Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three...
Transcript of Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three...
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Ring Expansion/Contraction ReactionsLecture Notes
General Reviews:L. F. Silva, Tetrahedron 2002, 58, 9137.
Wagner-Meerwein Rearrangements/Carbocations:X. Criery, Chem. Rev. 1991, 91, 1625.
Grob Fragmentations:C. A. Grob, P. W. Schiess, Angew. Chem. Int. Ed. 1967, 6, 1.
Pinacol Rearrangements:Z.-L. Song, C.-A. Fan, Y.-Q. Tu, Chem. Rev. 2011, 111, 7523.
Wolff Rearrangements:W. Kirmse, Eur. J. Org. Chem. 2002, 2193
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Ring Contractions/Expansions: Why Bother?
D. L. Boger, C. M. Baldino, J. Am. Chem. Soc. 1993, 115, 11418.
N N
NN
CO2MeCO2Me
MeOMeO
MeO2C
MeO2C
NH
NH
CO2MeMeOMeO
CO2Me
CO2Me
MeO2C
-[NH3](68%)
HN N
NNH
CO2MeCO2Me
MeOMeO
MeO2C
MeO2C
H2N NH
NHNH2
CO2MeCO2Me
MeOMeO
MeO2C
MeO2C
N
N
CO2HMeOMeO
CO2H
CO2H
HO2C
NaH, MeI, DMF
Me
MeN
N
CO2MeMeOMeO
CO2Me
CO2Me
MeO2C
Me
Me
(100%)LiOH
Reductivecleavage
Zn,HOAc
Enamine-Iminecondensation
(98%)
22 °C,24 h
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Electrocyclization Cascades:Black's Hypothesis for the Biosynthesis of the Endiandric Acids
OO
OMeMe
OPMB
XX
OTBS
D. St. C. Black and co-workers, Aust. J. Chem. 1982, 35, 2247.
CO2H
HO2C
Ph
CO2H
PhCO2H
Ph
Ph
HO2CPh
HH
H
CO2H
HH
HPh
endiandric acid D
endiandric acid E
Diels-Alderreaction
A = conrotatory 8πelectrocyclization
B = disrotatory 6πelectrocyclization
A
A
B
B
HH
PhH
HH
endiandric acid A
CO2H
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4π-Electrocyclic Reactions:Part of a Total Synthesis of Periplanone B
OO
OMeMe
OPMB
XX
OTBS
S. L. Schreiber, C. Santini, J. Am. Chem. Soc. 1984, 106, 4038.For a review, see: Classics in Total Synthesis I, Chapter 21
OH
Me
Me
OH
Me
Me
O
Me
Me
H
Me
Me
175 °C, toluene
O
Me
Me
hν
O
Me
Me
O
O
O
periplanone B
Oxy-Coperearrangement
4π-conrotatoryelectrocyclicring opening
KH,18-Crown-6
OO
OO
O
O
18-crown-6
(75%)
(82%)
Olefin isomerization
+
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6π-Electrocyclic Reactions:Erasure of the Ring-Opened Product
OO
OMeMe
OPMB
XX
OTBS
E. J. Corey, A. G. Hortmann, J. Am. Chem. Soc. 1965, 87, 5736.
OO
MeMe
Me
dihydrocostunolide
H
OO
MeMe
H
Me
HO
Br
OO
MeMe
H
Me
HOO
O
MeMe
H
Me
HHO
OO
MeMe
H
Me
HOO
MeMe
Me H hν, MeOH,-18 °C
Al(Oi-Pr)3,i-PrOH, Δ
Al2O3,pyridine,
220 °C
LiBr,DMF,
120 °C
What is the name reaction in the second step?
H2,Raney NiMeOH,-18 °C
6π-conrotatoryelectrocyclicring opening
25 °C
OO
MeMe
H
Me
H
6π-disrotatoryelectrocyclization
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6π-Electrocyclic Reactions:One of Three Pericyclic Reactions in a Colchicine Total Synthesis
OO
OMeMe
OPMB
XX
OTBS
A. Eschenmoser and co-workers, Helv. Chim. Acta 1961, 44, 540.
O
O
MeO
MeOMeO
O
O
O
Cl
Diels-Alderreaction
MeO
MeOMeO
OH
O
O
Cl
O O
MeO
MeOMeO
OH
O
O
Cl
MeO
MeOMeO
CO2Me
CO2Me
H
ClMeO
MeOMeO
CO2Me
CO2Me
norcaradiene derivative
MeO
MeOMeO
CO2Me
CO2Me
colchicine
RetroDiels-Alder
reaction
-[CO2]
t-BuOK
1. MeOH, H2SO42. CH2N2
6π-disrotatory electrocyclic ring openings are often referred to as norcaradiene rearrangements
6π-dis-
rotatoryopening
25 °C
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Oxidative Ring Expansions
P. A. Wender and co-workers, J. Am. Chem. Soc. 1997, 119, 12976.
OH
Me
OAc
OBn
OOTBS
OOOAc
OTBS
Me
OAc
OBn
OOOH
OTBS
Me
OAc
OBn
OH
Me
OAc
OBn
OOTBS
OOH
Me
OAc
OBn
OOTBS
OH
O
Me
OAc
OBn
OOH
OTBS
mCPBA,THF,
0→25 °C,12 h
Ac2O,4-DMAP,
(96%)
py, 0 °C,10 min
[Ketalization](100%)
-[H ]
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Ring Contractions/Expansions: Why Bother?
