01.10.14
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1
Ring contraction reactions in
Total synthesis
Ruben Eckermann Gaich-Group Seminar
October 2nd, 2014
Gaich-‐Group Seminar Ruben Eckermann Overview
2
Exclusion of one heteroatom One-carbon contraction
- Eschenmoser contraction - Ramberg-Bäcklund reaction
- Photo-Fries rearrangement
- Wittig rearrangement
- Stevens rearrangement - Co-mediated O à C – contraction
- Zr-mediated O à C – contraction
à mostly used for macrocycles
- Wager-Meerwein/Pinacol rearrangements
- Epoxide rearrangement
- Favorski rearrangement
- oxidative contractions - Wolff rearrangement à mostly used for cyclopentyl units à Review: L. F. Silva, Jr. Tetrahedron
2002, 58, 9137-9161
Y- Y
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Gaich-‐Group Seminar Ruben Eckermann
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Exclusion of one heteroatom
Y- Y
Gaich-‐Group Seminar Ruben Eckermann
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Eschenmoser sulfide contraction
Synthesis of 1,3-dicarbonyls via S-alkylation:
SH
O
XO
n
base
PR3
S
O
OHn
S
OH
On
- S=PR3
OOH
n
X = I, Br, Cl, OTs, OMs S
HN
X
O base
PR3n N
SOH
nHN
SO
n HN
O
n
- S=PR3
X = I, Br, Cl, OTs, OMs
S
HNHN
n
BPO
then PR3
S
NHN
n
OR
N
SHN
nHN
SN
n HN
N
n
- S=PR3
S
HN
I
N base
PR3n N
SHN
nHN
SN
n HN
N
n
- S=PR3
S
HNHN
n
NIS
via enamine prefunctionalization:
via oxidation of sulfur:
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Gaich-‐Group Seminar Ruben Eckermann
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Vitamin B12 synthesis
A. Eschenmoser, C. E. Winter, Science 1977, 196, 1410 - 1420
NH
SO S
Me
Me
CO2Me
NH
OMe
Me
CO2Me
+
a) BPO, HCl (CH2Cl2) then P(OEt)3 (xylene), 125°C
43%
N
S
O
MeMe
H
CO2MeHN
MeMeS
H
CO2Me
N
Br
Me
NC
CO2Me
a) KOtBu (THF/tBuOH)b) P(CH2CH2CN)3 TFA, (sulfolane) 60°C
64%
N
MeH
CO2Me
HN
MeMe
H
CO2Me
N
Me
MeO2C
CN
a) NIS, (CH2Cl2), 0°C then
c) HNEt2 (MeOH)
CONEt2
NH
S
Me
MeNC
MeO2C
CO2Me
NaHMDS, (PhH/tBuOH)then Cd(ClO4)2, (MeOH)
N
MeH
CO2Me
N
MeMe
H
CO2Me
N
Me
MeO2C
CN
CONEt2
S
N
Me
MeNC
MeO2C
MeO2C
(Cl)Cd
1 23
4
56
7
Gaich-‐Group Seminar Ruben Eckermann
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Vitamin B12 synthesis
A. Eschenmoser, C. E. Winter, Science 1977, 196, 1410 - 1420
then PPh3, TFA(PhH), 80°C
46%
N
MeH
CO2Me
N
MeMe
H
CO2Me
N
Me
MeO2C
CN
CONEt2
N
Me
MeNC
MeO2C
MeO2C
(Cl)Cd
7
a) DBU, (sulfolane) 60°C then HOAc, Cd(ClO4) (MeOH)
b) hυ, visible (MeOH), 60°c) CoCl2, 58°C then KCN, O2, H2O (CH2Cl2), 0°C
46%
N
MeH
CO2Me
N
MeMe
H
CO2Me
N
Me
MeO2C
CN
CONEt2
N
MeMeO2C
MeO2C
8
HMe Co
CN
CN
N
MeH
CONH2
N
MeMe
H
CONH2
N
Me
H2NOC
CO2-
CONH2
N
MeH2NOC
H2NOC
Cobyric acid (9)
HMe Co
CN
CN
Me
Me
6
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Gaich-‐Group Seminar Ruben Eckermann
