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Mn
(III)
Pro
mo
ted
Rad
ical
Rea
ctio
ns
An
Eva
ns g
roup
afte
rnoo
n se
min
ar
by V
icto
r C
ee
Apr
il 27
, 199
9
I. M
n(O
Ac)
3 In
term
olec
ular
Add
ition
sII.
Mec
hani
smIII
. H
exen
yl R
adic
al C
ycliz
atio
nsIV
. H
epte
nyl R
adic
al C
ycliz
atio
nsV
. M
n(pi
c)3
Lead
ing
Ref
eren
ces:
Mel
ikya
n, G
. G. A
ldric
him
ica
Act
a 19
98, 3
1, 5
0
Sni
der,
B. B
. Che
m. R
ev. 1
996,
96,
339
Mel
ikya
n, G
. G. S
ynth
esis
, 199
3, 8
33.
Mel
ikya
n, G
. G. I
n O
rgan
ic R
eact
ions
; Paq
uette
, L. A
. Ed;
Jo
hn W
iley:
New
Yor
k, N
Y, 1
997;
Vol
. 49,
427
.
Iqba
l, J.
Bha
tia, B
. Nay
yar,
N. K
. Che
m. R
ev. 1
994,
94,
519
.
01-t
itle
4/27
/99
1:17
AM
Man
gan
ese
(III)
: A
On
e E
lect
ron
Oxi
dan
t
Mn(
III)
d4
t 2g
e g
e-
Mn(
II) d
5
t 2g
e g
Ele
ctro
nic
Str
uctu
re (
Oh,
hig
h sp
in)
One
Ele
ctro
n O
xida
nts
Co3+
+1e
- →
Co2+
Ce4+
+1e
- → C
e3+
Mn3+
+1e
- →
Mn2+
Fe3+
+1e
- →
Fe2+
Cu2+
+1e
- →
Cu1+
1.92
1.61
1.51
0.77
0.16
E˚
(V)
Rea
ctio
n
Mn+
+-M
n-1+
RH
RH
R-H
+E
lect
ron
Tra
nsfe
r
Sub
stitu
tion
Mn+
+R
HR
Mn+
-Mn-
1+-H
+R
02-M
nint
ro4/
26/9
912
:02
PM
Met
al-I
nd
uce
d C
arb
oxy
met
hyl
Rad
ical
s
O
MeO
O
OM
e2
equi
v C
uBr 2
TH
F, -
78 ˚
C
2 eq
uiv
LDA
99%
MeO
2CC
O2M
e
cis:
tran
s 1:
1
Chu
ng J
. Org
. Che
m. 1
983,
48,
112
5
TM
SO
MeO
OT
MS
OM
e
Me
Me
CH
2Cl 2
, 20 ˚C
2 eq
uiv
TiC
l 4
69%
MeO
2CC
O2M
e
Me
Me
cis:
tran
s 1:
99
Cha
n T
etra
hedr
on 1
983,
39,
847
Ph
O
Me
Me
OT
ES OE
tM
e
Me
OT
ES OE
tP
h
OO
OE
t
cat.
SnC
l 4
IP =
7.7
4 eV
IP =
7.2
5 eV
J. O
rg. C
hem
. 199
6, 6
1, 2
951
J. A
m. C
hem
. Soc
. 199
2, 1
14, 1
0271
Fuk
uzum
i
CH
2Cl 2
, -78
˚C
85%
only
pro
duct
obs
erve
d
++
mix
ture
of i
som
ers
RO
OR
-e-
RO
OR
+
03-m
etal
indu
ced
radi
cals
4/26
/99
3:03
PM
Mn
(III)
Ind
uce
d C
arb
oxy
met
hyl
Rad
ical
s
Me
Mn(
OA
c)3·
2 H
2OO
O
75 %
Bus
h an
d F
inkb
eine
r J.
Am
. Che
m. S
oc. 1
968,
90,
590
3
Me
Mn(
OA
c)3·
2 H
2O
79 %
O
O
Ph
Me
Me
Ph
Hei
ba J
. Am
. Che
m. S
oc. 1
968,
90,
590
5
Hei
ba J
. Org
. Che
m.
