wu hua 2012.12.8
DESCRIPTION
Total Synthesis of Hirsutellone B and Enantioselective Synthesis of (-)-Acetylaranotin. Wu Hua 2012.12.8. Hirsutellones A–E. Masahiko Isaka. Tetrahedron , 2005 , 61 , 5577–5583. a. Isolated from the insect pathogenic fungus Hirsutella nivea BCC 2594. - PowerPoint PPT PresentationTRANSCRIPT
Wu Hua
2012.12.8
Total Synthesis of Hirsutellone B and Enantioselective Synthesis of (-)-Acetylaranotin
a. Isolated from the insect pathogenic fungus Hirsutella nivea BCC 2594. b. Structural features: a highly strained 12- or 13-membered ring containing a g-lactamor succinimide, a para-substituted phenyl ether, and a tricyclic polyketide moieties.
OH
Me
H
HH
O NH
O
OH
hirsutellone B
OH
Me
H
HH
O NH
O
hirsutellone A
H O
OH
Me
H
HH
O NH
O
OH
hirsutellone C
O
OH
Me
H
HH
O NH
O
hirsutellone D
H O
Me
OH
Me
H
HH
O NH
O
OH
hirsutellone E
Me
Hirsutellones A–E
Masahiko Isaka. Tetrahedron, 2005, 61, 5577–5583
K. C. Nicolaou. Angew. Chem. Int. Ed. 2009, 48, 6870-6874.
CHOMe
a) PPh3=CHIb) O3, Me2S CHO
Me
I
c) PPh3=CHCHO
NH
PhPh
OTMS
d)
, H2O2
then Ph3P=CHCO2Me
Me
I
OCO2Me
n-Bu3Sn TMS
CuTC (3.0 eq), NMPMe
OCO2Me
TMS
Et2AlCl (5.0 eq)CO2MeH
H
OHH
Me
pBrC6H4NCO (3.0 eq) CO2MeH
H
OH
Me
O
NH
Br
80% for two steps
58%
70% 50%
DMAP (3.1 eq), DCMr.t. 10h
100% H
(2.0 eq)
r.t. 6h DCM, r.t. 12h
OH
Me
H
HH
O NH
O
OH
hirsutellone B
a b c
de
R1
O
H
R2
H2O2, NH
PhPh
OTMS
DCM
R1
O
H
R2O
N
PhPh
OTMS
R2R1
OO H
R
NH
PhPh
OTMS
N
PhPh
OTMS
R2R1
OOR
N
PhPh
OTMS
R2R1
O
NH
PhPh
OTMS
H2O H2O
K. A. Jørgensen. J. Am. Chem. Soc. 2005, 127, 6964-6965
Asymmetric Organocatalytic Epoxidation of ,-Aldehydes with Hydrogen Peroxide
Copper-Mediated Cross-Coupling of Organostannanes with Organic Iodides at or below Room Temperature
L. S. Liebeskind. J. Am. Chem. Soc. 1996, 118, 2748-2749
S CO2Cu
CuTC
N
O
NMP
1-methylpyrrolidin-2-one(thiophene-2-
carbonyloxy)copper
CuTC, NMP
n-Bu3SnSnn-Bu3
1. n-BuLi, THF
2. ZnCl2 (1.1 eq)n-Bu3Sn
ZnCl
Pd(PPh3)4 (4.3 mol%)
THF, r.t. 1h
+ TMSI
n-Bu3Sn TMS (C18 reverse phase silica gel)
CuTC RCu
R-R'
R'RCuI
RSnBu3 TCSnBu3
R'I
RSnBu3 R'I+ R-R'
+ +
RCu +
R'RCuI + CuI
Me
OCO2Me
TMS
Et2AlCl
CO2MeH
H
OHH
MeDCM
Me
OCO2Me
TMS
AlEt2
Cl
H OAlEt2
CO2Me
H
Et2AlCl Et2AlCl
CAN: Ce(NH4)2(NO3)6
CO2MeH
H
OHH
Me
a) pTol4BiF, Cu(OAc)2 (cat.)b) LiAlH4c) PhI(OAc)2, TEMPO (cat.)
CHOH
H
OH
Me
Me
H H
BrMg OTBS
DMP
a)
b)
H
H
OH
Me
Me
H
O
OTBS
a) CAN (5.0 eq)b) NaBH(OAc)3
H
H
OH
Me H
O
OH
OH
ZnI2, AcSHH
H
OH
Me H
O
I
DCM, r.t.