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1β-Methylcarbapenem
O. Sakurai, T. Ogiku, M. Takahashi, M. Hayashi, T. Yamanaka, H. Horikawa, J. Org. Chem. 1996, 61, 7889 - 7894
NHO
H HCO2H
TBSO a) CDI, HSCO2Et
CO2Et
b) HO
HO
O
O80%
NO
H HTBSO
S
OCO2Et
CO2Et
OH
O O
SOCl2, pyrthen iPr2NH
75% NO
H HTBSO
S
O
OO
a) NaH, PPh3 then (PhO)2POCl
b) iPr2NHHS
HN O
O66%
NO
H HTBSO
S
OO HN
O
O
10 11 12
13
NO
H HHO
S
OOH NH2
1β-Methylcarbapenem
6
5
Gaich-‐Group Seminar Ruben Eckermann
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Ramberg-Bäcklund rearrangement
S
X
n
baseS
n
O
O
O
O
heatn
X = I, Br, Cl, OTs, OMs
X
nSH
baseS
noxidation
Sn O
O
base
X+
via S-alkylation/oxidation:
via cycloaddition:
SO O
Cr(CO)3
+
hυ [6π+4π]then CO SO2
base
X+SO2
X
baseSO2
-SO2
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Gaich-‐Group Seminar Ruben Eckermann
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(+)-Fawcettidine
J. A. Kozak, G. R. Dake, Angew. Chem. Int. Ed. 2008, 47, 4221 - 4223
O
(+)-pulegone (14)
a) H2O2, LiOHb) NaH, HSPh
c) NaBO3, AcOH84%
OSO
Ph
15
DBU, (DMF), -40°Cthen CO2Me
then 40°C63%
O
16
CO2Me
a) BrMgCH2CH2CCTMS CuBr*SMe2, (THF) -78 to -40°C
b) TBAF, (THF)80%
O
17
CO2Me
SEtHN
ONH3
CF3CO2-
a) AcOH, (PhMe), 110°C
b) PtCl2 (10mol%) (PhMe), 90°Cc) SeO2, (1,4-dioxane) 85°C
33%18
N
O
HO
SEtHN
O
a) 1 M NaOHb) ethylene glycol PPTS, (PhH)
then mCPBA(CH2Cl2)
85%
N
O
H
Me
S
O
OH
H
19
O
Oa) CBr2F2, KOH (CH2Cl2/tBuOH)b) H2, Pd/C, (EtOH/THF)
then LiAlH4then 1 M HCl
11%
N
H
Me HH
(+)-fawcettidine (20)
O
8 7
Gaich-‐Group Seminar Ruben Eckermann
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(+)-Estradiol
J. H. Rigby, N. C. Warshakoon, A. J. Payen, J. Am. Chem. Soc.. 1999, 121, 8237 - 8245
Me O
OH
CO2H
Me OTBS
H
SO O
a) (TMSCCH)Co2(CO)6 (PhMe), refluxb) Br2, NEt3
c) (MeCN)3Cr(CO)3 (THF)
18%
S
TMS
O O
Cr(CO)3
Me OTBS
HSO2
TMS
1) hυ2) CO
70%
a) KOtBu, -105°C then NCSb) KOtBu, -105°C
65%
TMS
Me OTBS
H H
a) KNH(CH2)3NH2 (THF), rtb) HF, (MeCN)
c) Et3SiH, TFA27%
TMS
Me OH
H H
H Pb(OTFA)4, TFA
80%
HO
Me OH
H H
H
2122
2324
25 26
27 (+)-estradiol (28)
77
66
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Gaich-‐Group Seminar Ruben Eckermann
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Photo-Fries rearrangement
HO
CO2Hn
OO
ncoupling hυ
OO
n
OO
n
OO
n
HOO
n
HOO
n
Gaich-‐Group Seminar Ruben Eckermann
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Kendomycin
H. J. Martin, T. Magauer, J. Mulzer, Angew. Chem. Int. Ed. 2010, 49, 5614 - 5626
MeOMe
MOMO
O
HO2C
Me
+Me
OH
OTBDPS
29 30
a) EDCI, DAMP
b) LDA, TBSCl71%
Me
OMeMOMO
O
MeOH
OMe
OTBDPS
31
a) LiAlH4b) MsCl
c) LiAlH494% Me
OMeMOMO
O
Me
MeMe
OTBDPS
32
a) TBAFb) IBXc) Sn(OTf)2, 33
d) NMe4BH(OAc)3e) LiOH, H2O2
52% Me
OMeMOMO
O
Me
MeMe
O
34
O
Me
HOMe N O
Bn
OOO
Me33
a) HClb) Me2C(OMe)2, CSA
c) LiOH71% Me
OMeHO
O
Me
MeMe
35
OMe
OMe
CO2H
