total synthesis of ( ‒ )-colombiasin a and ( ‒ )-elisapterosin b by two different approaches
DESCRIPTION
Total Synthesis of ( ‒ )-Colombiasin A and ( ‒ )-Elisapterosin B by two different approaches. A presentation by Guillaume Pelletier April 27 th 2012. Structural and biological analysis. - PowerPoint PPT PresentationTRANSCRIPT
Total Synthesis of (Total Synthesis of (‒‒)-)-Colombiasin A and Colombiasin A and ((‒‒)-)-Elisapterosin B by two Elisapterosin B by two different approachesdifferent approaches
A presentation by Guillaume PelletierApril 27th 2012
Me O
O
Me
OH
H
Me
H
Me
( )-Colombiasin A
Me
HMe
OH
HMe
Me O
O
( )-Elisapterosin B
Structural and biological analysis Structural and biological analysis
These molecules are additions to the family of diterpenes from the gorgonian octacoral Pseudopterogorgia elisabethae (isolated by Rodriguez et al. in early 2000)
Possess potential antiplasmodial activity against plasmodium falciparum, the parasite responsible for the most severe forms of malaria and is an in vitro inhibitor of Mycobacterium tuberculosis H37Rb
Total synthesis by many groups : Harrowven (2005, ■ and ■), Nicolaou (2001, ■), Rychnovsky (2003, ■ and ■), Rawal (2003, ■), Davies (2006, ■), Jacobsen and Boezio, A. A. (2005, ■ and ■)
Me O
O
Me
OH
H
Me
H
Me
( )-Colombiasin A
Me
HMe
OH
HMe
Me O
O
( )-Elisapterosin B
Nicolaou, K. C.; Edmonds, D. J.; Bulger, P. G. Angew. Chem., Int. Ed. 2006, 45, 7134-7186.
Various approaches to the targetsVarious approaches to the targets
Me O
O
Me
OH
H
Me
H
Me
( )-Colombiasin A
Me
HMe
OH
HMe
Me O
O
( )-Elisapterosin B
LA, rt
Harrowvenm D. C.; Pascoe, D. D.; Demurtas, D.; Bourne, H. O. Angew. Chem., Int. Ed. 2005, 44, 1221-1222.Waizumi, N.; Stankovic, A. R.; Rawal, V. R. J. Am. Chem. Soc. 2003, 125, 13022-13023.
Me O
O
Me
OH
H
Me
H
Me
( )-Colombiasin A
O
O
Me
H
Ot-Bu
Me
Me
H
OHMe
H
O
Me
HMe
OH
HMe
Me O
O
( )-Elisapterosin B
Me
HMe
OO
OHMe
Me
OMeMeO
CO2MeMe
OO
CO2H
Harrowven’s approach to (Harrowven’s approach to (‒)-‒)-Colombiaisin AColombiaisin A
Harrowvenm D. C.; Pascoe, D. D.; Demurtas, D.; Bourne, H. O. Angew. Chem., Int. Ed. 2005, 44, 1221-1222.
OLiAlH4
88% ?
Harrowven’s approach to (Harrowven’s approach to (‒)-‒)-Colombiaisin AColombiaisin A
OLiAlH4
OH
88%
O
Me
Axial reduction
H
(( )-ipc)2BH
then H2O2, NaOH
Me
OH
Me
OH
+H H
OH OH
2 : 5
Separable isomers
98%
Harrowvenm D. C.; Pascoe, D. D.; Demurtas, D.; Bourne, H. O. Angew. Chem., Int. Ed. 2005, 44, 1221-1222.
Harrowven’s approach to (Harrowven’s approach to (‒)-‒)-Colombiaisin AColombiaisin A
Brown, H. C.; Singaram, B. Acc. Chem. Res. 1988, 21, 287-298.Brown, H. C.; Ramachandran, P. V. J. Organomet. Chem. 1995, 500, 1-19.
Matteson, D. S. Synthesis 1996, 973-985.
