BURIED TREASURES CASCADES WE HAVEN'T SEEN · oh h o buried treasures: cascades we haven't seen n o...
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OH H O BURIED TREASURES: CASCADES WE HAVEN'T SEEN N O O O O OH HO H O H O MeNH 2 R. Robinson, J. Chem. Soc., 1917, 762 O O Me H Me H H H Ph H H H H H CO 2 Me H O H CH 3 O H 3 C H 3 C H HO H H H H H CH 3
Transcript of BURIED TREASURES CASCADES WE HAVEN'T SEEN · oh h o buried treasures: cascades we haven't seen n o...
OH
H
O
BURIED TREASURES: CASCADES WE HAVEN'T SEEN
N
O
OO
O
OH
HO
HO
H O
MeNH2
R. Robinson,J. Chem. Soc., 1917, 762
O
O
Me H
Me
H H
H
PhH
HH
H
HCO2MeH
O
H
CH3
O
H3C
H3CH
HOH
H
H
H
H
CH3
Cascades ArticulatedMain Entry: 1cas·cade Pronunciation: (")kas-'kAd Function: noun Etymology: French, from Italian cascata, from cascare to fall, from (assumed) Vulgar Latin casicare, from Latin casus fall, Date: 1641
1: a steep usually small fall of water; especially :one of a series
2a : something arranged or occurring in a series or in a succession of stages so that each stage derives from or acts upon the product of the preceding <blood clotting involves a biochemical cascade > b: a fall of material (as lace) that hangs in a zigzag line
3: something falling or rushing forth in quantity <a cascade of sound> <a cascade of events>
4: One-pot, sequential reactions involving more than one intermediate, preferrably 1) leading to an increase in molecular complexity and 2) without changing reaction conditions
see: Chem. Commun., 2003, 551
Cascades ArticulatedMain Entry: 1cas·cade Pronunciation: (")kas-'kAd Function: noun Etymology: French, from Italian cascata, from cascare to fall, from (assumed) Vulgar Latin casicare, from Latin casus fall, Date: 1641
1: a steep usually small fall of water; especially :one of a series
2a : something arranged or occurring in a series or in a succession of stages so that each stage derives from or acts upon the product of the preceding <blood clotting involves a biochemical cascade > b: a fall of material (as lace) that hangs in a zigzag line
3: something falling or rushing forth in quantity <a cascade of sound> <a cascade of events>
4: One-pot, sequential reactions involving more than one intermediate, preferrably 1) leading to an increase in molecular complexity and 2) without changing reaction conditions
see: Chem. Commun., 2003, 551
CO2Me
PhH
H H H
HCO2MeH
1) H2, Pd/BaSO4 quinoline2) toluene, 100 °C
3 intermediates
Me
OH
Me Me 1,2-dichloroethane;
K2CO3, H2O, MeOH
2 intermediates
OOO
, TFA,
OMe
Me
Me H
MeH
HH
OP1
H
P2O
O
H
CH3
O
H3C
H3CH
P1OH
H
H
H
H
CH3
RO
H3C
PO
OP
OP
CH3
O
O ORSePh mCPBA, CH2Cl2;
40 °C, CHCl34 intermediates
Some Inspiration
Nicolaou, K. C., J. Amer. Chem. Soc., 1982, 5555