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Gaich-‐Group Seminar Ruben Eckermann
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Kendomycin
H. J. Martin, T. Magauer, J. Mulzer, Angew. Chem. Int. Ed. 2010, 49, 5614 - 5626
Me
OMeO
O
Me
MeMe
36
OMe
OMe
EDCI, DMAP DMAP*HCl
hυ, 254 nm (cyclohexane)
41%
O
Me
OMe
O
Me
MeMe
37
OMe
HOO
O
Mea) NaBH4, HClb) TsOH
71%Me
OMe
O
Me
MeMe
38HO
O
HO
Me
Me
a) TESOTfb) IBX
61%Me
O
O
Me
MeMe
39O
O
TESO
Me
Me
aq. HF
50%
Me
O
O
Me
MeMe
kendomycin (40)
HO
O
HO
Me
Me
OH
20 18
Gaich-‐Group Seminar Ruben Eckermann
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Wittig rearrangement
[1,2] - rearrangement:
OH
EWG
X
X = I, Br, Cl, OTs, OMs
baseO
EWGn
nbase
O
EWG
n[1,2]
EWG
OHn
[2,3] - rearrangement:
OH
EWG
X
X = I, Br, Cl, OTs, OMs
baseO
EWGn
nbase
EWG OH
nO
EWG
n[2,3]
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Gaich-‐Group Seminar Ruben Eckermann
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Kallolide A ring system
HO
TBDPSO
Ph3PCO2Me
a) Swernb)
c) DIBAL-Hd) Swerne) CBr4, PPh3
63%
BrBr
Me
TBDPSO
a) BuLi, CH2Ob) mCPBA
62%
HO Me
TBDPSO
O a) Me2CuLi/LiAlH4 (THF), -78°Cb) TBSCl
52%
O
Me
CH
TBSO
Me
HO
TBDPSO
HO
TBDPSO
a) AgNO3, (ac)b) PPTS (ethanol)
79%
Ph3PCO2Me
a) Swernb)
c) DIBAL-Hd) DHPe) TBAF
O
Me
HO
MeTHPO
72%
a) TsClb) LiCCH, (DMSO)c) BuLi, CH2O
d) MsCl, lutidine then LiCle) PPTS, (EtOH)f) EtMgBr, (THF/HMPA)
52%
O
MeMe
O
41 42 43 44
45 46 47
J. A. Marshall, B. Yu, J. Org. Chem. 1994, 59, 324 - 331
Gaich-‐Group Seminar Ruben Eckermann
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Kallolide A ring system
J. A. Marshall, B. Yu, J. Org. Chem. 1994, 59, 324 - 331
O
MeMe
O
47
O
Me
OH
O
Okallolide A (53)
68%
BuLi, -78°C(THF/pentane)
O
Me
48
HOO
Me
49
HO+
7:3
a) Ac2Ob) MnO2
83%O
Me
50
AcO
MnO244%
O
Me
O
51
Me
E/Z = 2:3
53%
BuLi, -78°C(THF/pentane) O
Me
52
HO
15
15 12
12 12
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Gaich-‐Group Seminar Ruben Eckermann
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Stevens rearrangement
N
EWG
X
X = I, Br, Cl, OTs, OMs
baseN
EWGn
nbase
N
EWG
n[1,2]
EWG
Nn
[1,2] - rearrangement:
[2,3] - rearrangement:
N
EWG
X
X = I, Br, Cl, OTs, OMs
baseN
EWGn
nbase
EWG N
nN
EWG
n[2,3]
N
EWG
N2
n N
EWG
nRh2(OAc)4
via diazo-compound:
Gaich-‐Group Seminar Ruben Eckermann
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(±)-Desoxycodein-D
J.-P. Liou, C.-Y. Cheng, Tet. Lett. 2000, 41, 915 - 918
N
OAca) MeI, (CH2Cl2)b) NaBH4, (MeOH) 0°C
c) EtO2CCl, KHCO3 (ClCH2Ch2Cl), refluxd) NaOH, (MeOH), 0°C
73%
N
OH
CO2Et
CHO
MeO
BrHO
a) DEAD, PBu3, (THF)
b) NaBH4, (MeOH) 0°Cc) TBSCl, imidazoled) Pd(OAc)2, PPh3, NEt3 (MeCN), 130°C
45%
N
O
CO2Et
MeO
OTBS
a) TBAF, (THF)b) NCS, PPh3, (THF)
c) Pd(PPh3)4, NEt3 (MeCN), 130°C
54% N
O
MeO
MeI, (CH2Cl2)
N
O
MeO
Me
PhLi, (Et2O), 0°C
83%