OLiAlH4
OH
88%
O
Me
Axial reduction
H
(( )-ipc)2BH
then H2O2, NaOH
Me
OH
Me
OH
+H H
OH OH
2 : 5
Separable isomers
98%
Harrowven’s approach to (Harrowven’s approach to (‒)-‒)-Colombiaisin AColombiaisin A
R
H H
R
OLiAlH4
OH
88%
O
Me
Axial reduction
H
(( )-ipc)2BH
then H2O2, NaOH
Me
OH
Me
OH
+H H
OH OH
2 : 5
Separable isomers
98%
H
MeOH
H H
MeOH
H
HMe
H
HHO
B H
2
2 3
4
B H
LS
MM
LS
H
R R
H
B H
LS
MM
LS
Good enantioselectivity(75-90%)
Low enantioselectivity(5-30%)
vs
E alkenes
Z and cyclicalkenes
Brown, H. C.; Singaram, B. Acc. Chem. Res. 1988, 21, 287-298.Brown, H. C.; Ramachandran, P. V. J. Organomet. Chem. 1995, 500, 1-19.
Matteson, D. S. Synthesis 1996, 973-985.
Harrowven’s approach to (Harrowven’s approach to (‒)-‒)-Colombiaisin AColombiaisin A
OLiAlH4
OH
88%
O
Me
Axial reduction
H
(( )-ipc)2BH
then H2O2, NaOH
Me
OH
Me
OH
+H H
OH OH
2 : 5
Separable isomers
98%
1) TsCl, Et3N, DCM, rt, 3 h2) NaCN, DMSO, 100 °C, 1 h3) DIBAL-H, toluene, 0 °C, 1 h
Me
OH
H
40% over 3 steps
O
Harrowvenm D. C.; Pascoe, D. D.; Demurtas, D.; Bourne, H. O. Angew. Chem., Int. Ed. 2005, 44, 1221-1222.
Harrowven’s approach to (Harrowven’s approach to (‒)-‒)-Colombiaisin AColombiaisin A
OLiAlH4
OH
88%
O
Me
Axial reduction
H
(( )-ipc)2BH
then H2O2, NaOH
Me
OH
Me
OH
+H H
OH OH
2 : 5
Separable isomers
98%
1) TsCl, Et3N, DCM, rt, 3 h2) NaCN, DMSO, 100 °C, 1 h3) DIBAL-H, toluene, 0 °C, 1 h
Me
OH
H
40% over 3 steps
N
S
S
OO
+
NaHMDS (2.0 equiv)DME, 60 °C to rt
79%, 3:1 Z:E
Me
OH
H
O
H
Harrowvenm D. C.; Pascoe, D. D.; Demurtas, D.; Bourne, H. O. Angew. Chem., Int. Ed. 2005, 44, 1221-1222.
Kocienski’s modification of Julia Kocienski’s modification of Julia olefination (BT sulfone)olefination (BT sulfone)
Baudin, J. B.; Hareau, G.; Julia, S. H.; Lorne, R.; Ruel, O. Bull. Chim. Soc. Fr. 1993, 130, 856-878.Smith, N. D.; Kocienski, P. J.; Street, D. A. S. Synthesis 1996, 652-666.
S
O O
S
N R
O
H+
MHMDS"Solvent"
R
"BT"
SO2BT
OM
R
SO2BT
OM
anti
syn
MHMDS"Solvent"
S
O
MO
H
O
NS
R
H
O
H R
H
SOMO
BT
Open TS
Cyclic TS
S
R
MO
H
O
BT
O
H
S
HO
H
O
NS
R
OM
S
RO
H
O
NS
H
OM
Fast
Slow O
R H
S
H
OO
N
S
M
O
H R
S
H
OO
N
S
M
OBt
R H
H
SO2M
OBt
H R
H
SO2M
R
R
E alkene
Z alkene
Kocienski’s modification of Julia Kocienski’s modification of Julia olefination (BT sulfone)olefination (BT sulfone)
Baudin, J. B.; Hareau, G.; Julia, S. H.; Lorne, R.; Ruel, O. Bull. Chim. Soc. Fr. 1993, 130, 856-878.Smith, N. D.; Kocienski, P. J.; Street, D. A. S. Synthesis 1996, 652-666.