K. Iida and co-workers, FEBS 2007, 274, 3475.
NH HN
NNH
MeCO2H
CO2Me
CO2H
CO2MeMeO2C
HO2CMe
MeHO2C
MeO2C
precorrin core
NH N
NN
MeCONH2
CONH2
Me
CONH2RHNOC
H2NOC
MeH2NOC
H2NOC
Me
Me
H
MeMe
Me
vitamin B12
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Ring Contractions/Expansions: Why Bother?
T. Narender and co-workers, J. Nat. Prod. 2010, 73, 747.
BzOH OAcO
OHAcOMe
O
O
NH
O
Ph
Ph
OH
O
HOTaxolTM
H
OAcAcOMe
AcO
AcO
HOAc
H
OAcAcOMe
AcO
HOAc
H
OAcAcOMe
AcO
OAcH
BF3•OEt2
(70%)
abeotaxane frameworktaxane framework
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Progesterone: A Critical Steroid
Me
HMe
OH H
OMeH
progesterone
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Progesterone: A Critical Steroid
Me
HMe
OH H
OMe
H
progesterone
Me OH
Me
MeMe
MeMe
Me
MeO O
O
ClClTFA, 0 °C
Me
HMe
H H
OMe
H
Me
(72%)
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Progesterone: A Critical Steroid
Me
HMe
OH H
OMe
H
progesterone
Me OH
Me
MeMe
MeMe
Me
MeO O
O
ClClTFA, 0 °C
Me
HMe
H H
OMe
H
Me
(72%)
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Drugs of the Future?
with A. P. Brucks, D. S. Treitler, I. Moga, J. Am. Chem. Soc. 2012, 134, 17714.
NHNNH
NH2 HN
NHNH2N
•H2SO4
Octaporphyrin[30 electron system, n = 7]
O
HNH
H
HOH H
H
Cyclopamine
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Drugs of the Future?
with A. P. Brucks, D. S. Treitler, I. Moga, J. Am. Chem. Soc. 2012, 134, 17714.
NHNNH
NH2 HN
NHNH2N
•H2SO4
Octaporphyrin[30 electron system, n = 7]
O
HNH
H
HOH H
H
Cyclopamine
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Ring Contractions/Expansions: Why Bother?
A. Giannis and co-workers, J. Am. Chem. Soc. 2010, 132, 9968.
OH
HO O
HHBnO
N
NTf Tf
Cl
O
O
HBnO
O
O
HBnO
H
H
+
74% 22%
HO
H
O
H HMeO
H
O
H HMeO
N
NTf Tf
Cl
HMeO
H H
O
HH
39% 41%
+
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Ring Contractions/Expansions: Why Bother?
A. Giannis and co-workers, J. Am. Chem. Soc. 2010, 132, 9968.
OH
HO O
HHBnO
N
NTf Tf
Cl
O
O
HBnO
O
O
HBnO
H
H
+
74% 22%
HO
H
O
H HMeO
H
O
H HMeO
N
NTf Tf
Cl
HMeO
H H
O
HH
39% 41%
+
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Ring Contractions/Expansions: Why Bother?
H.-G. Schmalz and co-workers, Org. Lett. 2012, 14, 3692.
O
H
AcO
H
H
OH
O
H
AcO
H
H
O
H
AcO
H
H
OMe
What other productscould have formed?
BF3•OEt2
MeOH,CH2Cl2
(93%)
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Ring Contractions/Expansions: Why Bother?
E. M. Carreira and co-workers, J. Am. Chem. Soc. 2002, 124, 14826.
NH
N
MeNHNO
H HHO
strychnofoline
NH
OBnO
MgI2
NH
OBnO
IN OTBDPS
NH
N
OH H
OTBDPS
BnO(55%)
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Wagner-Meerwein Rearrangements
E. M. Carreira and co-workers, J. Am. Chem. Soc. 2002, 124, 14826.
OH[1,2-alkyl
shift]
OCHOO
Can you devisea mechanism
for the openingoperations?
(51%)
45 oC
HCO2H
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O
O
Wagner-Meerwein Rearrangements
A. B. Smith and co-workers, J. Org. Chem. 1984, 49, 4094.
O
THF,50 oC
H2SO4
OHO
OHO
OOO
O
quadrone
[1,2-alkylshift]
(85%)
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Pinacol Rearrangements for Ring Contractions and Expansions
P. G. Harran and co-workers, Angew. Chem. Int. Ed. 2001, 40, 4765.
H2SO4
conc.H2SO4
40%H2SO4
Ph
OPh
PhH
O
Ph
PhPh
OHHO O
Original discovery [R. Fittig, 1860]
Controlling product distribution [S. Danilov, 1917]
OHHO
PhPh
HPh
Key mechanistic consideration: diol/epoxide equilibrium
OHHO
RR
RR
OH
RR
RR
R
OR
RR
RR
RR
O
protic acid or Lewis acid conditions
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Pinacol Rearrangements for Ring Contractions and Expansions