N
O
MeO
Me
54 55
56
57
58 59 Desoxycodeine-D (60)
7 6
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Gaich-‐Group Seminar Ruben Eckermann
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Co - mediated O à C contraction
S. J. Meek, F. Pradaux, E. H. Demont, J. P. A. Harrity, Org. Lett. 2006, 8, 5597 - 5600
OR1
PPh3BF4
R2
R3O
a) nBuLi, -78°C (THF)
b) Co2(CO)8, (CH2Cl2)c) PPTS, (CH2Cl2)
OR1
R3
R2
3 eq. Et2AlCl(CH2Cl2) -78 to -30°C
OR3
R2LAR1
OR3
R2
R1
Co2(CO)6Co2(CO)6
(CO)6Co2
CAN, MeOH, 0°C
OR3
R2
R1
6
4
Gaich-‐Group Seminar Ruben Eckermann
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Co - mediated O à C contraction
Substrate scope:
O
Ph
O
TMS
O
OTBDPS
O
Bu
O
OTBDPS
OPh
OTBDPS
O
OTBDPS
OPh
TMS
O
TMS
O
Ph
O
TMS
O
OTBDPS
O
Ph Ph
O
O
TMS89% 84% 78% 86%
68% 71%78%
73%
75% 82%
49% 50% 49%80%
68%
61 62 63 64 65
66 67 68 69 70
71 72 73 74 75
S. J. Meek, F. Pradaux, E. H. Demont, J. P. A. Harrity, Org. Lett. 2006, 8, 5597 - 5600
01.10.14
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Gaich-‐Group Seminar Ruben Eckermann
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Zr - mediated O à C contraction
carbo-hydrate
O OMe
Cp2ZrCl2, nBuLiBF3*OEt2, (PhMe)-78 °C to rt
O OMe
ZrCp2
O
ZrCp2
OH
5
4
Gaich-‐Group Seminar Ruben Eckermann
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Zr - mediated O à C contraction
a) L. A. Paquette, X. Peng, J. Yang, Angew. Chem. Int. Ed. 2007, 46, 7817 – 7819 b) L. A. Paquette, G. D. Parker, T. Tei, S. Dong, J. Org. Chem. 2007, 72, 7125 – 7134 c) L. A. Paquette, R. M. Arbit, J.-A. Funel, S. Bolshakov, Synthesis 2002, 14, 2105 – 2109 d) J. D. White, S. Jana, J. Org. Chem. 2014, 79, 700 - 710
O
OH
HOHO
OHOH
D-glucose (76)
O OMe
OPMB
TBDPSOCp2Zr OH
OPMB
OTBDPS
60%
O
OMe
Me
Cp2Zr63%
HOMe
O OMe
OTBS
PMBO
OH
OTBS
PMBO
Cp2Zr
86%
7778
79
80
81
82
O OMe
MeMeBnO
Cp2Zr74%
OHMeMe
BnO
83 84
O
OH
O
O H
MeMe
MeH
MeMe OH Me
MeMe O
H H
OMe
OH
AcO
O
CO2Me OH
OAc
O
O
O
O
Providencin (85)
(+)-Epiafricanol (86)Pestalotiopsin A (87)
(+)-Fomannosin (88)
01.10.14
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Gaich-‐Group Seminar Ruben Eckermann
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One-carbon contraction
Gaich-‐Group Seminar Ruben Eckermann
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Wagner – Meerwein / Pinacol rearrangement
- rearrangement of cationic intermediates - mostly ring contraction / expansion sequence
Wagner – Meerwein rearrangement:
Pincaol rearrangement:
XMe Me
- X- - H+
n n n n
HOOTs
- OTs-
HOOH O
- H+
n n n n
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Gaich-‐Group Seminar Ruben Eckermann
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(±) - Bulnesol
J. A. Marshall, J. J. Partridge, Tetrahedron. 1969, 25, 2159 - 2192
EtO2C
O
OHHOa) H+
b) LiAlH4
c) MsCld) NaOPh (THF), reflux