Cyclic (Chelate) TS favoured for non-polar solvent, small counter-ions (Li)Open TS favoured for polar solvents, large counter-ions (K)
S
O O
S
N R
O
H+
MHMDS"Solvent"
R
"BT"
SO2BT
OM
R
SO2BT
OM
anti
syn
MHMDS"Solvent"
S
O
MO
H
O
NS
R
H
O
H R
H
SOMO
BT
Open TS
Cyclic TS
S
R
MO
H
O
BT
O
H
S
HO
H
O
NS
R
OM
S
RO
H
O
NS
H
OM
Fast
Slow O
R H
S
H
OO
N
S
M
O
H R
S
H
OO
N
S
M
OBt
R H
H
SO2M
OBt
H R
H
SO2M
R
R
E alkene
Z alkene
Kocienski’s modification of Julia Kocienski’s modification of Julia olefination (BT sulfone)olefination (BT sulfone)
Charette, A. B.; Lebel, H. J. Am. Chem. Soc. 1996, 118, 10327-10328.
Cyclic (Chelate) TS favoured for non-polar solvent, small counter-ions (Li)Open TS favoured for polar solvents, large counter-ions (K)
O
NH
( )-U-106305
OHC OTIPS Me SO2BT OTIPSMHMDS
-78 °C to rt+
Solvent Base E:Z ratio
DMF
DME
THF
THF
Et2O
DCM
toluene
toluene
NaHMDS
NaHMDS
NaHMDS
KHMDS
NaHMDS
NaHMDS
NaHMDS
KMHDS
3.5 : 1
2.4 : 1
1.1 : 1
1.2 : 1
1 : 7.7
1 : 10
1 : 10
1 : 3.7
Harrowven’s approach to (Harrowven’s approach to (‒)-‒)-Colombiaisin AColombiaisin A
Me
OH
H
H
(COCl)2, DMSODCM, -78 °C
then Et3N, -78 °C to rt
93%, 3 : 1 (Z : E)Me
O
H
H
I2 (10 mol%)DCM, rt, 2 h
99%, 1 : 99< (Z : E)Me
O
H
H
i) TrisNHNH2, THF, rt, 2 hii) -78 °C, then t-BuLi (4.0 equiv)iii)
Me
t-BuO O
O
20 min-78°C to rt
Me
H
H
OH O
t-BuOMe
Me
H
H
36%major product
if TsNHNH2 or isolation after i)
Harrowvenm D. C.; Pascoe, D. D.; Demurtas, D.; Bourne, H. O. Angew. Chem., Int. Ed. 2005, 44, 1221-1222.
Modified Bamford-Stevens (Shapiro) Modified Bamford-Stevens (Shapiro) olefination olefination
Harrowvenm D. C.; Pascoe, D. D.; Demurtas, D.; Bourne, H. O. Angew. Chem., Int. Ed. 2005, 44, 1221-1222.Reed, M. W.; Pollart, D. J.; Perri, S. T.; Foland, L. D.; Moore, H. W. J. Org. Chem. 1988, 53, 2477 – 2482.
Shapiro, R. H. Org. React. 1976, 26, 405-507.
Me
O
H
H
Me
t-BuO O
O
20 min-78°C to rt
Me
H
H
OH O
t-BuOMe
TrisNHNH2 =
HNNH2
TrisNHNH2
THF, rt, 2 h
Me
OHH
H
NH NH
Tris
H2O
Me
H
H
NNH
Tris
t-BuLi, -78 °C
Me
H
H
NNLi
Trist-BuLi, -78 °C
Me
H
H
NNLi
Me
H
H
Li
N2
TrisLi
+ H2O
Me
H
H
Casanova, J.; Waegell, B. Bull. Chim. Soc. Fr. 1975, 922-932.Nickon, A.; Bronfenbrenner, J. K. J. Am. Chem. Soc. 1982, 104, 2022-2023.
Bamford-Stevens olefination in protic Bamford-Stevens olefination in protic and aprotic solvents and aprotic solvents
R
NNH
Ts
R'
NaOMe
R
NN
Ts
R'
Na+
R
N
R'
N
TsNa+
R
N
R'
N
+SolventH
R
N
R'
N
H+
RR'
H+
H H
N2
Solvent
RR'
H
H
R
N
R'
N
+
R
N
R'
N
+
N2
RR'
H H
1,2-Hydride
shift
RR'
H
H
Harrowven’s approach to (Harrowven’s approach to (‒)-‒)-Colombiaisin AColombiaisin A
Me
OH
H
H
(COCl)2, DMSODCM, -78 °C
then Et3N, -78 °C to rt
93%, 3 : 1 (Z : E)Me
O
H
H
I2 (10 mol%)DCM, rt, 2 h
99%, 1 : 99< (Z : E)Me
O
H
H
i) TrisNHNH2, THF, rt, 2 hii) -78 °C, then t-BuLi (4.0 equiv)iii)
Me
t-BuO O
O
20 min-78°C to rt
Me
H
H
OH O
t-BuOMe
Me
H
H
36%major product
if TsNHNH2 or isolation after i)
wave, 110 °C, THF
then air, rt
Me
H
O
O
Ot-Bu
Me
80%
Harrowvenm D. C.; Pascoe, D. D.; Demurtas, D.; Bourne, H. O. Angew. Chem., Int. Ed. 2005, 44, 1221-1222.