P. G. Harran and co-workers, Angew. Chem. Int. Ed. 2001, 40, 4765.
H2SO4
conc.H2SO4
40%H2SO4
Ph
OPh
PhH
O
Ph
PhPh
OHHO O
Original discovery [R. Fittig, 1860]
Controlling product distribution [S. Danilov, 1917]
OHHO
PhPh
HPh
Key mechanistic consideration: diol/epoxide equilibrium
OHHO
RR
RR
OH
RR
RR
R
OR
RR
RR
RR
O
protic acid or Lewis acid conditions
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Pinacol Rearrangements for Ring Contractions and Expansions
P. G. Harran and co-workers, Angew. Chem. Int. Ed. 2001, 40, 4765.
OHOHOH
OH
OHOHOHOH
O
O(93%) (7%)
O
O(97%) (3%)
aq.HClO4
aq.HClO4
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Pinacol Rearrangements for Ring Contractions and Expansions
P. G. Harran and co-workers, Angew. Chem. Int. Ed. 2001, 40, 4765.
OHOHOH
OH
OHOHOHOH
O
O(93%) (7%)
O
O(97%) (3%)
aq.HClO4
aq.HClO4
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Pinacol Rearrangements for Ring Contraction
P. G. Harran and co-workers, Angew. Chem. Int. Ed. 2001, 40, 4765.
originally proposed structure of diazonamide AHO
O
N
MeMe
ON
ON Cl
NH
Cl
OOH
NH2N
Me Me
O
H H
revised structure of diazonamide A
O
O
N
MeMe
ON
ON Cl
NH
Cl
NH
N
Me Me
O
H H
HO
+
BnO
O
N
MeMe
ON
O
CBzHNH
BrO
Br
CN
BnO
O
N
MeMe
ONBocHN
H
BrO
Br
CN
OHOH
H
HOBnO
OH2ArO
Br
Br+1. p-TsOH
(3.0 equiv), toluene, 95 oC, 40 min2. N-(benzyloxy- carbonyloxy)- succinimide
(54%overall)
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Pinacol Rearrangements for Ring Expansion
P. S. Baran and co-workers, Science 2013, 341, 878.
OTMS
Me
MeMeHO
OOO Me
OTBSH
Me
Me
Me
Me
H
Me
OHMe
H
Me
MeH
Me
OHMe
HOO
OHOH
OH phorbol
Me
HOHOOH
O
MeMeMe
H
HO ingenol putative intermediate
BF3•OEt2(10 equiv),
CH2Cl2-78 oC to
-40 oC, 30 min(80%)
Me
HOHOOH
O
MeMeMe
H
HO ingenol
Me
Me
O
MeMeMe
H
OTBSOOO
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Pinacol Rearrangements for Ring Expansion
P. S. Baran and co-workers, Science 2013, 341, 878.
OTMS
Me
MeMeHO
OOO Me
OTBSH
Me
Me
Me
Me
H
Me
OHMe
H
Me
MeH
Me
OHMe
HOO
OHOH
OH phorbol
Me
HOHOOH
O
MeMeMe
H
HO ingenol putative intermediate
BF3•OEt2(10 equiv),
CH2Cl2-78 oC to
-40 oC, 30 min(80%)
Me
HOHOOH
O
MeMeMe
H
HO ingenol
Me
Me
O
MeMeMe
H
OTBSOOO
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Semi-Pinacol Rearrangements for Ring Contractions and Expansions
P. G. Harran and co-workers, Angew. Chem. Int. Ed. 2001, 40, 4765.
R RHO RM
XX = OMs, OTs, Cl, Br, I,
N2+, SR, SeR, etc.
Bronsted acid or baseR R
O
RM
RR2
R1
O RM
X
H
nO σ*C-C (app)σC-C σ*C-X (app)
R
HO RMR
O
R RM
R
E RE
RR
R
R
ORM
RR
REH
Electrophiles for intramolecular cases:oxocarbeniums, thiocabeniums, iminiums
Electrophiles for intermolecular cases:haloniums, seleniums, proton, Lewis acids
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Pinacol Rearrangements for Ring Expansion/Contraction
J. K. Cha and co-workers, Angew. Chem. Int. Ed. 2005, 44, 121.Tanino and co-workers, J. Am. Chem. Soc. 2003, 125, 1498.
AlMe3,CH2Cl2
-78 to 0 oC
MeH
H
OAl
H
OH
H
(82%)89
10
114
8910
11
4
H
O
MeMeMe
HHOMe
MeH
Me
OH
HO
O
AlMe3,CH2Cl2
(76%over
2 steps)
HMe
O
H HOR
OH
OMe
AlR = TIPS
MeO
O
MeMeMe
HHO
OTIPS
MeMeMe
HOH
OTIPS
O
OMe
![Page 30: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/30.jpg)