OPh
O
O
a) H+
b) BF3*OEt2, (Et2O)CO2Et
N2
c) NaOEt O
d) H2SO4
O
H
CO2Et
PhO
a) OH-
b) LiAlH4 (DME), reflux
a) Li, NH3b) H3O+
c) Ac2O, py
HO
H
Me
PhO
d) MsCl, pye) H2, Pt Me
MsO
H
Me
AcO
HOAcNaOAc
MeH
a) CrO3b) CH2N2
c) NaOMed) MeLi
MeHMeMe OHOH
8990 91 92
93 94 (±) - Bulnesol (95)
65
c) TsCl, pyrd) LiAlH4 (DME), reflux
Gaich-‐Group Seminar Ruben Eckermann
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2-norCedrene
H. K. Hariprakasha, G. S. R. SubbaRao, Tet. Lett. 1997, 38, 5343 - 5346
MeO
NCCl a) KOH, 55°C
(DMSO/H2O)
b) BF3, MeOH (CH2Cl2)
78%
O
MeO
a) Pd/C, limoneneb) NaH, MeI, 60°C (DME)
c) NaBH4, 0°C (MeOH)
90%
HO
MeO
Me Me
BF3*OEt2(PhH), reflux
87%HMe Me
O a) MeLi, (Et2O) 0°C to reflux
b) POCl3, py, 0°C then HI, (PhH)
80%HMe Me
96 9798
99 2-norCedrene (100)
6
5
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Gaich-‐Group Seminar Ruben Eckermann
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Epoxide rearrangement
O OLA
CHOepoxidation LA
n nn
n
Gaich-‐Group Seminar Ruben Eckermann
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β – Microbiotene & Microbiotol
a) A. Srikrishna, S. A. Nagamani, J. Chem. Soc., Perkin Trans. 1. 1999, 3393 – 3394 b) A. Srikrishna, D. B. Ramachary, Tet. Lett. 1999, 40, 6669 - 6670
OMe Meβ - ionone (101)
a) NaOH, Br2 (dioxane), 0°C then H2SO4, (MeOH) reflux
b) mCPBA, NaHCO3 (CH2Cl2), 0°C
93%
O
Me
MeMeOMe
O
BF3*OEt2(CH2Cl2), -78°C
90% Me Me
Me
O
O
OMe
a) H2, Pd/C, (EtOH)
b) TiCl4, CH2Br2 Zn, (CH2Cl2), 0°C
60%
Me Me
MeO
OMe
a) NaOH, (THF/H2O) refluxb) (COCl)2, (PhH)
c) CH2N2, (Et2O), 0°Cd) Cu-CuSO4, (cC6H12) W-lamp, reflux
74%
Me Me
Me
OMe Me
Me
O
+
1 : 1.7
Ph3P+MeI-, NaOAm(PhH)
75% Me Me
MeMeMgI, (Et2O)
75%Me Me
Me
MeOH
102 102
104 105 106
106 106
β - Microbiotene (107) Microbiotol (108)
6 5
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Gaich-‐Group Seminar Ruben Eckermann
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Favorski rearrangement
OX
X = Cl, Br, I, OTs
baseO
Nuc-H
Nuc
O
n nn
Favorski rearrangement:
Homo-Favorski rearrangement:
O
X
X = Cl, Br, I, OTs
O Nuc
O
n n n
baseNuc-H
Gaich-‐Group Seminar Ruben Eckermann
30
ex (+) - Pulegone
L. F. Silva, Jr., Tetrahedron 2002, 58, 9137 - 9161
Me
O
a) Br2, (Et2O)
b) NaMeO, (MeOH)67%
CO2Me
Me
O
Me H
HO O
Me H
HO
Me
Me H
HO
MeMe
HMe
Me
Me
Me
MeO
O
(+) - Pulegone (109) 110
(-) - Mitsugashiwalactone (111)
(-) - Iridomyrmecin (112)
(+) - Epoxydictymene (113)
(+) - Acoradiene (114)
(-) - Acorone (115)
6 5
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Gaich-‐Group Seminar Ruben Eckermann
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Cubane
P. E. Eaton, T. W. Cole, Jr., J. Am. Chem. Soc. 1964, 86, 962 & 3157
O
a) NBS, (CCl4)b) Br2, 0°C (CH2Cl2/pentane)
c) Et2NH, (Et2O) -20°C
40%
OBr
Br
O
a) (CH2OH)2, pTSA (PhH), refluxb) HCl conc.