Moore rearrangement of Moore rearrangement of vinylcyclobutene to hydroquinonevinylcyclobutene to hydroquinone
Harrowvenm D. C.; Pascoe, D. D.; Demurtas, D.; Bourne, H. O. Angew. Chem., Int. Ed. 2005, 44, 1221-1222.Karlsson, J. O.; Nguyen, N. V.; Foland, L. D.; Moore, H. W. J. Am. Chem. Soc. 1985, 107, 3392-3393.
Perri, S. T.; Dyke, H. J.; Moore, H.W. J. Org. Chem. 1989, 54, 2032-2034.
Me
H
H
OH O
t-BuOMe
wave, 110 °C, THF
then air, rt
4 electrocycloreversion
Me
H
OH
Ot-Bu
MeO
• 6 electrocyclisation
Me
H
OH
Ot-Bu
Me
OH
Tautomerisation
Me
H
OH
Ot-Bu
Me
OH
air, rt, THF
Oxidation
Me
H
O
Ot-Bu
Me
O 2 H+
2 é
Harrowven’s approach to (Harrowven’s approach to (‒)-‒)-Colombiaisin AColombiaisin A
Me
H
O
O
Ot-Bu
Me
Me O
O
Me
OH
H
Me
H
Me
( )-Colombiasin A
1) toluene, 150 °C, 60 %
2) BF3OEt2 (2.0 equiv)0 °C, DCM, 5 min, 78 %
Harrowvenm D. C.; Pascoe, D. D.; Demurtas, D.; Bourne, H. O. Angew. Chem., Int. Ed. 2005, 44, 1221-1222.
To be continued…
Rawal’s approach to (Rawal’s approach to (‒)-‒)-Elisapterosin Elisapterosin BB
Waizumi, N.; Stankovic, A. R.; Rawal, V. R. J. Am. Chem. Soc. 2003, 125, 13022-13023.
NH2
CO2HHO2CNaNO2 (1.5 equiv)
Dioxane:H2O (1:8)HCl [1.0 M], 0-5 °C
then, rt, 2 h
OO
CO2H
76%, 95% ee
(COCl)2 (2.5 equiv)
DMF cat. DCM0 °C to rt, 2 h
OO
COCl
commercialPfaltz & Bauer, Inc
(Acid ~60$/g Aldrich!)
Diazotization with HNODiazotization with HNO22
ON O
Na+
HCl HON O
HCl ON O
HH
+Cl
N O+
N O+
CO2HHO2C
NH2
N O+
CO2HHO2C
HNN
O
CO2HHO2C
NN
OH
+ HCl
CO2HHO2C
NN
OH2+
H2OCO2H
NN+
O
HO
N2
SN2O
CO2H
OH
H
+
HCl
nitrosonium ion
N-nitrosamine diazenol
diazenium ion
Carey, F. A.; Sundberg, R. J. in “Advanced Organic Chemistry”, Springer, ed.; 4th Edition, Chap.
Rawal’s approach to (Rawal’s approach to (‒)-‒)-Elisapterosin Elisapterosin BB
NH2
CO2HHO2CNaNO2 (1.5 equiv)
Dioxane:H2O (1:8)HCl [1.0 M], 0-5 °C
then, rt, 2 h
OO
CO2H
76%, 95% ee
(COCl)2 (2.5 equiv)
DMF cat. DCM0 °C to rt, 2 h
OO
COCl
commercialPfaltz & Bauer, Inc
(Acid ~60$/g Aldrich!)