68%
78% for three steps 91% for two steps
81% for two steps
SAc
a) NaOMe (1.4 eq)b) H2O2 (15 eq), Na2WO4 (1.0 eq)
THF/MeOH (1:1), r.t.H
H
OH
Me H
O
SO
O
79%
OH
Me
H
HH
O NH
O
OH
hirsutellone B
a b c
de
H
H
OH
Me H
O
OH
OH
ZnI2, AcSHH
H
OH
Me H
O
I
DCM, r.t.
68%
SAc
H
H
OH
Me H
O
OH
HSAc
H
H
OH
Me H
HO
SAc
OH
Zn(II)
H
H
OH
Me H
SAc
O
H2OZn(II)
H
H
OH
Me H
SAc
O
I
H
H
OH
Me H
SAc
OI
Mechanism
AD-mix-
H
H
OH
Me H
O
SO
O
a) KOH/Al2O3 (2g/mmol), CF2Br2 (5.0 eq)
b) LHMDS, NCCO2Me
DCM/t-BuOH (1:1)
THF61% for two steps
H
H
OH
Me H
OCO2Me
AD-mix-1.0 eq)H
H
OH
Me H
OCO2Me
MeSO2NH2 (1.7 eq)t-BuOH/H2O
OH
OH
r.t. 19h
90%
H
H
OH
Me H
OCO2Me
OHa) S=CCl2, DMAP, DCM, 1h
b) AIBN (2.0 eq), n-Bu3SnH (10 eq) toluene, 100 oC
65%
OH
Me
H
HH
O NH
O
OH
hirsutellone B
a b c
de
Ramberg-Bäcklund Reaction
T. L. Chan. J. Chem. Soc. Chem. Commum. 1994. 1771-1772
R S R'O O
H
OR''
R S R'O O
Br
F
F
Br
CF2Br
-Br
CF2..
R S R'O O
Br
base
R S R'O O
Br
R S R'O O
R''R R
R''+
-SO2
R S R'O O
R'
R+
R''R
KOH/Al2O3 , CF2Br2DCM/t-BuOH (1:1)
Barton Deoxygenation Reaction
R OHCl
S
R'O
S
R'R
Bu3SnHAIBN
R-H
AIBN C
CN
CN
H
Bu3Sn. .
Bu3Sn H
R .
R H
R OS
R'R OHBu3Sn S
O
R'
