation
OH
RO2C
CO2R OH
R =Me, L-(+)-DMT R =Et, L-(+)-DET R =iPr, L-(+)-DIPT
Geometry and Substituents of Olefins
Bu-t
OH
TBHP, Ti(OiPr)4 (1.2 eq.),
t-Bu
(+)-DET (1.5 eq.), -20 oC
ee (%)
97 93
>99 >99
99 96
97 95
98 95
99 97
97 97
84 80
configuration
R,R S,S
R,R S,S
2S,3R 2R,3S
2S,3R 2R,3S
R S
R,R S,S
R S
R S
Ligand (DHQD)2AQN
Cl BnO
O
Ph
(DHQD)2PHAL 63% ee
D-(-) dialkyl tartrate [O]
R2 R3
R1
OH
L-(+) dialkyl tartrate [O]
tBuOOH, Ti(OiPr)4, ms, CH2Cl2, -20 oC
R2 R3
O
R1
OH
R2 R3
O
R1
OH
OH
RO2C
CO2R OH
R =Me, D-(-)-dimethyl tartrate (DMT) R =Et, D-(-)-diethyl tartrate (DET) R =iPr, D-(-)-diisopropyl tartrate (DIPT)
Me3Si C5H11-n
OH krel =700
Me Me
OH krel =20
Nucleophilic Opening of Epoxides
BnO
OH OH
LiAlH4 Et2O, 0 oC
83%
BnO
NaN3, NH4Cl, MeO(CH2)2OH
91%
OH O
(CH3)2CuLi Et2O, -40 oC
(DHQD)2PHAL (DHQ)2PHAL
(DHQD)2PHAL (DHQ)2PHAL
(DHQD)2PHAL (DHQ)2PHAL
(DHQD)2PHAL (DHQ)2PHAL
(DHQD)2PHAL (DHQ)2PHAL
(DHQD)2PHAL (DHQ)2PHAL
(DHQD)2PHAL (DHQ)2PHAL
H2O high ee
O OO R Os
O OR
R
R
OO
O
Os O
NMM
Primary cycle NMO
L
R O OO R
Secondary cycle R
Os OO
R
L
R
R
R
OO
O
Os O
R
L
low ee
L
H2O
HO OH
RR
Using K3Fe(CN)6 as the Cooxidant
LR
faster
R2 R3
O
R1
OH
RH
faster
R2 R3
O
R1
OH
HR
slower
R2 R3
O
R1
OH
HR
R2 R3
R2 R3
R2 R3
R2 R3
R2 R3
R1
O OH R1
(-)-tartrate
OH
R1
(+)-tartrate O
OH
R1
OH R1
OH
RH
HR
R
RH
HR
Me
OH krel =104
OBn OSO2CH2Cl
Kinetic Resolution of Allylic Alcohols
R2 R3
R1
OH
R
(-)-tartrate
R2 R3
R1
OH
RH
(+)-tartrate
(-)-tartrate
R2 R3
R1
OH
HR
(+)-tartrate
slower
R2 R3
O
R1
OH
RH
OH
Bu-t
O
75%, 25% ee
OH
t-Bu
O
52%, 95% ee
OH
OH t-Bu
O
42%, 85% ee
OH
t-Bu
Regioselectivity
OH Ti(OiPr)4, (+)-DET, tBuOOH
O OH
Me
Me
CH2Cl2, -25 oC, 4 h
Me
Me
94% yield, 91% ee
TMSCl,TMSBr
OAc
X
R
R' + R
R'
X
OAc
base, MeOH R
O R'
O
O 96% ee
O Ph
O Ph
O CO2Me PhO
O
97% ee
99% ee
89% ee
Me
Me
Reagent-Control
BnO BnO
TBHP, Ti(OiPr)4, (+)-DET
OH
75%
BnO BnO O
OH (single)
OBn OSO2CH2Cl
OBn OSO2CH2Cl
TBHP, Ti(OiPr)4, (-)-DET; 91%
BnO BnO O
OH (single)
Et
N
N
NN
H
O
O
H
MeO
OMe
MeO
Et Et
N
N
NN
H
O
O
H
OMe
N
N
(DHQ)2PHAL
Et N
H MeO
Ph
O百度文库
O
NN
Et N
H OMe
N
Ph
N
(DHQ)2PYR
N
N
(DHQD)2PHAL
Et
N O
H
MeO
O
Et
N
O H
O
OMe
N
N
(DHQ)2AQN
AD-mix Reagents
- 1.4 g AD-mix- will oxidize 1 mmol olefin, contains: 0.98 g K3Fe(CN)6 (3 mmol), 0.41 g K2CO3 (3 mmol), 0.0078 g (DHQ)2PHAL (0.01 mmol), 0.00074 g K2OsO2(OH)4 (0.002 mmol)
74%
BnO
OH OH
KCN, CH3OH, 23 oC; 50%
Li
OTHP
Et2O, -40 to 23 oC; 63%
BnO
OH
N3 OH
BnO
OH
CN OH
BnO
OH OH
OTHP
Dihydroxylation of Olefins
Dihydroxylation with Osmium Tetroxide