MeO
Me
OMe
BrMg
ZnCl, Pd(PPh3)2Cl2 cat.THF
OO
O
OMe
Me
OMe
75% over 2 steps
(OMe)3CH TsOH cat. MeOH
then, t-BuOK, THFOO OMe
Me
OMe
OMeOMe
83%
NaHMDS
MeI, THFOO OMe
Me
OMe
OMeOMe
Me
8 : 1 dr, 86%
Waizumi, N.; Stankovic, A. R.; Rawal, V. R. J. Am. Chem. Soc. 2003, 125, 13022-13023.Negishi, E.; Bagheri, V.; Chatterjee, S.; Luo, F. T.; Miller, J. A.; Stoll, A. T. Tetrahedron Lett. 1983, 24, 5181-5184.
Rawal’s approach to (Rawal’s approach to (‒)-‒)-Elisapterosin Elisapterosin BB
Waizumi, N.; Stankovic, A. R.; Rawal, V. R. J. Am. Chem. Soc. 2003, 125, 13022-13023.Negishi, E.; Bagheri, V.; Chatterjee, S.; Luo, F. T.; Miller, J. A.; Stoll, A. T. Tetrahedron Lett. 1983, 24, 5181-5184.
NH2
CO2HHO2CNaNO2 (1.5 equiv)
Dioxane:H2O (1:8)HCl [1.0 M], 0-5 °C
then, rt, 2 h
OO
CO2H
76%, 95% ee
(COCl)2 (2.5 equiv)
DMF cat. DCM0 °C to rt, 2 h
OO
COCl
commercialPfaltz & Bauer, Inc
(Acid ~60$/g Aldrich!)
MeO
Me
OMe
BrMg
ZnCl, Pd(PPh3)2Cl2 cat.THF
OO
O
OMe
Me
OMe
75% over 2 steps
(OMe)3CH TsOH cat. MeOH
then, t-BuOK, THFOO OMe
Me
OMe
OMeOMe
83%
NaHMDS
MeI, THFOO OMe
Me
OMe
OMeOMe
Me
8 : 1 dr, 86%
H
OH
HONa
MeO OMe
Ar
Rawal’s approach to (Rawal’s approach to (‒)-‒)-Elisapterosin Elisapterosin BB
Waizumi, N.; Stankovic, A. R.; Rawal, V. R. J. Am. Chem. Soc. 2003, 125, 13022-13023.
OO OMe
Me
OMe
OMeOMe
Me
1) DIBAL-H, toluene
2) Seyfert's reagentt-BuOK, THF Me OH
MeO OMeOMe
Me
OMe
70% over 2 steps
Seyfert-Gilbert alkynylationSeyfert-Gilbert alkynylation
Waizumi, N.; Stankovic, A. R.; Rawal, V. R. J. Am. Chem. Soc. 2003, 125, 13022-13023.
Seyferth, D.; Marmor, R. S.; Hilbert, P. J. Org. Chem. 1971, 36, 1379-1386.Colvin, E. W.; Hamill, B. J. J. Chem. Soc., Chem. Commun.1973, 151-152.
Gilbert, J. C.; Weerasooriya, U. J. Org. Chem. 1979, 44, 4997-4998.
OO OMe
Me
OMe
OMeOMe
Me
1) DIBAL-H, toluene
2) Seyfert's reagentt-BuOK, THF Me OH
MeO OMeOMe
Me
OMe
70% over 2 steps
DIBAL-H
OHO OMe
Me
OMe
OMeOMe
Me
H2O, H3O+
Me OH
MeO OMeOMe
Me
OMe
O
H
O
P
N2
MeOMeO
R
OK
P
O
MeOMeO
N2
H
K+
P O
OKMeO
MeO
N2 R
H
N C
H
R
N+
N CH
H
R
N+
C
H
R+
O
POKMeO
OMe
Rawal’s approach to (Rawal’s approach to (‒)-‒)-Elisapterosin Elisapterosin BB
Waizumi, N.; Stankovic, A. R.; Rawal, V. R. J. Am. Chem. Soc. 2003, 125, 13022-13023.
