schroeder jacs 1999 - uni-konstanz.de
TRANSCRIPT
Literature Talk, Birte Schröder, 05.03.15, AK Gaich Group Seminar
1
1999
Some Fact about JACS1999
- Published articles: 2,166 - Pages: 12216 - Articles with „Total Synthesis“: 244
Most profilic authors: - Trost, B. M. (16) - Houk, K. N. (16) - Buchwald, S. L. (11) - Solomon, E. I. (10) - Whitesides, G. M. (10) - Rebek, J. (9) - Adam, W. (9) - Schuster, G. B. (8) - Boger, D. L. (8) - Danishefsky, S. J. (8)
Contribution by countries: - USA (1,355) - Japan (250) - Germany (144) - United Kingdom (119) - Canada (102)
3
4
Detailed Synthesis
N
N
O
OH
H
H
Ircinal A
NMe
N
O O
H
OMeMeO
Aspidophytine
HO
MeH
O
H
HN
Paniculatine
O
OH
OHAcO
O
H
H OMe
O
O
O
N NMe
Eleutherobin
NMe
O
O
O
MeO
O
Isostemofoline
NNH
NH
MeNHO
H
O
H
H
O
Br
Agelastatin
O
N2
O
OMeHO
O
O
OMe
OH insertion/[Claisen rearrangement
Methodologies
X
OMe
H
R'
R''X
R'
R''
[2 + 2]/Cope rearrangement
Key steps
N
O
O
OHOH
CO2HOH
MeO
Bu
Phomazarin
hetero Diels-Alder
N
HMe
OHOH
Allopumikiotoxin
Ni-cat. reductive cyclization
N NH
H
HAloperine
Intramolecular Diels-Alder
Sha Group: (+)-Paniculatine
∗∗ ∗∗
∗∗∗∗ ∗∗
HO ∗∗∗∗
MeH
O
H
HN
conjugate additionCu(I) mediated
radical cyclization
1,4 addition
amide formationcondensation
O
Me
SiMe2Ph
TMS (CH2)2 MgCl
OMe
OTBSMeNH2
- Structural Features: - Tetracyclic skeleton with an angularly fused tricyclic ketone - 7 stereocenters:
- 5 of them are consecutive - 1 quaternary stereocenter J. Am. Chem. Soc. 1999, 121, 866-867.
Tetrahedron Lett. 1995, 36, 351.5
- Key step: radical cyclization
O
Me
SiMe2Ph
TMS (CH2)2 MgCl1. CuI, TMSCl
2. NaI, mCPBA 67 %
O
Me
SiMe2PhI
HTMS
3. Bu3SnH, AIBNO
TMSSiMe2Ph
MeH
82 %
1
2
2
3
4
5
6 7
Sha Group: (+)-Paniculatine
O
Me
SiMe2PhI
HTMS
AIBN
OTMS
SiMe2Ph
MeH
O
Me
SiMe2Ph
HTMS
O TMS
SiMe2Ph
MeH
Bu3Sn HKey step:
6
Taber’s methodology:
R''
R'
SiLi, NH3 R''
R'
Si TBAF R''
R'
SiF
H2O2,KHCO3 R''
R'
OH
- Tamao-Flemming oxidation: activation of the phenyl group with e. g. KBr, BF3 * 2AcOH, HBF4 * OEt2
OTMS
SiMe2Ph
MeH
4. Li, NH35. TBAF
6. KHCO3, MeOH, H2O2 , 52%7. TBSCl, imid. 95%
HOTMS
OTBS
MeH
8. PCC, 90 %9. L-Selectride10. BnBr, KH, THF, 87 %
BnOTMS
OH
MeH
11. TFA, 82 %
BnOH
OTBS
MeH
12. SeO2, dioxane13. Swern, 62 %
O
6 8 9 7
7 10 11 12
13 14 15 16
Sha Group: (+)-Paniculatine
7
BnOH
OTBS
MeH
O
OMe
OTBS14.