Pinacol Rearrangements for Ring Expansion/Contraction
J. K. Cha and co-workers, Angew. Chem. Int. Ed. 2005, 44, 121.Tanino and co-workers, J. Am. Chem. Soc. 2003, 125, 1498.
AlMe3,CH2Cl2
-78 to 0 oC
MeH
H
OAl
H
OH
H
(82%)89
10
114
8910
11
4
H
O
MeMeMe
HHOMe
MeH
Me
OH
HO
O
AlMe3,CH2Cl2
(76%over
2 steps)
HMe
O
H HOR
OH
OMe
AlR = TIPS
MeO
O
MeMeMe
HHO
OTIPS
MeMeMe
HOH
OTIPS
O
OMe
![Page 31: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/31.jpg)
Pinacol Rearrangements for Ring Expansion
J. S. Kingsbury and E. J. Corey, J. Am. Chem. Soc. 2005, 127, 13813.
HO
OMTM
O
O
AlMe3,toluene,CH2Cl2,
4 oC(90%)
O
O
OOO
O
OCH2SMe
AlHMe3
OHH
β-araneosene
OHOH
MsCl,CH2Cl2,
-30 to 4 oC
(98%)
![Page 32: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/32.jpg)
Pinacol Rearrangements for Ring Expansion
J. S. Kingsbury and E. J. Corey, J. Am. Chem. Soc. 2005, 127, 13813.
HO
OMTM
O
O
AlMe3,toluene,CH2Cl2,
4 oC(90%)
O
O
OOO
O
OCH2SMe
AlHMe3
OHH
β-araneosene
OHOH
MsCl,CH2Cl2,
-30 to 4 oC
(98%)
![Page 33: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/33.jpg)
Pinacol Rearrangements for Ring Contraction
Y. Kita and co-workers, J. Am. Chem. Soc. 2001, 123, 3214.
N
CpO2COMeOMe
O
BF3•Et2OCH2Cl2, 0 oC
N
CpO2COMeOMe
OBF3
(94%) N
OMeOMe
O
CpO2C
Cp = (1S)-(_)-camphanic acid
O
O
O
R
O
BF3
RCOO
H
O
RCOO1
23
1
2
3HN
HOO
O
O
HO
OH
O
O OMe
fredericamycin A
![Page 34: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/34.jpg)
Pinacol Rearrangements for Ring Expansion
H. Nemoto and co-workers, J. Chem. Soc. Perkin Trans. 1 2000, 16, 2629.
MeOH
OH Pd(OAc)2,HMPA/
THF (1:4)
MeOH
O HX2Pd
MeOH
OX2Pd
MeOH
O
MeOH
O
+
(60%)(2.7:1 A:B)
HOH
O
equilenin A B
![Page 35: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/35.jpg)
Semi-Pinacol Rearrangements for Ring Expansion
F. D. Toste and co-workers, Org. Lett. 2008, 10, 4315.
HO AuPPh3Cl (3 mol %),AgSbF6 (3 mol %),
CH2Cl2, 25 oC
H
H
OMePdCl2(CH3CN)2
DDQ, THF(70%)
H
H
O
H
H (±)-ventricosene
OHH
Au
OHH
Au
(87%)
H
H
O
OHH
AuH
![Page 36: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/36.jpg)
Grob Fragmentations
C. A. Grob, P. W. Schiess, Angew. Chem. Int. Ed. Engl. 1967, 6, 1.
a b c d x
electrofuge nucleofuge
a b c d x+ +
OH
OH
OTsH
HTsO
NaHO
OTsH
O
O
![Page 37: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/37.jpg)
Grob Fragmentations
C. A. Grob, P. W. Schiess, Angew. Chem. Int. Ed. Engl. 1967, 6, 1.
a b c d x
electrofuge nucleofuge
a b c d x+ +
OH
OH
OTsH
HTsO
NaHO
OTsH
O
O
![Page 38: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/38.jpg)
Grob Fragmentations for Ring Expansion
E. J. Corey and co-workers, J. Am. Chem. Soc. 1964, 86, 485
MeMe
MeOTs
HO
MeMe
O
MeNaH
[Grobfrag-
mentation]
MeMe MeH H H
H H H
caryophyllene
![Page 39: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/39.jpg)
Grob Fragmentations
L. A. Paquette and co-workers, J. Am. Chem. Soc. 2002, 124, 6542.
OH
MeBnO
Me
Me
HO
H
MeMe
1. MsCl
2. KOt-Bu
Me
Me
BnO
O
MeMeMe
H(98%)
Me
Me O
MeMeMe
H
O
Ojatrophatrione
![Page 40: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/40.jpg)
Grob Fragmentations
J. D. Winkler and co-workers, Org. Lett. 2003, 5, 1805.
H
H OH
O O
O
O
HO
H
H O
O O
OK2CO3
DMF,75 oC
H
H
OO
OH
OH
H
H
OO
OMe
OH MeI,Ag2O
(68%)
(76%)
core of eleutherobin
![Page 41: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/41.jpg)
Benzylic Acid Rearrangements in Total Synthesis
K. Gademann and co-workers, Chem. Eur. J. 2010, 16, 7692.
R
OH OO
R
O
OO
OO
O
R R
Otaiwaniaquinoid framework
LiHMDSTHF,
-15 oC
R = OMe6%
R = H65%
![Page 42: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/42.jpg)
