哈佛大学有机化学课件Lecture10extra
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Me
Me
Me
O
O Me
O
Me Et O
O HO
5 OH
n-C12H25
LnM
(Z,Z,Z)-premonensin triene
(E,E,E)-pregoniocin triene
Me Me Et
Me
AD-mix β
Me Me
HO OH Et
Me
H O
Et2Zn, Ti(O-i-Pr)4
NHSO2CF3
[2+2]
HOAc
H RL RS O RZ H RE OH
reductive elimination
H O
RE O
19% combined, 3.7:1 (trans:cis)
Me Me O O H Me O
H RL RS
Cr O
RZ OH
24%, 17:1
trans-substituted tetrahydrofuran
n-C12H25
NHSO2CF3
CrO3(py)2
Me Me HO H O Et O
Me
1) Ac2O, Et3N cat. DMAP 2) NaBH4, CeCl3
Et
*
OH
(Cl2CHCO2)ReO3
n-C12H25
(Cl2CHCO)2O
Me Me AcO H O Et Me Me AcO H OH
C. A. Morales
Olefin Addition Rxns in Polyether Synthesis-1 An alternate biosynthetic proposal:
OH Me OH HO2C H Me Me
O
Chem 206
One plausible biosynthetic proposal for polyether natural products:
Me Me OH Me Me Me Me Me O O H Me H Me Me OH Me Me Me O H Me O H OH
PCC HOAc
i-Pr Me O H O Me
Me
PCC HOAc
...simple oxidation occurs more rapidly than oxidative cyclization.
Me R O O Me Me Me
Me
Me Me
O Me
O
LnM
Et
O
Me OH
[O]
(Z,Z,Z)-premonensin triene
[2+2]
OH Me OH Me
O
Me Me
Me R O O
Me O
Me O
Me
HO2C H Me Me
Me O
M
O
Et
O
O
Me OH
HO2C Me OH
OH
reductive elimination
High syn-stereospecificity for tertiary alcohols
McDonald, F. E. JACS, 1994, 116, 7921.
C. A. Morales
Olefin Addition Rxns in Polyether Synthesis-3
Chem 206
Me
(Cl2CHCO2)ReO3 (Cl2CHCO)2O
Et Me H OH H
*
H
O
H O
OH H H n-C12H25
O
H
One stereocenter ( ) * controls the induction of six additional centers.
C
O Et H
D
O
Me HO Me MeO H HO2C Me Me Me Me Me OH H H O OH O O HO
from lecture 7
Cane, D. E. JACS, 1983, 105, 3394. Cane, D. E. JACS, 1982, 104, 7274.
Monensin
Townsend, C. A.; Basak, A. Tetrahedron, 1991, 47, 2591.
C. A. Morales
5H
H O
O
H O
OH H H n-C12H25
C
O O Me H O Et H
D
O
H
Goniocin
McDonald, F. E. Pure App. Chem., 1998, 70, 355.
Monensin
38%, 9.9:1
Me Me OH
Me
源自文库
Me Me
Me Me O H Me Me O H
Me Me OH Me Me O O H Me H OH
PCC
Me
Does this explain the lower degree of "trans-cross-ring" selectivity observed for (E)-olefins?
Application of the model for syn-oxidative polycyclization using an all (Z)-polyolefin:
OH Me OH HO2C H Me Me
O
Application of the model for syn-oxidative polycyclization on an all (E)-polyolefin:
Me Me Me Me
O LnM
HO Me MeO H HO2C Me Me O O Me H O
Me
H
O
O Et O
Me
Me OH
Me
Me
Me H
O
O H H OH HO Me Me Me OH O H HO2C Me Me O Me H O Et H O O H H OH
Monensin B
Me MeO
9% combined, 11:1 (trans:cis)
Me Me O H Me O O
Conformational model for syn-oxidative cyclization:
H H RL O RS RZ RE H Cr O O OH H RL RS H O H RE Cr O O OH RZ
Olefin Addition Rxns in Polyether Synthesis-2
But for secondary alcohols...