LiClO4, Et2O, rt15. HOAc, H2O, THF 72 %16. Jones oxidation, 86 %
BnOHOOC
MeH
O
CO2MeH
17. (COCl)218. MeNH2, 81% BnO
MeH
O
H
NHOOMe
O
19. K2CO3, xylene reflux, 76%
BnO
MeH
O
H
HNO
O
H20. LiAlH4, THF21. Swern, 70 % HO
MeH
O
H
HN
ratio: α:β = 1:6
22. 10% Pd/C, H2
12 13 14
15 1
Kende Group: (+) Isostemofoline
NMe
O
O
O
MeO
O
OLiO
OMe
OHOH
O
HN
N
I
O OOTBS
N2
CO2MeIsostemofoline
Adol reaction
triple tandem cyclization
triple tandem cyclization
[4 + 3] cycloaddition
- Structural Features: - Pentacyclic core with a pendant conjugated butenolide
- Key Steps: - triple tandem cyclization - [4+3] cycloaddition
J. Am. Chem. Soc. 1999, 121,7431-32.
OHOH
1. 13% aq. NaOCl, HOAc, 65 %2. MOMCl, DiPEA, 93%
3. KOEt, 80%
HO
HN
N
OOMOM
NN
4. Na2S2O4, EtOH, H2O, 90°C, 35%
5. Boc2O, DMAP, MeCN, 72% N
Boc
OMOM6. Rhodium octanoate dimer, pentane, reflux, 90%
TBSO
N2
OMe
O
MeO2C
TBSONBoc
OMOM
8[4+3] cycloaddition
reductive cyclization
17
18
19
20
21
2223
20
22
24 25
19
26
Kende Group: (+) Isostemofoline
Key step: [4 + 3] cycloaddition
9
NBoc
OMOM rhodium octanoate dimer,pentane, reflux
NBoc
OMOM
MeO2C
TBSO
NBoc
OMOMMeO2C
TBSO
Cope rearrangement
MeO2C
TBSONBoc
OMOM
TBSO
N2
OMe
O
Claisen rearrangement
25
19
27 26
26 28 2930
31
7. TBAF, THF, 65%8. H2, Pd/C, MeOH, 90%9. H2O, DMSO, 150°C, 90% 10. furfural, NaOH, MeOH,
H2O, reflux, 90°CONBoc
MOMO
ONBoc
MOMO
O
11. LiHMDS, DMPU, THF, 0°C then allyl iodide, rt, 91% O
NBoc
MOMO
O
ONBoc
OMOM
O
+12. PhMe reflux 86 %
MeO2C
TBSONBoc
OMOM
Kende Group: (+) Isostemofoline
10
ONBoc
MOMO
O 13. K2OsO4, NaIO4, Et2O H2O, rt14. Zn(BH4)2, THF, -10°C, 52 %15. TIPSCl, imid., DMF, 93 % O
NBoc
MOMO
O OTIPS16. 2.2 equiv. MeLi, 1.1 equiv. DMPU, Et2O, -40°C, 85% O
NBoc
MOMO
OTIPSO17. TBAF, 90%18. TsCl, pyr. 90%19. O3, CH2Cl2, Me2S
ONBoc
MOMO
OTsCO2H
1,4 addition
triple tandem cyclization
20. i-BuOCOCl, NMM, THF, 0°C21. NaBH422. DMP
30 % over three stepsO
NBoc
MOMO
OTsCHO
23. THF, -78°C, 56%
OLiO
OMe
ONBoc
MOMO
OTsOHO
O24. DMP25. i) TFA ii) NaHCO3 (sat.) 67%
26. Tf2O, CH2Cl2
NMe
O
O
O
NMe
O
O
O
MeO
O
+
12 %
14%
MeO
ONBoc
-O
OTs
O
O
O
NMe
O
O
O
MeO
O
OH
Key step: triple tandem cyclization
32 33 34 35
36
18
37
38
17
39 40
Danishefsky Group: Eleutherobin
- Structural Features: - 10 stereogenic centers - urocanic ester linkage - arabinose domain - aglycon sector J. Am. Chem. Soc. 1999, 121, 6563-6579.