Benzylic Acid Rearrangements in Total Synthesis
K. Gademann and co-workers, Chem. Eur. J. 2010, 16, 7692.
R
OH OO
R
O
OO
OO
O
R R
Otaiwaniaquinoid framework
LiHMDSTHF,
-15 oC
R = OMe6%
R = H65%
![Page 43: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/43.jpg)
Favorskii Rearrangements in Synthesis
H. O. House and co-workers, J. Org. Chem. 1965, 30, 2948.
Cl
H
O
H
O
H
O OMe
H
O OMe
NaOMe
MeOH
![Page 44: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/44.jpg)
Favorskii Rearrangements in Synthesis
H. Takeshita and co-workers, J. Org. Chem. 1994, 59, 6490.
ClO O
OH
KOH;acid
(88%)
![Page 45: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/45.jpg)
"Quasi-Favorskii" Rearrangement for Ring Contraction
M. Harmata and S. Wcharasindhu, Org. Lett. 2005, 7, 2563.
O
BrMeMe
LiOBr +
THF,-78 oC
Me
Me-30 oC
(90%) O
MeMe
(from [4+3]reaction)
O
H
AcO
H
O
Me Me
O
H
AcOCO2Me
OAc
tricycloclavulone
![Page 46: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/46.jpg)
Ring Contraction of Cross-Conjugated Dienones
K. C. Nicolaou and co-workers, Angew. Chem. Int. Ed. 2001, 40, 3679.
OO
Osantonin
isophotosantoniclactone
OO
OO
O
O
OO
O
H2O
O
O
O
HOH
Dozensof
natural products
(33%)
hν
AcOH/H2O
![Page 47: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/47.jpg)
Ring Contraction of Cross-Conjugated Dienones
K. C. Nicolaou and co-workers, Angew. Chem. Int. Ed. 2001, 40, 3679.
OO
Osantonin
isophotosantoniclactone
OO
OO
O
O
OO
O
H2O
O
O
O
HOH
Dozensof
natural products
(33%)
hν
AcOH/H2O
![Page 48: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/48.jpg)
Norrish Type-1 Cleavage Pathways
K. C. Nicolaou and co-workers, Angew. Chem. Int. Ed. 2001, 40, 3679.
Me
MeO OO
H
Me
MeO O
H
Me
MeO OO
H
Me
MeO O
H
hν
(90%)
![Page 49: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/49.jpg)
Wolff Rearrangements
L. Wolff, Liebigs Ann. Chem. 1902, 325, 129.
ON2
ON N Ag2O,
H2O
O
OH
[or hv, H2O]
ON N O
O• O
O
[1,2]
Ag2O or hνH2O
![Page 50: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/50.jpg)
Wolff Rearrangements
L. Wolff, Liebigs Ann. Chem. 1902, 325, 129.
ON2
ON N Ag2O,
H2O
O
OH
[or hv, H2O]
ON N O
O• O
O
[1,2]
Ag2O or hνH2O
![Page 51: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/51.jpg)
The Wolff Photochemical Rearrangement
V. Mascitti, E. J. Corey, J. Am. Chem. Soc. 2004, 126, 15664.For a review, see: W. Kirmse, Eur. J. Org. Chem. 2002, 2193.
O
N2•O
O
CO2MeCO2H
pentacycloanemmoxic acid
hν
MeOH
MeOH, 2 h
(72%)
![Page 52: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/52.jpg)
O O
Wolff Rearrangements
P. A. Grieco and co-workers, J. Am. Chem. Soc. 1999, 122, 9891.L. N. Mander and co-workers, J. Am. Chem. Soc. 1997, 120, 3828.
O
O
OMe
MeOMOM
BnO
H H
H O OMe
MeOMOM
BnO
H H
H
MeO2C
1. NaH, HCO2Et2. TsN3
3. hν, MeOH(48%)
HO
ON2
BnO2C H
hν, MeOH O O
HO
BnO2C H CO2Me(79%)
![Page 53: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/53.jpg)
O O
Wolff Rearrangements
P. A. Grieco and co-workers, J. Am. Chem. Soc. 1999, 122, 9891.L. N. Mander and co-workers, J. Am. Chem. Soc. 1997, 120, 3828.