OO OMe
Me
OMe
OMeOMe
Me
1) DIBAL-H, toluene
2) Seyfert's reagentt-BuOK, THF Me OH
MeO OMeOMe
Me
OMe
70% over 2 steps
1) MsCl, 2,6-lutidine, 50 °C2) CaCO3, wet MeOH, 50 °C
Me CO2Me
MeO
Me
OMe
72% over 2 steps
Pinacol-type rearrangment of ketalPinacol-type rearrangment of ketal
Me OH
MeO OMeOMe
Me
OMe
1) MsCl, 2,6-lutidine, 50 °C
2) CaCO3, wet MeOH, 50 °CMe CO2Me
MeO
Me
OMe
72% over 2 steps
MsCl, 2,6-lutidine
Me OMs
MeO OMeOMe
Me
OMe
OMe
Me
OMe
MeO OMe
Me+
MsO
H
Me
MeO
Me
OMe
O OMe
Me+
MsO
H2O
Tsuchihashi, G., Kitajima, K., Mitamura, M. Tetrahedron Lett. 1981, 22, 4305-4308.
Honda, Y.; Ori, A.; Tsuchihashi, G. Bull. Chem. Soc. Jpn. 1987, 60, 1027-1036.
Rawal’s approach to (Rawal’s approach to (‒)-‒)-Elisapterosin Elisapterosin BB
Waizumi, N.; Stankovic, A. R.; Rawal, V. R. J. Am. Chem. Soc. 2003, 125, 13022-13023.
OO OMe
Me
OMe
OMeOMe
Me
1) DIBAL-H, toluene
2) Seyfert's reagentt-BuOK, THF Me OH
MeO OMeOMe
Me
OMe
70% over 2 steps
1) MsCl, 2,6-lutidine, 50 °C2) CaCO3, wet MeOH, 50 °C
Me CO2Me
MeO
Me
OMe
72% over 2 steps
Me CO2Me
MeO
Me
OMeBr
1) AgNO3 cat.NBS (1.0 equiv)
Acetone, rt
2) TsNHNH2 (6.0 equiv)AcONa (7.0 equiv)
MeOH, reflux
Rawal’s approach to (Rawal’s approach to (‒)-‒)-Elisapterosin Elisapterosin BB
Waizumi, N.; Stankovic, A. R.; Rawal, V. R. J. Am. Chem. Soc. 2003, 125, 13022-13023.
Me CO2Me
MeO
Me
OMeBr
BrMe
(1.2 equiv)
t-BuLi (2.4 equiv), -78 °C
then ZnCl2 (1.2 equiv)PdCl2(dppf) (1.0 mol%)
THF, rtMe CO2Me
MeO
Me
OMe
Me
1) DIBAL-H, -95 °C2) PPh3CH(Me)2Br, n-BuLi3) NaSEt (10 equiv), DMF 90 °C
Me
HO
Me
OMe
Me
70%
42% over 3 steps
Me
O
Me
OMe
Me
O
49%
Salcomine (1.0 mol%)O2, DMF, rt
Rawal’s approach to (Rawal’s approach to (‒)-‒)-Elisapterosin Elisapterosin BB
Waizumi, N.; Stankovic, A. R.; Rawal, V. R. J. Am. Chem. Soc. 2003, 125, 13022-13023.
Me CO2Me
MeO
Me
OMeBr
BrMe
(1.2 equiv)
t-BuLi (2.4 equiv), -78 °C
then ZnCl2 (1.2 equiv)PdCl2(dppf) (1.0 mol%)
THF, rtMe CO2Me
MeO
Me
OMe
Me
1) DIBAL-H, -95 °C2) PPh3CH(Me)2Br, n-BuLi3) NaSEt (10 equiv), DMF 90 °C
Me
HO
Me
OMe
Me
70%
42% over 3 steps
Me
O
Me
OMe
Me
O
49%
Salcomine (1.0 mol%)O2, DMF, rt
O
N
N
O
Co
Salcomine
Salcomine catalyzed aerobic Salcomine catalyzed aerobic oxidation of phenoloxidation of phenol
Van Dort, H. M.; Geursen, H. J. Recl. Trav. Chim. Pays-Bas 1967, 86, 520-526. Parker, K. A.; Petraitis, J. J. Tetrahedron Lett. 1981, 22, 397-400.
Co2+(salen)
O2
HO
Me
OMe
O
Me
OMe
Co3+(salen)O
HO
HO
Me
OMe
OO
O2
O
Me
OMe
OO
Co3+(salen)O
O
Co3+(salen) O
OH
HO
Me
OMe
OOH H+
O
Me
OMe
O
H2O
Rawal’s approach to (Rawal’s approach to (‒)-‒)-Elisapterosin Elisapterosin BB
Waizumi, N.; Stankovic, A. R.; Rawal, V. R. J. Am. Chem. Soc. 2003, 125, 13022-13023.