Ph
Johnson, W. S., J. Amer. Chem. Soc., 1971, 4330
Sorensen, E. J., J. Amer. Chem. Soc., 2002, 4552
CO2Me
PhH
H H H
HCO2MeH
1) H2, Pd/BaSO4 quinoline2) toluene, 100 °C
3 intermediates
Me
OH
Me Me 1,2-dichloroethane;
K2CO3, H2O, MeOH
2 intermediates
OOO
, TFA,
OMe
Me
Me H
MeH
HH
OP1
H
P2O
O
H
CH3
O
H3C
H3CH
P1OH
H
H
H
H
CH3
RO
H3C
PO
OP
OP
CH3
O
O ORSePh mCPBA, CH2Cl2;
40 °C, CHCl34 intermediates
Some Inspiration
Nicolaou, K. C., J. Amer. Chem. Soc., 1982, 5555
Ph
Johnson, W. S., J. Amer. Chem. Soc., 1971, 4330
Sorensen, E. J., J. Amer. Chem. Soc., 2002, 4552
CO2Me
PhH
H H H
HCO2MeH
1) H2, Pd/BaSO4 quinoline2) toluene, 100 °C
3 intermediates
Me
OH
Me Me 1,2-dichloroethane;
K2CO3, H2O, MeOH
2 intermediates
OOO
, TFA,
OMe
Me
Me H
MeH
HH
OP1
H
P2O
O
H
CH3
O
H3C
H3CH
P1OH
H
H
H
H
CH3
RO
H3C
PO
OP
OP
CH3
O
O ORSePh mCPBA, CH2Cl2;
40 °C, CHCl34 intermediates
Some Inspiration
Nicolaou, K. C., J. Amer. Chem. Soc., 1982, 5555
Ph
Johnson, W. S., J. Amer. Chem. Soc., 1971, 4330
Sorensen, E. J., J. Amer. Chem. Soc., 2002, 4552
NH
O
OPh
OEtO
NH
OH
H
O
EtO
O
Ph
O, hu
Dihydropyridone Synthesis
N
O
OO
H
HH N
O
OHO
MeO2C
Ph
PhMeO2C
N OO
PhMeO2C
N
O
OHO
HH
MeO2C
Ph
O
H
Chem. Pharm. Bull., 1987, 4730
-CO
NH
O
OPh
OEtO
NH
OH
H
O
EtO
O
Ph
O, hu
Dihydropyridone Synthesis
N
O
OO
H
HH N
O
OHO
MeO2C
Ph
PhMeO2C
N OO
PhMeO2C
N
O
OHO
HH
MeO2C
Ph
O
H
Chem. Pharm. Bull., 1987, 4730
-CO
NH
O
OPh
OEtO
NH
OH
H
O
EtO
O
Ph
O, hu
Dihydropyridone Synthesis
N
O
OO
H
HH N
O
OHO
MeO2C
Ph
PhMeO2C
N OO
PhMeO2C
N
O
OHO
HH
MeO2C
Ph
O
H
Chem. Pharm. Bull., 1987, 4730
-CO
N
O
OO
H
HH
MeO2C
Ph
NH
O
OPh
OEtO
NH
OH
H
O
EtO
O
Ph
O, hu
Dihydropyridone Synthesis
N
O
OO
H
HH N
O
OHO
MeO2C
Ph
PhMeO2C
N OO
PhMeO2C
N
O
OHO
HH
MeO2C
Ph
O
H
Chem. Pharm. Bull., 1987, 4730
-CO
NH
O
OPh
OEtO
NH
OH
H
O
EtO
O
Ph
O, hu
Dihydropyridone Synthesis
N
O
OO
H
HH N
O
OHO
MeO2C
Ph
PhMeO2C
N OO
PhMeO2C
N
O
OHO
HH
MeO2C
Ph
O
H
Chem. Pharm. Bull., 1987, 4730
-CO
NH
O
OPh
OEtO
NH
OH
H
O
EtO
O
Ph
O, hu
Dihydropyridone Synthesis
N
O
OO
H
HH N
O
OHO
MeO2C
Ph
PhMeO2C
N OO
PhMeO2C
N
O
OHO
HH
MeO2C
Ph
O
H
Chem. Pharm. Bull., 1987, 4730
-CO
Degredation to a Cyclohexadiene
BrBr
HHCH3Li
Et2O
Angew. Chem. Int. Ed., 1975, 765.
CH3Li
Degredation to a Cyclohexadiene
BrBr
HHCH3Li
Et2O
Angew. Chem. Int. Ed., 1975, 765.
CH3Li
Degredation to a Cyclohexadiene
BrBr
HHCH3Li
Et2O
Angew. Chem. Int. Ed., 1975, 765.
CH3Li
Degredation to a Cyclohexadiene
BrBr
HHCH3Li
Et2O
Angew. Chem. Int. Ed., 1975, 765.
CH3Li
Degredation to a Cyclohexadiene
BrBr
HHCH3Li
Et2O
Angew. Chem. Int. Ed., 1975, 765.
CH3Li
Starting Material?
BrBr H
H
LiBr
CH2I2,Zn/Cu
CHBr3,KOtBu
MeLiEt2O
1. CH2I2, Zn/Cu2. CHBr3
3. MeLi, Et2O
Angew. Chem. Intern. Ed., 1975, 496
Starting Material?