O
O
OMe
MeOMOM
BnO
H H
H O OMe
MeOMOM
BnO
H H
H
MeO2C
1. NaH, HCO2Et2. TsN3
3. hν, MeOH(48%)
HO
ON2
BnO2C H
hν, MeOH O O
HO
BnO2C H CO2Me(79%)
![Page 54: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/54.jpg)
Wolff Rearrangement Strategy to Access Dolabellatrienone
Me
Me
Me
H O
Me
Me
Me
H
CO2Me
Me
Me
Me
H
Me
Me
Me
H
O
Me
Me
Me
H O
N2
Me
Me
Me
H
O
MeMe
OHCO2Me
dolabellatrienone
[Wolffrearrangement]
![Page 55: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/55.jpg)
Wolff Rearrangement Strategy to Access Dolabellatrienone
Me
Me
Me
H O
Me
Me
Me
H
CO2Me
Me
Me
Me
H
Me
Me
Me
H
O
LDA, -78 °C, THF;O2, P(OEt)3
2. NaIO4 on silica gel
1. NaHMDS, -78 °C, THF; HCO2Et, -78→0 °C
(82% overall)
Me
Me
Me
H O
N2
hν, 450 W,MeOH,
25 °C, 2 h2. TsN3, Et3N CH2Cl2
(80%)
Me
Me
Me
H
O
MeMe (86% overall)
1. LiAlH4
(73%)
OHCO2Me
dolabellatrienone
[Wolffrearrangement]
![Page 56: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/56.jpg)
New Wolff Rearrangement Strategy to Access Dolabellanes
Me
Me
Me
H O
Me
Me
Me
H
Me
Me
Me
H O ON2
![Page 57: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/57.jpg)
New Wolff Rearrangement Strategy to Access Dolabellanes
Me
Me
Me
H O
Me
Me
Me
H
Me
Me
Me
H
Me
Me
Me
H
Me
Me
Me
H O
[Wolffrearrange-
ment]
ON2
CO2MeCO2Me
severalnatural
products
![Page 58: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/58.jpg)
Wolff Rearrangement Strategy to Access Dolabellatrienone
Me
Me
Me
H O
Me
Me
Me
H
Me
Me
Me
H O(79%)
ON2
LiHMDS,-78 °C, THF;
TMSCl;IBX•MPO,
DMSO, 25 °C(79%)
Trisyl azide,BnEt3NCl,
18-Crown-6.benzene/
66% aq.KOH,45 °C, 48 h
N
OMe
OMPO
OI
O
OHO
IBX
K. C. Nicolaou, T. Montagnon, P. S. Baran, Angew. Chem. Int. Ed. 2002, 41, 993.L. Lombardo, L. N. Mander, Synthesis 1980, 368.
![Page 59: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/59.jpg)
Wolff Rearrangement Strategy to Access Dolabellatrienone
Me
Me
Me
H O
Me
Me
Me
H
Me
Me
Me
H
Me
Me
Me
H O
hν, 450 W,MeOH,
25 °C, 2 h
(79%)[Wolff
rearrange-ment]
ON2
CO2Me
LiHMDS,-78 °C, THF;
TMSCl;IBX•MPO,
DMSO, 25 °C(79%)
Trisyl azide,BnEt3NCl,
18-Crown-6.benzene/
66% aq.KOH,45 °C, 48 h
N
OMe
OMPO
OI
O
OHO
IBX
K. C. Nicolaou, T. Montagnon, P. S. Baran, Angew. Chem. Int. Ed. 2002, 41, 993.L. Lombardo, L. N. Mander, Synthesis 1980, 368.
![Page 60: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/60.jpg)
Wolff Rearrangement Strategy to Access Dolabellatrienone
Me
Me
Me
H O
Me
Me
Me
H
Me
Me
Me
H
Me
Me
Me
H
Me
Me
Me
H O
hν, 450 W,MeOH,
25 °C, 2 h
(79%)[Wolff
rearrange-ment]
ON2
CO2MeCO2Me
LiHMDS,-78 °C, THF;
TMSCl;IBX•MPO,
DMSO, 25 °C(79%)
Trisyl azide,BnEt3NCl,
18-Crown-6.benzene/
66% aq.KOH,45 °C, 48 h
N
OMe
OMPO
OI
O
OHO
IBX
DBU,115 °C, 18 h
(68%)
K. C. Nicolaou, T. Montagnon, P. S. Baran, Angew. Chem. Int. Ed. 2002, 41, 993.L. Lombardo, L. N. Mander, Synthesis 1980, 368.
![Page 61: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/61.jpg)
Wolff Rearrangement Strategy to Access Dolabellanes
Me
Me
Me
H
Me
Me
Me
H
Me
Me
Me
H(67%)
CO2Me
E. J. Corey, R. S. Kania, Tetrahedron Lett. 1998, 39, 741.J. S. Kingsbury, E. J. Corey, J. Am. Chem. Soc. 2005, 127, 13813.
MeMe
OHpalominol
O
Me Me
dolabellatrienone
MeLi,THF, -20°C
PDC,4 A M.S.
CH2Cl2, 25°C(92%)
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Wolff Rearrangement Strategy to Access Dolabellanes
Me
Me
Me
H
Me
Me
Me
H
Me
Me
Me
H(67%)
CO2Me
E. J. Corey, R. S. Kania, Tetrahedron Lett. 1998, 39, 741.J. S. Kingsbury, E. J. Corey, J. Am. Chem. Soc. 2005, 127, 13813.
MeMe
OHpalominol
O
Me Me
dolabellatrienone
Me
Me
Me
H O
1. L-Selectride2. LDA, O23. LiAlH4, NaIO4
(51%overall)
MeLi,THF, -20°C
PDC,4 A M.S.
CH2Cl2, 25°C(92%)
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Wolff Rearrangement Strategy to Access Dolabellanes
Me
Me
Me
H
Me
Me
Me
H
Me
Me
Me
H(67%)
CO2Me
E. J. Corey, R. S. Kania, Tetrahedron Lett. 1998, 39, 741.J. S. Kingsbury, E. J. Corey, J. Am. Chem. Soc. 2005, 127, 13813.
MeMe
OHpalominol
O
Me Me
dolabellatrienone
Me
Me
Me
H
Me
Me
Me
HMe MeO
1. L-Selectride2. LDA, O23. LiAlH4, NaIO4
(51%overall)
1. MOMI, i-Pr2NEt, THF, Δ, 12 h2. Li/NH3
Me
Li
β-araneoseneisoedunol
Me
Me
Me
HMe
OH
MeLi,THF, -20°C
PDC,4 A M.S.