Me
O
Me
OMe
Me
O
toluene, 80 °C
H
Me H
MeO
O
OMe
Me
1) RhCl(PPh3)3 cat., H2
2) LiI (4.0 equiv), lutidine, 80 °C
67%, endo only
H
Me H
MeO
O
OH
Me
99% over 2 steps
CAN, MeCN, 10 min
then Pyridine, Et3N, 50 °C
Me
HMe
OH
HMe
Me O
O
84%ent-()-Elisapterosin B
EndoEndo-selective Diels-Alder-selective Diels-Alder
Waizumi, N.; Stankovic, A. R.; Rawal, V. R. J. Am. Chem. Soc. 2003, 125, 13022-13023.
MeOMe
O
O
Me
H
Re face
MeH
Si face
Me
MeHO
O
OMe
Me
H
Avoids allylic tensionAllylic tension present
between propenyl and C-Me on the diene
favored
Me
H
H
O
O
OMe
Me
H
Me H
Rawal’s approach to (Rawal’s approach to (‒)-‒)-Elisapterosin Elisapterosin BB
Waizumi, N.; Stankovic, A. R.; Rawal, V. R. J. Am. Chem. Soc. 2003, 125, 13022-13023.
Me
O
Me
OMe
Me
O
toluene, 80 °C
H
Me H
MeO
O
OMe
Me
1) RhCl(PPh3)3 cat., H2
2) LiI (4.0 equiv), lutidine, 80 °C
67%, endo only
H
Me H
MeO
O
OH
Me
99% over 2 steps
CAN, MeCN, 10 min
then Pyridine, Et3N, 50 °C
Me
HMe
OH
HMe
Me O
O
84%ent-()-Elisapterosin B
CAN mediated oxidative cyclisation CAN mediated oxidative cyclisation
Waizumi, N.; Stankovic, A. R.; Rawal, V. R. J. Am. Chem. Soc. 2003, 125, 13022-13023.Zanoni, G.;Franzini, M. Angew. Chem., Int. Ed. 2004, 43, 4837-4841.
Me
H
H
O
O
OMe
Me
H
Me H
1) LiI, lutidine
2) (NH4)2Ce(NO3)6
Me
H
O
O
O
Me
H
Me
CeIV Me
H
O
O
O
Me
H
Me
CeIII
H
H
CeIV
CeIII
Me
H
O
O
O
Me
H
MeH
H
1,2-H ShiftMe
H
O
O
O
Me
H
MeH
H
Me
HMe
O
HMe
Me O
O HMe
HMe
OH
HMe
Me O
O
Et3N
Me
H
O
O
Ot-Bu
Me
Me O
O
Me
OH
H
Me
H
Me
( )-Colombiasin A
1) toluene, 150 °C, 60 %
2) BF3OEt2 (2.0 equiv)0 °C, DCM, 5 min, 78 %
BF3OEt2 (20.0 equiv)rt
Me
HMe
OH
HMe
Me O
O
( )-Elisapterosin B
((‒)-‒)-Colombiaisin A to (Colombiaisin A to (‒‒)-Elisapterosin )-Elisapterosin B with BFB with BF33••OEtOEt22
Boezio, A. A.; Jarvo, E. R.; Lawrence, B. M.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2005, 44, 6046-6050.
((‒)-‒)-Colombiaisin A to (Colombiaisin A to (‒‒)-Elisapterosin )-Elisapterosin B with BFB with BF33••OEtOEt22
Me O
O
Me
OH
H
Me
H
Me
( )-Colombiasin A
BF3OEt2 (20.0 equiv)rt
Me
HMe
O
HMe
Me O
O
( )-Elisapterosin B
retro Diels-Alder
Me O
O
Me
O
H
Me
H
Me
B
FF
+
Me
H
O
O
O
Me
B
FF
+
O
O
Me
OB
F
F
+H
Me
H[5+2]
Cycloaddition+
B
F
F
Me
HMe
OH
HMe
Me O
OH2O
quench
Boezio, A. A.; Jarvo, E. R.; Lawrence, B. M.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2005, 44, 6046-6050.
Nicolaou, K. C.; Edmonds, D. J.; Bulger, P. G. Angew. Chem., Int. Ed. 2006, 45, 7134-7186.