i-Pr Me OH Me Me
Chem 206
A biomimetic model for syn-oxidative polycyclization:
Me
Me
O
O Me
O
Me Et O
O HO
5 OH
n-C12H25
LnM
(Z,Z,Z)-premonensin triene
(E,E,E)-pregoniocin triene
Me Me Et
Me
AD-mix β
Me Me
HO OH Et
Me
H O
Et2Zn, Ti(O-i-Pr)4
NHSO2CF3
[2+2]
HOAc
H RL RS O RZ H RE OH
reductive elimination
H O
RE O
19% combined, 3.7:1 (trans:cis)
Me Me O O H Me O
H RL RS
Cr O
RZ OH
24%, 17:1
trans-substituted tetrahydrofuran
n-C12H25
NHSO2CF3
CrO3(py)2
Me Me HO H O Et O
Me
1) Ac2O, Et3N cat. DMAP 2) NaBH4, CeCl3
Et
*
OH
(Cl2CHCO2)ReO3
n-C12H25
(Cl2CHCO)2O
Me Me AcO H O Et Me Me AcO H OH
C. A. Morales
Olefin Addition Rxns in Polyether Synthesis-1 An alternate biosynthetic proposal:
OH Me OH HO2C H Me Me
O
Chem 206
One plausible biosynthetic proposal for polyether natural products:
Me Me OH Me Me Me Me Me O O H Me H Me Me OH Me Me Me O H Me O H OH
PCC HOAc
i-Pr Me O H O Me
Me
PCC HOAc
...simple oxidation occurs more rapidly than oxidative cyclization.
Me R O O Me Me Me
Me
Me Me
O Me
O
LnM
Et
O
Me OH
[O]
(Z,Z,Z)-premonensin triene
[2+2]
OH Me OH Me
O
Me Me
Me R O O
Me O
Me O
Me
HO2C H Me Me
Me O
M
O
Et
O
O
Me OH
HO2C Me OH
OH
reductive elimination
High syn-stereospecificity for tertiary alcohols
McDonald, F. E. JACS, 1994, 116, 7921.
C. A. Morales
Olefin Addition Rxns in Polyether Synthesis-3
Chem 206
Me
(Cl2CHCO2)ReO3 (Cl2CHCO)2O
Et Me H OH H
*
H
O
H O
OH H H n-C12H25
O
H
One stereocenter ( ) * controls the induction of six additional centers.
C
O Et H
D
O
Me HO Me MeO H HO2C Me Me Me Me Me OH H H O OH O O HO
from lecture 7
Cane, D. E. JACS, 1983, 105, 3394. Cane, D. E. JACS, 1982, 104, 7274.
Monensin
Townsend, C. A.; Basak, A. Tetrahedron, 1991, 47, 2591.
C. A. Morales
5H
H O
O
H O
OH H H n-C12H25
C
O O Me H O Et H
D
O
H
Goniocin
McDonald, F. E. Pure App. Chem., 1998, 70, 355.
Monensin
38%, 9.9:1
Me Me OH
Me
源自文库
Me Me
Me Me O H Me Me O H
Me Me OH Me Me O O H Me H OH
PCC
Me
Does this explain the lower degree of "trans-cross-ring" selectivity observed for (E)-olefins?
Application of the model for syn-oxidative polycyclization using an all (Z)-polyolefin:
OH Me OH HO2C H Me Me
O
Application of the model for syn-oxidative polycyclization on an all (E)-polyolefin:
Me Me Me Me
O LnM
HO Me MeO H HO2C Me Me O O Me H O
Me
H
O
O Et O
Me
Me OH
Me
Me
Me H
O
O H H OH HO Me Me Me OH O H HO2C Me Me O Me H O Et H O O H H OH
Monensin B
Me MeO
9% combined, 11:1 (trans:cis)
Me Me O H Me O O
Conformational model for syn-oxidative cyclization:
H H RL O RS RZ RE H Cr O O OH H RL RS H O H RE Cr O O OH RZ
Olefin Addition Rxns in Polyether Synthesis-2
But for secondary alcohols...
i-Pr Me OH Me Me
Chem 206
A biomimetic model for syn-oxidative polycyclization: