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Mechanism for the rearrangement of Barton ester
Ph
O RR
O O N
S
P
O
OPhPhO
Ph
OP O
OPhPhO
Ph
Ph
R = CH2Ph
Ph Ph
Ph
O
P
O
OPhPhO
SSIP
Ph Ph
Ph
HO P
O
OPhPhO
Ph
OP
OPhPhOPh Ph
Ph
O
P
O
OPhPhO
CIP
Solvent
OP
O
OPhPhOPh Ph
Ph
+
Free ions
Ph
Ph
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-(Acyloxy)alkyl Rearrangement
OAcO
EtO CN+
O
EtO CN
OAc
O
EtO CN
H H
O
EtO CN
OAc
O
EtO CN
OAc
Surzur, J. -M.; Teissier, D. C. R. Acad. Sci. Fr. Ser. C.1967,
264, 1981.
Surzur, J. -M.; Teissier, D.Bull. Soc. Chim. Fr.
1970, 3060.
O
Ph
12
1'2'
3'O OO
Ph
OO
Ph
2,3-shift 1,2-shift
rearrangement
?
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Ar
O
O O N
S
P O
OPhPhO
Ar
OP
O
OPhPhO
Ar = 4-MeOC6H4
Ph
OP
O
OPhPhO
SSIP
Ar
HOP
O
OPhPhO
Ar
OP
OPhPhOAr
OP
O
OPhPhO
CIP
Solvent
OP
O
OPhPhO Ar+
Free ions
O
Mechanism for the rearrangement of Barton ester
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N
S
O
O
t-Bu OMe
OPO(OPh) 2
t-Bu OMe
OPO(OPh) 2 OPO(OPh) 2
MeO
t-Buh
MeO
t-BuArN
MeO
t-BuArN +
MeO
MeO
OAc
k239 x 106s
-1
(acetonitrile)
MeO
MeO
OAcH2O, H+
k20106s
-1
ESR observable
Detection of Radical Cations
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R d h i A li i i S h i
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OAcO
AcO
BrO
OAc
Ac
OAcO
AcO
OAc
OAc
OAcO
AcO
Br
OAcOAc
OAcO
AcO
OAc
OAc
OBzO
BzO
OAcO
AcO
BrO
OAc
(PhO) 2P
O
OAcO
AcO
O
OAc
(PhO) 2P
O
O
BnO
OMe
OBn
Bu3SnH, AIBN
benzene, reflux
92%
Bu3SnH, AIBN
benzene, reflux
TTMSS, AIBNbenzene, reflux
86%
HO
OBn
Bu3SnH, AIBNTHF, h Mg(ClO4)2
OAcO
AcO
OAc
O
OMeOBn
BnO
BnO
O
72%
/= 1/1
Rearrangements and their Applications in Synthesis
Br
OP(O)(OPh) 2
OBzO
BzO
OP(O)(OPh) 2
I t l l F ti f T t h d f
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Ph
O
O O N
S
PO
OPhPhO
Ph
OP
O
OPhPhO
Ph
OP
O
OPhPhO
CIP
PhO
O O
S
P
O
OPh
OPh
PhO P
O
OPh
OPh
?
OH
O
Ph
O
Ph
h
h
PhO
t-BuSH
R
Nu
R'R
X
R' R R'
NuNu Nu
ipso cine
Intermolecular Formation of a Tetrahydrofuran
i spoand cine Substitutions
80%
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ON
O
O
O
Ph
(PhO) 2P
O
O
O
Ph
(PhO) 2P
O
OH
O
Ph
(PhO) 2PO
OHPh
O(PhO) 2P
O
OPh OPh
Ph3Sn
Ph3SnH
Intramolecular Hydrogen Abstraction/cine Substitution
Sequence
95%
Eff t f S b tit t Yi ld
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ON
O
O
O
Ph
(EtO) 2P
O
OPh
ON
O
O
O
Ph
(EtO) 2P
O
OPh
ON
O
O
O
Ph
(EtO) 2P
O
OPh
PhSnH, AIBNbenzene, reflux
PhSnH, AIBN
benzene, reflux
PhSnH, AIBNbenzene, reflux
Effects of Substituents on Yield
60%
90%
90%
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Hoffmann-Loeffler-Freytag Reaction
NHRCl NHR
-Cl
NH2R
NHRCl
NH2R
ClNR
base
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Ph
O
NO2
P(OPh) 2
O
Ph
OP(OPh) 2
O
Ph
OP(OPh) 2
O
OH
PhO
OPh
Bu3SnH
Intermolecular Formation of a Tetrahydrofuran
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Cyclization Leading to a Lactone
Ph
OTHPNO2
CO2MePh
OTHP
NO2
CO2Me
Ph
OP(OPh) 2
NO2
CO2H
O
DBU, 80%
1. TsOH
2. (PhO)2POCl
O O
Ph
Bu3SnH
3. LiOH
A cine e o/e o Mode Tandem Cylization
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Ph
OTHP
NO2
OH
Ph
OTHP
NO2
NBoc
1. PPh3, I22.
NH2
3. Boc2O83%
1. TsOH2. (PhO)2POCl
Ph
OP(OPh) 2
NO2
NBoc
O
Ph
OP(OPh) 2
NO2
NH
O
TMSOTf
N
Ph
N
Ph
N N
Ph Ph
N
Ph
N
Ph
NN
Ph Ph
2.7 1.6 1 1
A cine-exo/exo-Mode Tandem Cylization
Transistion States of Formation of Products
Bu3SnH
85%
P S th i d i / M d T d C li ti
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O
OO
OH
NH
O
NBoc
NBoc
O
O2NP(OPh) 2
O
NH
O
O2NP(OPh) 2
O
NH2
1. LAH2. Boc2O
3. PCC
NO2Bu
tOK
TMSOTf
lutidine
Precusor Synthesis and a ipso exo/exo-Mode Tandem Cylization
Leading to Pyrrolizidine and Indolizidine Skeletons
N
HN
H
75%
Bu3SnH
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ipso endo/exo Mode Tandem
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ipso endo/exo-Mode Tandem
Cylization Leading to Bridged Systems
NO2
BnN
H
OP(OPh) 2
O
HN
Bn BnN
NO2HN
OP(OPh) 2
O
NBn
N N+
NO2
HN
OP(OPh) 2
O
n = 2
N
BnN
Bn
90%
78%17%
58%
ipso endo /exo dig Mode Tandem Cylizations
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ipso -endo /exo-dig-Mode Tandem Cylizations
NH
O2N
PhP(OPh) 2O
O N
HN
H
60%, E:Z= 5.7:1
Ph Ph
HN
O2N Ph
P(OPh) 2O
O
N
H
Ph
Formation of a Tetrahydropyran
Ph
NO2
OH
O P(OPh) 2
O
O
PhPh
OH
O
P(OPh) 2O
+AIBN
C6H
6/CH
3CN = 1/1
Bu3SnH
No cyclization
30%60%
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NO2
HN
OP(OPh) 2
O
n =1, 2
NH
OO2N
P(OPh) 2O
Conclusion
Nitrogen Containg
Heterocycles
Beckwith, A. L. J.; Crich, D.; Duggan, P. J.; Yau, Q. Chem. Rev.
1997, 97, 3273.Merph, J. A. In Radicals in Organic Synthesis;
Renaud, P., Sibi, M. P., Eds.; Wiley-VCH;Weinheim, 2001; Vol 1,
p298.Crich, D. In Radicals in Organic Synthesis; Renaud, P., Sibi,
M. P., Eds.; Wiley-VCH;Weinheim, 2001; Vol 2, p188.
References
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