1974
, 34,
345
6
O
Me
O
OE
t
Mn(
OA
c)3·
2 H
2O
AcO
H, 4
5 ˚C
+
OM
e
CO
2Et
Ph
57%
IP ~
8.8
eV
AcO
H, ∆
KO
Ac,
AcO
H, ∆
OH
O
OH
O
+ +
IP =
10.
65 e
V
HO
O-e
-
HO
O
04-M
n in
duce
d ra
dica
ls4/
26/9
93:
13 P
M
Mn
(OA
c)3•
2H2O
an
d A
nh
ydro
us
"Mn
(OA
c)3"
Hes
sel C
. Rec
. Tra
v. C
him
. 196
9, 8
8, 5
45.
Sol
id-S
tate
Str
uctu
re o
f Anh
ydro
us M
n(O
Ac)
3 [
Mn 3
O(O
Ac)
6·A
cOH
·OA
c]n
Sol
utio
n S
truc
ture
(A
cOH
)
Mn 2
Mn 1
Mn 3
O O
O
OA
cA
cOM
nM
nH
OA
cH
OA
c
O H
O
OH
n
Mn
Mn
Mn
O OO
H
+A
cO-
O16
Mn 2
Mn 1
Mn 3
Bo
nd
Dis
tan
ce (
Å)
Mn 1
-O16
Mn 3
-O16
Mn 2
-O16
1.84
81.
858
2.10
8C
H3
OO
=
+A
cO-
Mn(
OA
c)3·
nAcO
H
.A trim
eric
sol
utio
n st
ruct
ure
has
been
pro
pose
d
.Dimer
ic a
nd m
onom
eric
spe
cies
may
als
o be
pre
sent
Anh
ydro
usM
n(O
Ac)
3an
dth
edi
hydr
ate
are
indi
stin
guis
habl
ein
solu
tion,
and
unde
rgo
met
athe
sis
with
oth
er a
cids
rea
dily
. T
he c
omm
erci
ally
ava
ilabl
e di
hydr
ate
is th
e m
ost p
opul
ar.
05-M
n(O
Ac)
3 xt
al4/
26/9
93:
17 P
M
Imp
ort
ance
of
Bri
dg
ed M
n C
ente
rs:
Cat
alas
es
Mn
CH
3
OO
=
OH
2
LM
n OH
2
LL
LII
II
Mn O
LM
n OH
2
LL
LII
II
OH
Mn
LM
nL
LL
IIII
O OH+
Mn
LM
nL
LL
IIIIII
O
Mn O
LM
n OH
LL
L
OH
IIIIII
H2O
2
H3O
+
H2O
H+
H2O
H+, H
2O2
H2O
O2
T. t
herm
ophi
lus
Cat
alas
e
H2O
2 +
2 H
3O+ +
2e- →
4 H
2OM
n3+ +
1e-
→ M
n2+
O2
+ 2
H3O
+ +
2e- →
H2O
2 +
2 H
2O
1.78
1.51
0.68
E˚
(V)
Rea
ctio
nC
atal
yzes
the
disp
ropo
rtio
natio
n of
H2O
2:
2 H
2O2 →
O2
+ 2
H2O
Clo
se p
roxi
mity
of t
wo
man
gane
se c
ente
rs
is e
stab
lishe
d by
brid
ging
ace
tate
s
Net
Res
ult:
Red
ox c
hem
istr
y at
the
diffu
sion
-con
trol
led
rate
Pro
pose
d M
echa
nism
Sta
ndar
d R
educ
tion
Pot
entia
ls
Dis
muk
es, G
. C. C
hem
. Rev
. 199
6, 9
6, 2
909.
