tandem conjugate addition/ Ireland-Claisen rearrangment
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张张张 2001. 6. 11 tandem conjugate additio n/ Ireland-Claisen rearrang ment
description
tandem conjugate addition/ Ireland-Claisen rearrangment. 张文全 2001. 6. 11. Claisen rearrangement. Eschemoser-Claisen rearrangement. Johnson-Claisen rearrangement. Ireland-Claisen rearrangement. History first. Tseou, H.-F.; Wang, Y.-T. J. Chin. Chem. Soc. 1937, 5, 224. Other:. - PowerPoint PPT Presentation
Transcript of tandem conjugate addition/ Ireland-Claisen rearrangment
张文全2001. 6. 11
tandem conjugate addition/Ireland-Claisen rearrangment
O
R
O
R
O
R
R R'
OH NMe2
OMe MeO
R R'
OMeH
Me2N
H
R R'
O
NMe2
HB
R R'
O
NMe2
R R'
CONMe2
Claisen rearrangement
Eschemoser-Claisen rearrangement
R R'
OH
R R'
OR'H
R'O
H
R R'
O
OR'
HB
R R'
O
OR'
R R'
CO2R'
CH(OR')3H
Johnson-Claisen rearrangement
O
O
1)LDA
2) TMSCl
O
OSiMe3
O
OSiMe3
HCOOH
Ireland-Claisen rearrangement
O
O
Na0, 100oC
<10 yield%O
OHHistory first
Other:
Tseou, H.-F.; Wang, Y.-T. J. Chin. Chem. Soc. 1937, 5, 224
O
OPhPh
BrMg
ehterreflux, 30minrt, 40h
HO
OPhPh
74%
J. Am. Chem. Soc. 1949, 71, 1150
O
R
O NaHtoluenereflux
66-68%R=H or Me
O
R
OH
J. Org. Chem. 1960, 25, 1815
O
O Na0
toluenereflux
82%
O
OH
COOHchrysanthemic acid
Bull. Soc. Chim. Fr. 1964, 25, 2693
O
O
NaHtoluene, feflux24h
43%
O
OH
Synth. Commun. 1972, 2, 21
O
O
OEt
C5H11
1. LICATMSCl, THF-780C to rt
2. CH3SO3HEtOH
HO
O
OEt
C5H11
O
O
EtOC5H11
O
C5H11
dihydrojasmone
LICA ： lithium isopropylcyclohexylamide
Ireland. R. E. J. Am. Chem. Soc. 1972, 94, 5897
Methods of ketene acetal formation:
1. chemoselective deprotonation
O
ObaseTMSCl O
OH
2. electrochemical reduction
Tetrohedron. Lett. 1992, 33, 3847
O
ONEt4ClCH3CN
TMSCl, e-
reflux, 2h
O
OHO
OH
O
OO
O
TMS
TMS
3. Conjuate addition
O
O
Nu O
O
Nu O
O
Nu
SiR3
OH
O
Nu
tandem conjugate addition/ireland-Claisen rearrangment
O
O
R
O
OSiR''3
R
PR'3
R''3SiCl Base
O
OSiR''3
R
PR'3ClO
OSiR''3
R
PR'3Cl
C
PCy3(0.1eq)TESCl(3eq)DBU(2.5eq)CH3CN,500C
84yield%
J. Org. Chem. 1993,58, 299
Condition A: PCy3 (0.1 equiv), TESCl (3.0 equiv), DBU (2.6equiv), CHsCN, 50 oC, 24 h.
Condition B: PCy3 (0.05Sequiv), TMSCl(5.5 equiv), DBU (0.9 equiv), diisopropylethylamine (1.6 equiv),CH3CN, 80 OC, 24 h.
O
O
1.MeMgBr TMSClCuL2(1mol%)THF/ether-40oC,2h
2. 50oC, 3h 67%
COOH
7/3 ds
viaO
OTMS
Tetrahedron lett. 1990, 31, 7457
OCu
N
N
Ot-Bu
t-Bu
O
O
R2
R1RCu-780C O
OM
R2
R1
R
or R R2 or R2
R
claisen rearrr.t.
O
OM
R2
R1
R
H3O+
O
OH
R2
R1
R
Tetrahedron 1995, 51, 12631
OR'
O
RCu/LOR'
O
CuL
RTMSI
OR'
O
CuL
R
SiI
OR'
OSi
I
Cu
R
OR'
OSi
R
Cu
L
I
solvent: Et2O
O
O
1) MeCu(LiI)-TMSI,Et2O
2) -78oC(4h) then Et3NO
H
HOH
O
H
HOH
72%
erythro: threo=85:15
O
H
HOH
O
H
HOH
77%
erythro: threo=17:83
1) Me2CuLi-TMSCI,Et2O
2) -78oC(4h) then Et3N
Synlett. 1994, 271
More fast
O
O
O
O
R2Zn, TMSClCu cat.