11
O
OH
OHAcO
O
H
H OMe
O
O
O
N NMeHO
O
NNMe
OCl
Cl
[2 + 2]
Stille
O O
O
OAcOBu3Sn
N
N
O
OBrBr
- Key Steps: - NHK ring closure - transposition of a pyranose to a furanose - novel oxacarbyglycosidation
OCl
Cl
1. trichloroacetyl chloride, Zn, Et2O, sonication, 0°C
H
H
ClCl
O
H
H
ClCl
O
minor major
65%
2. Zn, MeOH, NH4Cl, 87%3. t-BuOCH(NMe2)2, 60°C, 75%
H
H O
NMe2H
H O
4. pTSA, MeOH, 60°C, OMe
OMe
OMe
1 : 8
+
[2+2] cycloaddition
Bredereck reagent’s
41
42
43
44
45
46
47
43 44
48 49
50 51
Danishefsky Group: Eleutherobin
12
4. pTSA, acetone, 60% (o2s)
H
H O
O
OMeOBr
Br
5. nBuLi, THF, -78°C H
H O
HO
OMe OBr
H
H O
O
OBr
1.3 : 1
+
Triton B, THF, MeI
H
H O
OMe
OMe
OMe
6. TBDPSCl, imidazole, DMAP, 0°C, 97%
H
H O
OTBDPS
OMe OBr
7. i) DiBAl-H, > 95% ii) MsCl, pyr., DMAP, > 95% iii) KCN, 18c etther, MeCN, 80°C, 96%
8. DiBAl-H, 84%
H
H
OTBDPS
OBr
O
9. CrCl2 (5 equiv), NiCl2 (1 equiv) DMF, 74%
∗∗
O
OTBDPSH
HOH
15 : 1
NHK cyclization
52 53
46
54 55
56 57 58
Danishefsky Group: Eleutherobin
13
10. PivCl, DMAP, Et3N, CH2Cl2, 0°C, 91 %
11. TBAF, THFO
OHH
HOPiv
12. DMDO/acetone CH2Cl2, -78°C, 94%13. TMSOTf, 2,6-lutidine CH2Cl2, -78°C, 92%
H
HOPiv
O
OTMS
H14. MeLi (10 equiv), Et2O, -78°C, 86%
O
OTBDPSH
HOH
OH
HOPiv
O
OTMS
H OH
H
HOPiv
OMe
O
OH
15. cat. pTsOH*H2O MeOH, rt, 90%
H
HOPiv
O
OTMS
H OH
H
H
HOPiv
OR
HO OH
R=TMS, H, Me
16. TBSOTf, CH2Cl2, 2,6-lutidine, 0°C, 83%
H
HOPiv
OMe
O
OTBS
21. TBAF, THF, rt, 67%22. DCC, DMAP, CHCl3, 50°C, 50%
HO
O
NNMe
O
OH
OHAcO
O
H
H OMe
O
O
O
N NMe
23. PPTS, MeOH, heat 70%
H
H OMe
O
OTBS
OTf O
O
OAcO
O
20. Pd(PPh3)4 (cat.) LiCl (40 equiv) THF, 130°C, 40 - 50%
H
H OMe
O
OTBS
O O
O
OAcOBu3Sn
Eleutherobin
17. DiBAl-H, 88%18. TPAP, NMO, 87%
19. i) LHMDS, THF ii) Comins reagent
58 616059
62 63 64 65
66
48
67 42 41
Weinreb Group: Agelastatin A
N
NH
NH
MeNHO
H
O
H
H
O
Br
internalMichael addition
acylation
Sharpless/Kresze allylic amination
hetero Diels-Alder
addition to α - amino ketone
SO
NCO2Me
NSN
SES
SES
HN
TMS
ClOC
MeNCO
- Structural Features: - Tetracyclic alkaloid with four stereogenic centers
- Key steps: - hetero Diels-Alder reaction - Sharpless/Kresze allylic amination with a sulfodiimide
J. Am. Chem. Soc. 1999, 121, 9574-9579.
hetero Diels-Alder
[2,3] sigmatropic Mislow-Evans rearrangement 14
SO
NCO2Me
+ 1. PhH, 0°CS
NCO2Me
O
2. PhMgBr, THF, -60°C S
N
O
CO2MeH
PhN
CO2MeH OSPh
3. HMPT EtOH
80°CNH
O OH
H
OH
NHCO2Et
H
H(40%) (44%)
KOt-Bu
THF, 83%
68
71
70
69
7372
7069 74 75
76
77 78
Weinreb Group: Agelastatin A
Sharpless-Kresze allylic amination
15
SES = Si
Me
MeMe
SO
O
( ︎beta-trimethylsilylethanesulfonyl)
10. PDC, DMF 61 %
11. Cs2CO3, MeOH, 61%12. NBS, THF, 78%
NNH
O
O
HH
NHBocBr
13. TMSI, CH2Cl2, rt14. MeNCO, NaOH, H2O
NNH
O
O
HH
NHBr
OO
TMS 61%
NNH
NH
MeNHO
H
O
H
H
O
Br
Agelastatininternal conjugated addition
78 79 8081
8283
7372
84 85 86
NSN
SES
SES
PhMe, heat
NBoc
O OHS
H
NH
NTs
Ts[2,3]5.
4. Boc2O, DMAP, Et3N, 99%
NBoc
O OH
H
NSESSNHSES
NH
O OH
H
7. DMAP, Et3N, THF, 100 %
HN
TMSClOC
NBoc
O OH
H
SESN
NH
TMS
O
8. TBAF, THF, 66%9. LiOH, THF/H2O
NH
O OH
H
SESN
NH
TMS
O
NHBoc
OHH
H
HN
NH
TMS
O+
Boc2O, DMAP, 88%
(~ 1:4)
6. NaBH4
Corey Group: Aspidophytine
- Indole Alkaloid containing 4 stereogenic centers - two quaternary carbon centers
NMe
N
O O
H
OMeMeO
NO2
NO2
OMeOMe
OBr
MeO
O
NMeCNO2
TMSMgBr
Ac2O
Borchardt's modification
Vilsmeierformylation
Sakurai
Pictet-SprenglerIreland-Claisen
J. Am. Chem. Soc. 1999, 121, 6771-6772.
TMSO
Br
MeO
MgBr1.
CeCl3, THF, then H3O+, 83%
OBr
TMS
2. CBS reduction, 94 %3. 5% Na(Hg), MeOH, 23°C, 82%
4. Ac2O, Et3N, DMAP, CH2Cl2 , 97%
OAc
TMS
5. LDA, TBSCl, THF, -78°C, then heat
O
TMS
OTBSTMS
O
OHIreland-Claisen rearrangement
6. EDCI, i-PrOH, DMAP, CH2Cl2, 57% over 2 steps
TMS
O
OiPr
7. OsO4 (cat.), NMO, acetone-H2O, 57%8. NaIO4, THF-H2O 98%
TMS
O
OiPr
O O
16
87 88 89 90
91 92
93
89
93
94 95 96 97
98 99
Corey Group: Aspidophytine
Borchardt’s modification
NMe
OMeMeO
NH2
TMS
O
OiPr
O O
+
1. i) MeCN ii) TFAA iii) NaBH3CN 66% N
Me
N
O
OMeMeO
OiPr
TMS
NMe
N
O
OMeMeO
OiPr
TMS
NMe
N
H
O
H
OMeMeO
OiPr
NMe
N
H
O
H
OMeMeO
OiPr
H+Red.
NMe
N
H
O
H
OMeMeO
OiPr
Pictet-Sprengler reaction
aza-Sakurai reaction
17
NO2
NO2
OMeOMe
1. Fe, HOAc, silica gel PhMe, heat, 71%2. MeI, KOH, TBAI, THF, 94%
NMe
OMeMeO
3. POCl3, DMF aq. NaOH, 99%4. MeNO2, NH4OAc, heat, 92%
5. LiAlH4, THF, 88% NMe
OMeMeO
NH2
88 100 101
101 99 102 103
104105106
Corey Group: Aspidophytine
NMe
N
H
O
H
OMeMeO
OiPr2. NaOH, EtOH, 75°C, 88%3. K3Fe(CN)6, NaHCO3, tBuOH-H2O, 92%
NMe
N
O
H
OMeMeO
O
4. OsO4, DMAP tBuOH/H2O then NaSO35. Pb(OAc)4, AcOH CH2Cl2, -20°C
71% over two steps NMe
N
O
H
OMeMeO
O
6. KHMDS, THF, -78°C then PhNTf2, 54%7. Pd(PPh3)4, Bu3SnH, THF, 86%
NMe
N
O O
H
OMeMeO
O
18
106 107 108
87
Martin Group: Ircinal A
N
N
O
OH
H
H
HO NH2
O
NBoc
O
TBDPSO
CO2MeBr
PPh3
SnBu3
Li
RCM
RCM
O
Cl
N-acylation
1,2 addition
Diels-Alder
1,4 addition
Wittig
Stille
- Related to the Manzamine indol alkaloids - Structural features:
- 8-membered ring - 13-membered ring - tricyclic (6-6-5) core structure
- Key steps: domino-Stille/Diels-Alder reaction RCM reactions
J. Am. Chem. Soc. 1999, 121, 866-867.
HO NH2
1. Boc2O2. TBDPSCl
3. acrolein, H+
69%
TBDPSOBocN O
CO2MeBr
PPh3CH2Cl2, 90%
4.