CH2Cl2, 25°C(92%)
Et2O, -78°C(82%) (92% overall)
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Planned Synthetic Approach to Presilperfolan-8-ol
with P. Hu, J. Am. Chem. Soc. 2017, 139, 5007.
O
MeMe
Me
Me
H LDA,Br
(90%)(5:1 dr)
[6 gram scale]
O
MeMe
Me
Me
H KHMDS; Comins'reagent(86%)(5:1 rr)
[7 gram scale]
MeMeMe
H
Me
OTf
H
Me
MeMe
MeH
Me O
MeMe
MeOH
presilphiperfolan-8-ol
[RingContraction]Me
Me
MeH
Me
HOH
Pd(OAc)2 (10 mol %),DPEPhos (20 mol %),
Et3N (2 equiv), toluene, 0.1 M, 110 °C
[2 gramscale]
3 steps
[gram scale]
(28% over4 steps)
13 step total synthesis of moleculeFirst 10 steps performed on gram scale
[1 step from(R)-pulegone]
H
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Use of the Wolff Rearrangement to Afford a trans-Fused [3.3.0]-Bicyclooctane
with P. Hu, J. Am. Chem. Soc. 2017, 139, 5007.
MeMe
MeH
Me O
HOH p-ABSA,DBU Me
Me
MeH
Me O
HOR N2
presilphiperfolan-8-ol
MeMe
MeH
Me
HOR
CO2Me*MeMe
MeH
Me
HOR
CHOMeMe
MeH
Me
HOH
(95% over2 steps)
MeMe
MeH
Me O
HORTMSOTf,Et3N
R = TMS
>800 mg prepared
[Wolffrearrange-ment]
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Use of the Wolff Rearrangement to Afford a trans-Fused [3.3.0]-Bicyclooctane
with P. Hu, J. Am. Chem. Soc. 2017, 139, 5007.
MeMe
MeH
Me O
HOH p-ABSA,DBU Me
Me
MeH
Me O
HOR N2
presilphiperfolan-8-ol
MeMe
MeH
Me
HOR
CO2Me*MeMe
MeH
Me
HOR
CHOMeMe
MeH
Me
HOH
(95% over2 steps)
(83%)
MeMe
MeH
Me O
HORTMSOTf,Et3N
R = TMS125 W Hg UV-lamp,
MeOH
>800 mg prepared
[Wolffrearrange-ment]
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Use of the Wolff Rearrangement to Afford a trans-Fused [3.3.0]-Bicyclooctane
with P. Hu, J. Am. Chem. Soc. 2017, 139, 5007.
MeMe
MeH
Me O
HOH p-ABSA,DBU Me
Me
MeH
Me O
HOR N2
presilphiperfolan-8-ol
DIBAL-H;t-BuOH,
Dess-Martinperiodinane Me
Me
MeH
Me
HOR
CO2Me*MeMe
MeH
Me
HOR
CHOMeMe
MeH
Me
HOH
(95% over2 steps)
(83%)
(93%)
MeMe
MeH
Me O
HORTMSOTf,Et3N
R = TMS125 W Hg UV-lamp,
MeOH
>800 mg prepared
[Wolffrearrange-ment]
![Page 68: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/68.jpg)
Use of the Wolff Rearrangement to Afford a trans-Fused [3.3.0]-Bicyclooctane
with P. Hu, J. Am. Chem. Soc. 2017, 139, 5007.
MeMe
MeH
Me O
HOH p-ABSA,DBU Me
Me
MeH
Me O
HOR N2
presilphiperfolan-8-ol
DIBAL-H;t-BuOH,
Dess-Martinperiodinane
1. Rh(PPh3)3Cl2. TBAF Me
Me
MeH
Me
HOR
CO2Me*MeMe
MeH
Me
HOR
CHOMeMe
MeH
Me
HOH
(95% over2 steps)
(83%)
(93%)(40% over2 steps)
MeMe
MeH
Me O
HORTMSOTf,Et3N
R = TMS125 W Hg UV-lamp,
MeOH
>800 mg prepared
[Wolffrearrange-ment]
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Ring Contractions/Expansions: Take-Home Challenge
H.-G. Schmalz and co-workers, Org. Lett. 2012, 14, 3692.
?????
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The Laurencia Family of Haloethers:An Open Biogenetic Question for their Formation
OBr
Me OAc
HOBr
Me
HOO
H
laurefucinlaurencin
O
Br
H
O
H
HBr
laurallene
H
Me
Fujiwara, K. “Total Synthesis of Medium-Ring Ethers from Laurencia Red Algae” in Topics in Heterocyclic Chemistry (Vol. 5), Kiyota, H. (Ed.), Springer-Verlag: Berlin, 2006, pp. 97-148.
laureoxanyne
OBr
MeH
BrO
First member isolated in 1965 by IrieOver 150 members total
Largest subset (>50 members) have 8-membered bromoetherTotal and Formal Syntheses of Laurencin: Murai, Overman, Palenzuela, Holmes,
Hoffmann, Crimmins, Yamamoto, Kim, Fujiwara, Pansare, OrtegaOther Syntheses: Overman, Crimmins, Fujiwara, Boeckman, Hoshi, Kim, Takeda
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The Laurencia Family of Haloethers:An Open Biogenetic Question for their Formation
OBr
Me OAc
H
laurencin
Fujiwara, K. “Total Synthesis of Medium-Ring Ethers from Laurencia Red Algae” in Topics in Heterocyclic Chemistry (Vol. 5), Kiyota, H. (Ed.), Springer-Verlag: Berlin, 2006, pp. 97-148.