c) hυ, (PhH)85%
OBrO
O10% KOH
95% BrO
O
HO2C
a) SOCl2b) tBuOOH, py (Et2O)
c) 152°C, (cumene)d) 75% H2SO4
47%
Br
O 25% KOH
55%CO2H
a) SOCl2b) tBuOOH, py, (Et2O)
c) 150°C (diisopropylbenzene)
29%
116 117 118 119
120 121 Cubane (122)
Br
5 4
5 4
Gaich-‐Group Seminar Ruben Eckermann
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Oxidative contractions
Thallium (III) – promoted:
Lead (IV) – promoted: O OH
Pb(OAc)4 Pb(OAc)3HO
ROHHO OR
Pb(OAc)3CO2R
n n n n n- Pb(II)
Iodine (III) – promoted:
O OHTl(NO3)3 Tl(NO3)2
HOROH
HO ORTl(NO3)2
CO2R
n n n n n- Tl(I)
O OHHTIB I(Ph)OHHO
ROHHO OR
I(Ph)OHCO2R
n n n n n
IOH
OTsHTIB =
- PhI
L. F. Silva, Jr., Tetrahedron 2002, 58, 9137 - 9161
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Gaich-‐Group Seminar Ruben Eckermann
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Thallium (III) - promoted
a) V. M. T. Carneiro, H. M. C. Ferraz, T. O. Vieira, E. E. Ishikawa, L. F. Silva, Jr., J. Org. Chem. 2010, 75, 2877 – 2882 b) G. G. Bianco, H. M. C. Ferraz, A. M. Costa, L. V. Costa-Lotufo, C. Pessoa, M. O. de Moraes, M. G. Schrems, A. Pfaltz, L. F. Silva, Jr. J. Org. Chem. 2009, 74, 2561 – 2566 c) I. R. M. Tébéka, G. B. Longato, M. V. Craveiro, J. E. de Carvalho, A. L. T. G. Ruiz, L. F. Silva, Jr., Chem. Eur. J. 2012, 18, 16890 - 16901
Me
MeOMe Tl(NO3)3, (MeCN)
MS 3Å, 0°C
96%
MeO
Me
Me
CHO
a)PPh3
b) NaSEt, (DMF)56%
HO
Me
Me
NBoc
Me
Tl(NO3)3, (MeCN)then NaBH4
50% NBoc
MeHO
a) TsCl, py NEt3, (CH2Cl2)
b) NaBH4, (DMSO)70%
NBoc
Me
Me
123 124 (-) - Mutisianthol (125)
126 127 (+) - trans - Trikentrin A (128)
O
MeMe Tl(NO3)3, (MeOH)
TMOF, rt
59%
MeMe
MeO2C
a) H2, Pd/Cb) KOH, MeOH
c) MeLi86%
MeMe
O
HMDS, TMSIthen MeLithen CNCO2Me
64%
MeMe
MeO2C
O129 130 131 (+) - Bakkenolide A (132)
6 5
6 5
6 5
Gaich-‐Group Seminar Ruben Eckermann
34
Lead (IV) - promoted
L. F. Silva, Jr., Tetrahedron 2002, 58, 9137 - 9161
OMe
O MeO
O
13% 65%
54% 55%
Pb(OAc)4CH(OEt)3
HClO4
Pb(OAc)4CH(OEt)3
HClO4
Pb(OAc)4CH(OEt)3
HClO4
Pb(OAc)4CH(OEt)3
HClO4
CO2EtCO2Et
Me
CO2EtMe
CO2Et
129 130 131 132
133 134 135 136
5 4 6 5
7 6 8 7
O BF3*OEt2, (MeOH)then Pb(OAc)4, (PhMe)
43%
CO2Me
Bn Ph
HNO Ph
137 138 139
6 5
EtOO
Me
MeH
Me
O
Pb(OAc)4, BF3(PhH/EtOH)
80%O
Me
HMe
O
Me
EtO2C
140 141
6 5
01.10.14
18
Gaich-‐Group Seminar Ruben Eckermann
35
Iodine (III) - promoted