Et2O, -78oCthen reflux
O
O
OH
R
O
Proposed Conjugate Addition/[3,3]-Rearrangement
O
O
O
O
R-MCu cat.
TMSCl
O
O
OSiMe3
O
R[3, 3]
O
O
OSiMe3
O
R
heat
TMSCl is need for high yield
OCu
N
N
Ot-Bu
t-BuJ. Org. Chem. 2008, 73, 1575
For different treament after rearrangement:
O
O
O
O
1) ZnEt2, Cu cat.Et2O, TMSCl-78oC, then reflux2) aq. HCl
O
OR
O
OH
O
O
O
O
1) ZnEt2, Cu cat.Et2O, TMSCl-78oC, then reflux
2) Me2SO4, K2CO3, acetone
O
O
CO2Me
R
R2
R1
R2
R1
R2
R1
R2 R1
O
O
O
O
1) ZnEt2, Cu cat.Et2O, TMSCl-78oC, then reflux
O
OR
O
O
Br
2) NBS, NaHCO3 CH2Cl2, 23oC
80%, d.r. 9:1
O
O
O
O
1) ZnEt2, Cu cat.Et2O, TMSCl-78oC, then reflux
O
OR
NH
2) (PhO)2P(O)N3, BnOH Et3N, CH2Cl2, reflux
67%
OBn
O
O
O
O
O
1) ZnEt2, Cu cat.Et2O, TMSCl-78oC, then reflux
O
OR
2) DCC, DMAP(S)-1-phenylethylamine CH2Cl2, 23oC 70%
O
HN Ph
F3C
R2
R3 R1
Ox
OLi THF, -78oCR3 O
R2
O CF
R1
Ox
Li F
F
Addition of palladium dichloridebenzonitrilecomplex at the rearrangement step wasfound to effectively suppress the unfavorable formation of the side products
J. Org. Chem. 1995,60, 8140
TMSCl O
R2
R3
OTMS
Ox
CF3
R1PdCl2(PhCN)2
reflux
O CF3
R1
O
Ox
R3
R2
O CF3
R1
O
Ox
R3
R2
Ox:O
O
O
O
R
i-PrI
Mncat. PbCl2THF, DMF
O
O
R
i-Pr OH
O
R
i-Pr
J. Org. Chem. 1996, 61, 8728
2 3
NNNMI:
iPrIO
O
nC5H11
Mn, cat. PbCl2Me3SiCl, NMI
THF/DMF(2/1)40oC, 1h
OH
O
Pri
nC5H11
O
O
R'
radical addotonfast
R-Ie
fast R
eslow
R
O
O
R'
R O
O
R'
R
O
O
R'
RMe3SiCl
O
OSiMe3
R'
R[3, 3]
ireland-claisenrearrangement
OSiMe3
O
R'
RH2O
OH
O
R'
Rtrap of anion
efast
R
O
R1
R2
Sit-Bu
t-Bu
AgOCOCF3(1-5 mol%)toluene
R
O
R1
R2
Sit-Bu t-Bu
O Si
RR1
R2
t-But-Bu
O
OSi
t-Bu
t-Bu
AgOCOCF3(1mol%)benzene
O Si
O
t-But-Bu
72%
O Sit-Bu
t-Bu
O
O
OSi
t-Bu
t-BuAgOCOCF3(1 mol%)benzene
72%
O Sit-Bu
t-Bu
O
RRO
O Sit-Bu
t-Bu
R
96%, 97:3 dr95%, one isomer
R=PhR=Me
J. AM. CHEM. SOC. 2005, 127, 2046
O
i-Pr O O Sit-Bu
t-Bu
Oi-Pr
O
OO
OAc(+)-5-epi-acetomycin
ORGANIC LETTERS 2007, 9, 1037
O
i-Pr O O Sit-Bu
t-Bu
Oi-Pr
Cu(OTf)2(5mol%)
97%
O
O R2R1 1. DABCO, TMSCl, DBU2. aq. HCl
75-90%
COOH
R1
R2
DABCO is more better than Et3N, i-Pr2NEt, DMAP, PPh3
Only DBU can reaction too
O
OH
R1
R2
H3O+
O
OTMS
R1
R2
NN O
O R2R1
O
O R2R1R3N
OOTMSR3N
O
OTMS
R1
R2H
NR3
TMSCl
[3, 3]-rearrangement
DBU
DBU-H+
SYNLETT 2007, No. 2, 0288Tetrahedron. 2007, 63, 9605
O
OBR2
H
MeMe
Z
-20oCthen H2O
HO
O
96%ee
NB
NArO2S SO2Ar
Ph Ph
Br
Me O
O
Me
Et3Ntoluene-hexane-78oC
i-Pr2NEtCH2Cl2-78oC
O
OBR2
Me
MeH
E
-20oCthen H2O
HO
O
>97%ee
Ar=
CF3
CF3
J. Am. Chem. SOC. 1991, 113,4026
thankyou for your attention
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