O
HO
HO OPivO
O OPiv
O
(92%)
Pb(OAc)4
Murai and co-workers, Tetrahedron Lett. 1992, 33, 4345.
Overman and co-workers, J. Am. Chem. Soc. 1995, 117, 5958.
Crimmins and co-workers, J. Am. Chem. Soc. 1999, 121, 5653.
33 linearsteps total
OAcO
Me
OMe
OPiv
PhS
OAcO
Me OPiv
SPh
OBr
Me OAc
H
laurencin
23 linearsteps total
BF3•OEt2,t-BuOMe
(57%)
OAcO
AcO OTBDPSOBr
Me OAc
H
laurencin
OAcO
AcO OTBDPS(97%)
24 linearsteps totalGrubbs 1
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The Laurencia Family of Haloethers:An Open Biogenetic Question for their Formation
Murai, A. “Biosynthesis of Cyclic Bromoethers from Red Algae” in Comprehensive NaturalProducts Chemistry (Vol. 1), Sankawa, U. (Ed), Elsevier: New York, 1999, pp. 303-324.
OBr
Me OH
HHO
MeOH
crudebromo-
peroxidase
0.015%(0.085%brsm)
laurediol deacetyllaurencin
Murai and co-workers, Chem. Lett. 1994, 2307
HOMe
OHlaurediol
O
Me
Br
HO
H O
Me
Br
HO
HBr
"Br " * 8-memberedbromoether
naturalproducts
"Br "
Our alternative hypothesis:
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The Laurencia Family of Haloethers:An Open Biogenetic Question for their Formation
Murai, A. “Biosynthesis of Cyclic Bromoethers from Red Algae” in Comprehensive NaturalProducts Chemistry (Vol. 1), Sankawa, U. (Ed), Elsevier: New York, 1999, pp. 303-324.
OBr
Me OH
HHO
MeOH
crudebromo-
peroxidase
0.015%(0.085%brsm)
laurediol deacetyllaurencin
Murai and co-workers, Chem. Lett. 1994, 2307
HOMe
OHlaurediol
O
Me
Br
HO
H O
Me
Br
HO
HBr
"Br " * 8-memberedbromoether
naturalproducts
"Br "
Our alternative hypothesis:
![Page 74: Ring Expansion/Contraction Reactions Contractions.pdf6π-Electrocyclic Reactions: One of Three Pericyclic Reactions in a Colchicine Total Synthesis O O O Me Me OPMB XX OTBS A. Eschenmoser](https://reader033.fdocuments.in/reader033/viewer/2022052320/5f0b5aa07e708231d43019f5/html5/thumbnails/74.jpg)
Value and Challenges of a Bis-Oxonium Biosynthetic Intermediate
with D. S. Treitler, A. P. Brucks, W. Sattler, J. Am. Chem. Soc. 2011, 133, 15898.
OBr
Me
HOO
H
laurefucin
OBr
MeH
deacyllaurencinOH
HOMe OH
laurediolMe OH
O H
Br
OH
O H
Br
Me
Br
"Br " "Br "
[loss of Br ]
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Value and Challenges of a Bis-Oxonium Biosynthetic Intermediate
with D. S. Treitler, A. P. Brucks, W. Sattler, J. Am. Chem. Soc. 2011, 133, 15898.
OBr
Me
HOO
H
laurefucin
OBr
MeH
deacyllaurencinOH
HOMe OH
laurediolMe OH
O H
Br
OH
O H
Br
Me
Br
"Br " "Br "
[loss of Br ]
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Value and Challenges of a Bis-Oxonium Biosynthetic Intermediate
with D. S. Treitler, A. P. Brucks, W. Sattler, J. Am. Chem. Soc. 2011, 133, 15898.
OBr
Me
HOO
H
laurefucin
OBr
MeH
deacyllaurencinOH
OBr
Me
O
H
Br
laureioxanyne
HOMe OH
laurediolMe OH
O H
Br
OH
O H
Br
Me
Br
"Br " "Br "
[loss of Br ]
[intramolecularcyclization]
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Value and Challenges of a Bis-Oxonium Biosynthetic Intermediate
with D. S. Treitler, A. P. Brucks, W. Sattler, J. Am. Chem. Soc. 2011, 133, 15898.
OBr
Me
HOO
H
laurefucin
OBr
MeH
deacyllaurencinOH
OBr
Me
O
H
Br
laureioxanyne
HOMe OH
laurediolMe OH
O H
Br
OH
O H
Br
Me
Br
"Br " "Br "
[loss of Br ]
[intramolecularcyclization]
[external nucleophileand SN2]
H2O