5. TMSOTf, 2,6 - lutidine then pTsOH, 85%
TBDPSOH2N
Br
CO2Me
pTSO-
191,4 - addition
109
110
111
112
113
114
115
116
110 117
114
118
Martin Group: Ircinal A
20
SnBu3 BocNTBDPSO
NO
TBDPSO
CO2Me(PPh3)4PdPhMe, heat
N
NBoc
CO2Me
O
TBDPSO
H
OTBDPS
H 6. CrO3, 3,5 - Me2C3H2N263%
5. N
NBoc
CO2Me
O
TBDPSO
H
OTBDPS
HO
Stille coupling
Diels-Alder cascade
RCM for 13-membered ring
N
NBoc
CO2Me
O
TBDPSO
H
OTBDPS
HO
7. HCl, MeOH8. DMSO, (COCl)2, Et3N9. Ph3P=CH2, -78°C --> 0°C
47%
N
NBoc
CO2Me
O
H
HO
10. DiBAl-H11. DMP, 55% o2s12. MeOH, HC(OMe)3, H+
13. CH2=CHCH2CH2Li -78°C --> 20°C, 55%
N
N
H
H
OMeMeO
O
O
Ru=CHPhP(Cy)3
Cl
P(Cy)3Cl
67%
N
N
OMe
O
H
H
O
MeO14.
112 113 114
115
1. LiHMDS, CO2, -78°C2. NaBH4, O°C then H+
3. Na2CO3
"one pot"
NBoc
O
TBDPSO 95 %
NBoc
OH
TBDPSO
CO2Na
4. (COCl)2 (2.5 eq)then 118, Et3N
79 %
NBoc
TBDPSO
NO
TBDPSO
Br CO2Me
113
116 117
118 119 120 121
Martin Group: Ircinal A
21
N
N
OMe
O
H
H
O
MeO15. KOH, MeOH, heat16. O
Cl3 N
N
OMe
OH
H
H
MeO
O
17.
Ru=CHPhP(Cy)3
Cl
P(Cy)3Cl
75% then 1M HCl 26%
N
N
O
OH
H
H
18. DiBAl-H19. DMP, 56%
Ircinal ARCM for 8-membered ring
122 123 109
Key steps in Total Synthesis
JACS 1999
22
N
O
O
OHOH
CO2HOH
MeO
Bu
Phomazarin
N
HMe
OHOH
Allopumikiotoxin
N NH
H
HAloperine
Boger Group: Phormazarin
- Key step: Pyridine synthesis via an heteroaromatic azadiene Diels-Alder reaction
J. Am. Chem. Soc. 1999, 121, 2471-2477.
23
N
O
O
OHOH
CO2HOH
MeO
Bu
N
OMeOMe
CO2EtEtO2C
EtO2C
MOMOMeO
Bu
Li N
OMeOMe
CO2MeO
O
O
+
N
OMeOMe
CO2EtEtO2C
EtO2C
N
NN
CO2Et
EtO2C
EtO2COMe
MeO
OMe dioxane
100°C, 30minEt3N
+
N
N
N
CO2Et
EtO2C
EtO2C
OMe
OMe
OMe
Diels Alder
RetroDiels-Alder
N- N2
OMeMeO OMe
EtO2C
EtO2C CO2Et
H
Rearomatization
- Inverse electronic demand: - electron-deficient 1,2,4-triazine - electron-rich 1,1,2-trimethoxyethylene
124 125 126 127
128 129
130 131
127
Montgomery Group: (+)-Allopumiliotoxin
- Key step: Nickel catalyzed reductive cyclization of ynals
J. Am. Chem. Soc. 1999, 121, 6098-6099.
24
N
HMe
OHOH
N
HMe OH
O
N
HMe OH
O
N
O
BnOH R
NiLn
Et3SiH
Ni(COD)2PBu3
N
HMe
OTESOBn
N
O
BnOH
NiLn
R
N
OTES
BnOH
NiLn
R
Et3Si H
H
Et3SiH
132 133
133
134 135 136
137
Overman Group: (+)-Aloperine
- Key step: Intramolecular Diels-Alder reaction with a nitrogen-bound silicon tether J. Am. Chem. Soc. 1999, 121, 700-709.