06-B
ioch
em4/
26/9
93:
33 P
M
Un
iqu
e F
eatu
res
of
Mn
(III)
Att
rib
ute
d t
o t
he
Tri
mer
ic N
atu
re o
f M
n(O
Ac)
3
OC
H3
O
MO
O
MM
= A
g(II)
, Pb(
IV),
Ce(
IV),
Mn(
pic)
3
M =
Mn(
OA
c)3
+C
H3
CO
2
Dec
arbo
xyla
tion
is n
ot a
dom
inan
t pat
hway
Dim
eriz
atio
n is
not
a d
omin
ant p
athw
ay
Abi
lity
to o
xidi
ze fr
ee a
cids
OS
iR3
RO
Cu(
II)R
O
OT
i(IV
), S
n(IV
),M
n(O
Ac)
3
HO
CH
3
O
RO
O
HO
O
O
OH
Mn O
Mn
O
O
Mn
CH
3III
IIIIII
pic
= p
yrid
inec
arbo
xyla
te
Mn(
OA
c)3
Ti(I
V),
Cu(
II)R
O
O
O
OR
07-U
niqu
enes
s M
n4/
26/9
910
:11
PM
Mec
han
ism
of
Mn
(III)
Oxi
dat
ive
Lac
ton
izat
ion
: E
no
lizat
ion
Mn O
Mn
O
O
Mn
CH
3M
n OM
nO
O
Mn
III
IIIIII
III
IIIIII
Eno
l Con
tent
- S
mal
l
[Mn(
OH
2)6]
+3
[Fe(
OH
2)6]
+3
pKa
= 0
.1pK
a =
2.2
Li In
org.
Che
m. 1
996,
35,
469
4
OH
O
OH
OH
K =
4x1
0-20
Gut
hrie
, Can
. J. C
hem
. 199
5, 7
3, 1
395
Act
ivat
ion
by M
n
Fris
tad
J. O
rg. C
hem
. 198
5, 5
0, 1
0
RC
O2H
Mn(
III) R
'O
O
R'
Rp
Ka αααα
-H (
este
r)re
lati
ve r
ate
H Cl
SO
2Ph
CO
2Me
CN
25 22 14 13 9
11.
1 x
101
3.8
x 10
3
1.1
x 10
4
4.0
x 10
5
R
Eno
lizat
ion
Pro
pose
d as
the
Rat
e-D
eter
min
ing
Ste
p
Ioni
zatio
n P
oten
tials
: C
arbo
nyl v
s. E
nol E
ther
HC
H3
O
H
OM
e
IP =
10.
2 eV
IP =
9.0
eV
AcO
K
08-M
echa
nism
Mn_
24/
26/9
910
:19
PM
Mec
han
ism
of
Mn
(III)
Oxi
dat
ive
Lac
ton
izat
ion
: E
no
lizat
ion
Mn O
Mn
O
O
Mn
CH
3M
n OM
nO
O
Mn
III
IIIIII
III
IIIIII
Fris
tad
Tet
rahe
dron
198
6, 4
2, 3
429
Ole
finLa
cton
eS
olve
nt E
noliz
atio
n
time
(min
)
mmolCom
paris
on o
f Eno
lizat
ion
and
Rea
ctio
n R
ates
Rat
e of
eno
lizat
ion
~ r
ate
of d
eute
rium
inco
rpor
atio
n:
Mn(
III)
KO
Ac,
ref
lux
CH
3CO
2H +
CD
3CO
2DC
HnD
3-nC
O2H
(D)
The
rea
ctio
n:
C8H
17O
OC
8H17
Mn(
III),
KO
Ac
HO
Ac,
ref
lux
Pre
senc
e of
Mn(
III)
has
no e
ffect
on
D in
corp
orat
ion!
Con
clus
ion:
Onc
e en
oliz
atio
n oc
curs
, rap
id e
lect
ron
tran
sfer
and
rea
ctio
n en
sue.
Eno
lizat
ion
is ir
reve
rsib
le
G. I
. Nis
hiki
n J.
Org
. Che
m. U
SS
R 1
978,
14,
189
4
Alte
rnat
ive
Con
clus
ion:
Eno
lizat
ion
and
elec
tron
tr
ansf
er o
ccur
in a
con
cert
ed s
tep
O
HOA
cM
nIII
OM
nII
OM
nII
1e-
09-M
echa
nism
Mn_
24/
26/9
99:
24 P
M
Mec
han
ism
of
Mn
(III)
Oxi
dat
ive
Lac
ton
izat
ion
: R
adic
al A
dd
itio
nM
n OM
nO
O
Mn
CH
2R
Mn O
Mn
O
O
Mn
R
III
IIIII
III
IIIII
R2
R1
R2
R1
OA
cOA
c
O
O
R2
R1
Mn(
III)
Liga
nd E
lect
ron
Tra
nsfe
rA
lken
e E
lect
ron
Tra
nsfe
r
IP (
eV)
Alk
ene
Alk
ene
Ele
ctro
n T
ran
sfer
(%
)
1-he
xene
9.65
04-
met
hyls
tyre
ne8.