L. F. Silva, Jr., Tetrahedron 2002, 58, 9137 - 9161
O
Ar
nn = 1-3
PhI(OAc)2, CH(OEt)3HClO4
62 - 74%
CO2Et
Arn
O Ph
O
PhI(OAc)2, TMOF[H2SO4]
39%
OPh
CO2Me
142 143 144 145
6 5
Me
Me OH
HO
PhI)OAc)2, KOH(MeOH) then HCl
65%
Me
Me OH
H
MeO2C
146 147
6 5
PhIO*BF3(CH2Cl2), -15°C
60%CHO
O
PhIO*BF3(CH2Cl2), -15°C
36% OCHO
148 149
150 151
6 5
6 5
O
O
OHPhI(OAc)2(CH2Cl2), 0°C
91%
O
O
O
IPh
MeCN
reflux 55%
O
O
C OH2O
O
O
152 153 154 155
6 5
Gaich-‐Group Seminar Ruben Eckermann
36
(±) - Indatraline
L. F. Silva, Jr., F. A. Siqueira, E. C. Pedrozo, F. Y. M. Vieira, A. C. Doriguetto, Org. Lett. 2007, 9, 1433 - 1436
O
ClCl
a) NaBH4b) pTsOH
91%
ClCl
HTIBMeOH
62%
MeOOMe
Cl
Cl
a) Jones ox.b) SOCl2 then NH3
80%
NH2
Cl
Cl
O
PIFA
90%
NH2
Cl
Cl
a) Boc2Ob) NaH, MeI
c) MeOH, AcCl83%
NH*HCl
Cl
Cl
156 157 158 159
160 (±) - Indatraline (161)
65
01.10.14
19
Gaich-‐Group Seminar Ruben Eckermann
37
Wolff rearrangement
Odiazotransfer
n
O
n
N2 [M] or hυ
- N2
O
n
CO
NuH
ONu
n n
Gaich-‐Group Seminar Ruben Eckermann
38
(±) – Δ9(12) - Capnellene
M. Ihara, T. Suzuki, M. Katogi, N. Taniguchi, K. Fukumoto, J. Chem. Soc., Chem. Commun. 1991, 646 - 647
Me Me
O
a) CH2=CHMgBr, CuI (TMEDA) then CNCO2Me, HMPAb) HSCH2CH2SH, BF3*OEt2
c) cHex2BH then H2O2 NaOHd) Ra/Ni
73%
Me Me
CO2Me
OH
a) CSA, (PhH) refluxb) LDA, MeIc) DIBAL-H
d) Swerne) CH2=CHMgBrf) DMP
52%
Me Me O
O
H
Me
a) KOtBu, TBSCl (THF), -78°Cb) DBU
30%
Me Me OTBS
O
H
MeH
H
a) NaBH4b) TBAF
c) NaOMe, HCO2Etd) TsN3, NEt3
92%
Me Me O
HO
H
MeH
H
N2hυ, (MeOH)
48%
Me Me
HO
H
MeH
CO2Me
a) TBSOTf, DMAP 2,6-lutidineb) DIBAL-H
c) MsCl, NEt3d) o-NO2PhSeCN NaBH4 then H2O2
69%
Me Me
TBSO
H
MeH
H
a) TBAFb) NaH, CS2, imidazole then MeI
c) Bu3SnH, AIBN (PhMe)24%
Me MeH
MeH
H
162163 164
165 166 167
168 (±) - Δ9(12) - Capnellene (169)
H
6 5
01.10.14
20
Gaich-‐Group Seminar Ruben Eckermann
39
Salvilenone
R. L. Danheiser, A. L. Helgason, J. Am. Chem. Soc. 1994, 116, 9471 - 9479
O
Me
a) Br2, AlCl3b) Ph3P=CH2, (THF)
c) Tl(NO3)3, MeOH35%
BrO
Me
TrN3, KOH[Bu4NBr], 18-c-6(H2O/PhH)
88%
BrO
Me
N2
OSi(iPr)3
hυ (vycor)(ClCH2Ch2Cl)rt then 80°C
71%
Br
Me
CO
Br
Me
O OSi(iPr)3Br
Me
CO
OSi(iPr)3
Br
HO OSi(iPr)3
Me
a) MeLi, (THF) then nBuLi then acetone -78°C to rt then HCl, MeOH refluxb) TBAF, (THF)c) DDQ, (PhH)
43%Me
OO
170 171 172
173 174 175
176 Salvilenone (177)
7
6
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