25
N NH
H
H
NBoc
NTs
NBoc
NTs
TMSI, 2,6 -lutidineCH2Cl2, rt
MeOH, NaOH
NH
NTs
Me2OTfSi
O
OMe
Et3N, CH2Cl2, 0°C --> rt
N
NTs
Si
OMe
O
NSi N
TsHCO2Me
HH
H
NSi N
TsHCO2Me
HH
H
+
major minor
(5:1)
HF*pyridine, rt
then concetrate,mesitylene, reflux N N
H
H
H
SiMe2F
O
concentrate;
KF, KHCO3, H2O2,MeOH, THF, reflux
N NH
H
H
OH
O
N NH
H
H
OH
O
N NH
H
H
SiMe2F
O
+
63% 13%
oxidative cleavage
cleavage of N-Si bond
138 139
139 140 141
142 143 144 145+
146 147
Methodologies
JACS 1999
26
O
N2
O
OMeHO
O
O
OMe
OH insertion/[Claisen rearrangement
X
OMe
H
R'
R''X
R'
R''
[2 + 2]/Cope rearrangement
JACS 1999: Methodologies
27
1) Hoveyda-Grubbs Catalyst (1999): - exceptionally robust - can be purified by simple silica gel column - but also very expensive
Oi-Pr
N2
RuCl2(PPh3)3
CH2Cl2, -78°C
O Ru
Hα90%
PCy3 (2 equiv)
CH2Cl2, 75%
O Ru
Hα
Cl Cl Cl ClPPh3 PCy3
(1) Hoveyda, A. H. J. Am. Chem. Soc., 1999, 121, 791–799. (2) Fukuyama, T. J. Am. Chem. Soc., 1999, 121, 3791-3792. (3) Buchwald, S. L. J. Am. Chem. Soc., 1999, 121, 10252-10263.
2) Fukuyama Indole synthesis: Radical Cyclization of 2-Alkenylthioanilides to 2,3-disubstituted Indoles - under very mild radical conditions - has been applied to the total synthesis of aspidophytine, vinblastine and strychnine
3) Buchwald Indole synthesis: Palladium-catalyzed Preparation via Fischer Indole Synthesis - extends the Fischer-Indole Synthesis to broad variation of ketones - usually high yielding
R'
NH
R''S
SnBu3R'
NH
R''
S SnBu3
NH
HR'SSnBu3
R'' NH
R''
R'
Br+
R'R''
NH2N H
NN
R'R''
Pd(OAc)2,BINAP
NaOtBu, 100°C
Fischer Indole adduct
TsOH, EtOH
refluxR''' R''' N
H
R'
R''R'''
148 149 150
151 152 153 154
155 156 157 158
[2+2] Photocycloaddition/Thermal Retrocylcoaddition
28(1) M. L. Snapper J. Am. Chem. Soc. 1999, 121, 4534-4535.
A new entry into functionalized 5-8-5 Ring systems
- Cyclopentenones as versatile substrates - R’ = Me : only one regioisomer for the [2+2] - Inversion of stereochemistry at C-8
8 8
Proposed Mechanism:
X
hν
O
X
Me O
H
ΔOMe
H
R'
R''
X = C, OR' = Pr, CO2MeR'' = Me, OH
R'
R''159160
161 162
X
O
R'
R''H
Cope
X
O
R'
R''H
H Bond rotation
X
O
R'
R''
H
H
A' B' C'
O
X R''
R'
H
X
OMe
H
R'
R''O
X R''
H
X
OMe
H
R'
R''
R'
X
O
R'
R''H
Cope Bond rotation
A B C
X
O
R'
R''H
H
X
O
R'
HH
R''
H
HΔ
Δ
Cope
Cope
Rhodium Carbenoid-initiated Claisen Rearrangement
29(1) J. L. Wood J. Am. Chem. Soc. 1999, 121, 1748-1749.
Synthesis of alpha-Hydroxy Carbonyl Compounds- stereoselective formation of tertiary alcohols through a tandem O-H insertion/[3,3] rearrangement process - the observed intermediate is not the ketone whereas the (Z) enol ether is formed
164
163
165
166
167
OH
O
O OMe
O
Z - enol
Rh2(OAc)4, PhH,heat, 20min, 77%
O
O
O
OMeH
H[3,3]
HO
O
O
OMe
O
N2
O
OMe
163 168
164 169 168
O
N2
O
OMe
HO
Rh2L4O
Rh2L4
O
OMeO
O
O
OMe
H
L4Rh2
HO
O
OMe
O
O
O OMe
O
Z - enol
HHO
O
O
OMe
167
Revealed mechanism:
30
Thank you for your kind attention!