BrBr H
H
LiBr
CH2I2,Zn/Cu
CHBr3,KOtBu
MeLiEt2O
1. CH2I2, Zn/Cu2. CHBr3
3. MeLi, Et2O
Angew. Chem. Intern. Ed., 1975, 496
Starting Material?
BrBr H
H
LiBr
CH2I2,Zn/Cu
CHBr3,KOtBu
MeLiEt2O
1. CH2I2, Zn/Cu2. CHBr3
3. MeLi, Et2O
Angew. Chem. Intern. Ed., 1975, 496
Starting Material?
BrBr H
H
LiBr
CH2I2,Zn/Cu
CHBr3,KOtBu
MeLiEt2O
1. CH2I2, Zn/Cu2. CHBr3
3. MeLi, Et2O
Angew. Chem. Intern. Ed., 1975, 496
Starting Material?
BrBr H
H
LiBr
CH2I2,Zn/Cu
CHBr3,KOtBu
MeLiEt2O
1. CH2I2, Zn/Cu2. CHBr3
3. MeLi, Et2O
Angew. Chem. Intern. Ed., 1975, 496
Synthesis of a Tetrayne
AcOH
BuLi; CuCl
AcOLi
Cu
AcO
Cu+
Cu+
BuLi
Symmetry Forbidden
Tetrahedron Lett., 1976, 2663
Synthesis of a Tetrayne
AcOH
BuLi; CuCl
AcOLi
Cu
AcO
Cu+
Cu+
BuLi
Symmetry Forbidden
Tetrahedron Lett., 1976, 2663
Synthesis of a Tetrayne
AcOH
BuLi; CuCl
AcOLi
Cu
AcO
Cu+
Cu+
BuLi
Symmetry Forbidden
Tetrahedron Lett., 1976, 2663
Synthesis of a Tetrayne
AcOH
BuLi; CuCl
AcOLi
Cu
AcO
Cu+
Cu+
BuLi
Symmetry Forbidden
Tetrahedron Lett., 1976, 2663
Synthesis of a Tetrayne
AcOH
BuLi; CuCl
AcOLi
Cu
AcO
Cu+
Cu+
BuLi
Symmetry Forbidden
Tetrahedron Lett., 1976, 2663
Complex Polycycle
SiMe3HOHO Br SnBu3
Bu3Sn
Pd(PPh3)4PhH, D
SiMe3HOHO PdLnBr
SiMe3HOHO PdLnBr
SiMe3HOHO
SnBu3
OH
H
HOSiMe3
OxidativeAddition
Migratory Insertion Transmetallation
SnBu3Bu3Sn
J. Am. Chem. Soc., 2001, 12107
Complex Polycycle
SiMe3HOHO Br SnBu3
Bu3Sn
Pd(PPh3)4PhH, D
SiMe3HOHO PdLnBr
SiMe3HOHO PdLnBr
SiMe3HOHO
SnBu3
OH
H
HOSiMe3
OxidativeAddition
Migratory Insertion Transmetallation
SnBu3Bu3Sn
J. Am. Chem. Soc., 2001, 12107
Complex Polycycle
SiMe3HOHO Br SnBu3
Bu3Sn
Pd(PPh3)4PhH, D
SiMe3HOHO PdLnBr
SiMe3HOHO PdLnBr
SiMe3HOHO
SnBu3
OH
H
HOSiMe3
OxidativeAddition
Migratory Insertion Transmetallation
SnBu3Bu3Sn
J. Am. Chem. Soc., 2001, 12107
Complex Polycycle
SiMe3HOHO Br SnBu3
Bu3Sn
Pd(PPh3)4PhH, D
SiMe3HOHO PdLnBr
SiMe3HOHO PdLnBr
SiMe3HOHO
SnBu3
OH
H
HOSiMe3
OxidativeAddition
Migratory Insertion Transmetallation
SnBu3Bu3Sn
J. Am. Chem. Soc., 2001, 12107
Complex Polycycle Cont...
OH
H
HOSiMe3
SiMe3HOHO
SnBu3H
SiMe3OH
HO
H
SiMe3O
H
O H
-
-
SiMe3HOHO
SnBu3
6 e- disrotatory
1H transfer
J. Am. Chem. Soc., 2001, 12107
SiMe3HOHO
SnBu3H
SiMe3HOHO
SnBu3H
Complex Polycycle Cont...