N NN N
AIBN
D. H. R. Barton. J. Chem. Soc., Perkin. Trans. 1. 1975, 16, 1574-1585
H
H
OH
Me H
OCO2Me
OH
DMP (2.0 eq)H
H
OH
Me H
OCO2Me
O
NH3
H
H
OH
Me H
OCONH2
O
OH
Me
H
HH
O NH
O
OH
hirsutellone B
MeOH/H2O120 oC
DCM, r.t., 2h 92%
50%
H
H
OH
Me H
OCONH2
O
Amidation
Epimerization
Cyclization
S. E. Reisman. J. Am. Chem. Soc. 2012, 134, 1930–1933
N
O
N
O
HOH
HHO
O
O
N
O
HTeoc
CO2Et
TBSO
metal-catalyzed cycloisomerization
NH
Teoc
CO2Et
TBSO
HO
H
NH
Teoc
CO2Et
HO
O
Ph
catalytic asymmetric (1,3)-dipolar cycloaddition
OO
O
H
Ph NH2
CO2Et
commercially available starting materials
N
O
N
O
HOAc
HAcO
O
S S
O
acetylaranotin
Enantioselective Total Synthesis of (-)-Acetylaranotin
[医 ]乙酰珠囊壳素
N
O
OO
O
OSi
Teoc-OSu
O N
O CuO
N OMe
R
HO
t-BuO
H. Y. Kim, H. J. Shih, W. E. Knabe, K. Oh. Angew. Chem., Int. Ed. 2009, 48, 7420.
t-BuO2C
+
N CO2Et
1. CuI (10 mol%) brucin-OL (10 mol%) DBU (10 mol%) (50% yield)
2. TFA, Et3SiH DCM (77% yield)
NH
HOOC
CO2EtPh
> 98% ee
1. Teoc-OSu, Et3N H2O/dioxane (83% yield)
2. O3, DCM, -78 oC then DMS (93% yield)
N
O
O
HOTeoc
H
HCO2Et
MgBr
THF, -78 oC to 0 oC
then PPh3, DIADDCM, 0 oC(76% yield)
N
O
O
Teoc
H
HCO2Et
NaBH4, EtOH
(86% yield) N
Teoc
H
HCO2Et
HO
HO1. TBSOTf, 2,6-Iutidine DCM, 0 oC (85% yield)
2. AcOH, THF, H2O (3:1:1) (79% yield)
N
Teoc
H
HCO2Et
TBSO
HO
N
Teoc
Cl
HCO2Et
TBSO
HO1. DMP, pyr, DCM (93% yield)
2. NCS, DCM pyrrolidine. TFA NaBH4, EtOH (93% yield)
N
O
O
HOTeoc
H
HCO2Et
MgBr
THF, -78 oC to 0 oC
then PPh3, DIADDCM, 0 oC(76% yield)
N
O
O
Teoc
H
HCO2Et
N
O
O
HOTeoc
H
HCO2Et
MgBrTHF, -78 oC to 0 oC
N
O
O
Teoc
H
HCO2Et N
O
O
Teoc
H
HCO2Et
+
69% 13%
N
O
O
HOTeoc
H
HCO2Et
MgBrTHF, -78 oC to 0 oC
N
O
Teoc
H
HCO2Et
HO
HO then PPh3, DIADDCM, 0 oC T.M.
N NEtO2C
CO2EtPh3P
N NEtO2C
CO2EtPh3P
O
R'OH
N NEtO2C
CO2EtPh3P
H
R O
N NEtO2C
CO2EtPh3P
HR O
H
Ph3P NN
CO2Et
CO2Et
HR O PPh3 N N
EtO2C
CO2EtH
H+
R O PPh3
+R'
O
O
R'
O
O
Ph3P O
R'
O
OR
H
Mitsunobu Reaction
N
Cl
Teoc
HO
CO2Et
TBSO
[Rh(cod)Cl]2 (5 mol%)(4-FC6H4)3P (60 mol%)
DMF, 85 oC(88% yield)
N
Cl
Teoc
CO2Et
O
H HTBSO
LiCl, Li2CO3
DMF, 100 oC
(53% yield) N
Teoc
CO2Et
O
HTBSO
Me3SnOHDCE, 80 oC(90% yield)
N
Teoc
CO2H
O
HTBSO
1. TBAF, THF, 0 oC (84% yield)2. LiCl, Li2CO3, DMF, 100 oC (65% yield)
NH
CO2Et
O
HTBSO
+BOP-ClEt3N, DMF
(87% yield)
N CO2Et
O
HTBSO
O N
O
Teoc
HH
OTBS
ON P
O
N
Cl
O
OO
BOPCl
Rhodium-Catalyzed Cycloisomerization: Formation of Indoles, Benzofurans, and Enol Lactones
NH2
R
[Rh(cod)Cl]2 (5 mol%)
(4-FC6H4)3P (60 mol%)NH
R
DMF, 85 oC
1/2 [Rh(cod)Cl]2 + 2Ph3P
PPh3
RhPh3P Cl NH2
R
NH2
R RhLn
NR
H H
RhLn
NH
R RhLn
H
NH
R
B. M. Trost. Angew. Chemie. Int. Ed. 2007, 46, 2074-2077
N CO2Et
O
HTBSO
O N
O
Teoc
HH
OTBS
TBAF.(t-BuOH)4
MeCN, 70 oCN2 atm(76% yield)
N
O
N
O
HOAc
HAcO
O
S S
O
N
O
N
O
HOH
HHO
O
OH
H
TBAF.(t-BuOH)4
CD3CN, 70 oCAir (50% yield)
N
O
N
O
HOH
HHO
O
O
S
SS
S
1. AcCl, DMAP DCM (70% yield)2. HSC3H6SH (100 eq) Et3N, MeCN; then O2 (45% yield)
18 steps from ethyl glycinate
NaHMDS, THFS8, NaHMDSthen NaHMDS
(40% yield)
TBAF.(t-BuOH)4
MeCN, 70 oCAir atm(27% yield)
N
O
N
O
HOH
HHO
O
OOH
HO
0.96 mg