OH
H
HOSiMe3
SiMe3HOHO
SnBu3H
SiMe3OH
HO
H
SiMe3O
H
O H
-
-
SiMe3HOHO
SnBu3
6 e- disrotatory
1H transfer
J. Am. Chem. Soc., 2001, 12107
A [3.2.0] BicycleJ. Org. Chem., 1994, 8092
HO
MeO2C H
OTBDPS
H CO2Me
OTMS
I
TBDPSO
HTMSI, (TMS)2NH
OHTBDPSO CO2Me
H
SiMe3
N+
HTMSTMS
I-
OHTBDPSO CO2Me
H
TMS
OHTBDPSO
H
I OMeO
TMS2NH
Si I
I
A [3.2.0] BicycleJ. Org. Chem., 1994, 8092
HO
MeO2C H
OTBDPS
H CO2Me
OTMS
I
TBDPSO
HTMSI, (TMS)2NH
OHTBDPSO CO2Me
H
SiMe3
N+
HTMSTMS
I-
OHTBDPSO CO2Me
H
TMS
OHTBDPSO
H
I OMeO
TMS2NH
Si I
I
A [3.2.0] BicycleJ. Org. Chem., 1994, 8092
HO
MeO2C H
OTBDPS
H CO2Me
OTMS
I
TBDPSO
HTMSI, (TMS)2NH
OHTBDPSO CO2Me
H
SiMe3
N+
HTMSTMS
I-
OHTBDPSO CO2Me
H
TMS
OHTBDPSO
H
I OMeO
TMS2NH
Si I
I
A [3.2.0] BicycleJ. Org. Chem., 1994, 8092
HO
MeO2C H
OTBDPS
H CO2Me
OTMS
I
TBDPSO
HTMSI, (TMS)2NH
OHTBDPSO CO2Me
H
SiMe3
N+
HTMSTMS
I-
OHTBDPSO CO2Me
H
TMS
OHTBDPSO
H
I OMeO
TMS2NH
Si I
I
A [3.2.0] BicycleJ. Org. Chem., 1994, 8092
HO
MeO2C H
OTBDPS
H CO2Me
OTMS
I
TBDPSO
HTMSI, (TMS)2NH
OHTBDPSO CO2Me
H
SiMe3
N+
HTMSTMS
I-
OHTBDPSO CO2Me
H
TMS
OHTBDPSO
H
I OMeO
TMS2NH
Si I
I
A [3.2.0] BicycleJ. Org. Chem., 1994, 8092
HO
MeO2C H
OTBDPS
H CO2Me
OTMS
I
TBDPSO
HTMSI, (TMS)2NH
OHTBDPSO CO2Me
H
SiMe3
N+
HTMSTMS
I-
OHTBDPSO CO2Me
H
TMS
OHTBDPSO
H
I OMeO
TMS2NH
Si I
I
A HydrindaneUnpublished
O
O
OPPh3H
H
O
OH
H
H
H
OPhH, D
PPh3
O
P(O)Ph3
A HydrindaneUnpublished
O
O
OPPh3H
H
O
OH
H
H
H
OPhH, D
PPh3
O
P(O)Ph3
A HydrindaneUnpublished
O
O
OPPh3H
H
O
OH
H
H
H
OPhH, D
PPh3
O
P(O)Ph3
Another (the same) HydrindaneHoye, T., Unpublished
OHBn OBn
OHBn OHBn
H
H
H
Bn Bn
H HHO HO
H HHHO
Bn
H
H
Grubbs
Another (the same) HydrindaneHoye, T., Unpublished
OHBn OBn
OHBn OHBn
H
H
H
Bn Bn
H HHO HO
H HHHO
Bn
H
H
Grubbs
Another (the same) HydrindaneHoye, T., Unpublished
OHBn OBn
OHBn OHBn
H
H
H
Bn Bn
H HHO HO
H HHHO
Bn
H
H
Grubbs
NH
O
OPh
OEtO
NH
OH
H
O
EtO
O
Ph
O, hu
BrBr
HHCH3LiEt2O
AcOH
BuLi; CuCl
SiMe3HOHO Br SnBu3
Bu3Sn
Pd(PPh3)4PhH, D
OH
H
HOSiMe3
H CO2Me
OTMSIH
(TMS)2NHTMSI
OTBDPS
HO
H
OTBDPS
MeO2C
OHBn OBn
H
HGrubbs
MeLi, Et2OBrBr
O
O
OPPh3H
H
H
H
O
PhH, D
Summary