206
inde
ne8.
1454
tran
s-st
ilben
e8.
0096
HO
Ac
+R
3
O
OH
+
R3
= H
R3
R3
= C
O2M
e
0 0 0 0
Fris
tad
Tet
rahe
dron
, 198
6, 4
2, 3
429
10-M
echa
nism
Mn
4/26
/99
10:3
6 P
M
Mec
han
ism
of
Mn
(III)
Oxi
dat
ive
Lac
ton
izat
ion
: O
xid
atio
n a
nd
C
ycliz
atio
n
Mn O
Mn
O
O
Mn
R
III
IIIII
Mn O
Mn
O
O
MnII
IIIII
Fris
tad:
No
evid
ence
fo
r ca
rboc
atio
n
Mn O
Mn
O
O
Mn
R
III
IIIII
Mn O
Mn
O
O
Mn
R
II
IIIII
Mn O
Mn
O
O
MnII
IIIII
R
Hei
ba:
Oxi
datio
n to
a ca
rboc
atio
n
Mn(
OA
c)3
KO
Ac,
HO
Ac,
∆O
O
63%
OA
c
CO
2H
1%
CO
2H+
- OA
c
Mn O
Mn
O
O
Mn
R
III
IIIII
Mn O
Mn
O
O
MnIII
IIIII
R
Mn O
Mn
O
O
MnII
IIIII
R
Fris
tad:
Rad
ical
C
ycliz
atio
n
Hei
ba J
. Am
. Che
m. S
oc. 1
971,
93,
524
Fris
tad
J. O
rg. C
hem
. 198
5, 5
0, 1
0
11-M
echa
nism
Mn
4/27
/99
1:19
AM
Intr
od
uct
ion
of
Co
pp
er (
II)
O
O
2
Cu(
OA
c)2
+
97%
3%A
cOH
Koc
hi J
. Am
. Che
m. S
oc. 1
965,
87,
485
5
CO
2+
O1-
octe
ne, M
n(O
Ac)
3, M
C9H
19
OO
O
C6H
13
OA
c
++
AcO
H, K
OA
c, 8
5 ˚C
M O
xid
ant
Rel
ativ
e k o
x
-C
e(IV
)C
u(II)
1 12 350
Hei
ba J
. Am
. Che
m. S
oc. 1
971,
93,
524
Ko
chi:
Cu
(II)
as
a ra
dic
al
oxi
dan
t
Hei
ba:
Ap
plic
atio
n t
oM
n(I
II) r
eact
ion
sC
5H11
Co
pp
er (
II) O
xid
atio
nM
ech
anis
m
O
RC
u(O
Ac)
2
O
R
Cu(
OA
c)2
III
O
R+
+C
u(O
Ac)
O
R
O
R
Nu
Elim
inat
ion
is u
sual
ly
the
dom
inan
t pat
hway
12-C
u_2
4/26
/99
11:0
1 P
M
Inte
rmo
lecu
lar
Cyc
lizat
ion
s: S
tud
ies
To
war
d
Po
do
ph
yllo
toxi
n
O O
OE
t
OO
MeO
OM
e
OM
e
CO
2Et
2.2
Mn(
OA
c)3
AcO
H, 3
0 m
inO
EtO
2CC
O2E
t
OM
e
OM
e
OM
e
O O56
%
5 eq
uiv
SnC
l 4
81%
O O
O
CO
2Et
CO
2Et
MeO
OM
e
OM
e
O O
OH
MeO
OM
e
OM
eO O
Pod
ophy
lloto
xin
O O
O
CO
2Et
CO
2Et
MeO
OM
e
OM
e
+
Fris
tad
Tet
rahe
dron
Let
t. 19
87, 2
8, 1
493
rt, 7
0 h
13-I
nter
mol
ec.
cycl
izn
4/27
/99
12:0
4 A
M
Intr
amo
lecu
lar
Cyc
lizat
ion
s
OO
OR
X
OO
OR
X
OO
OR
X
OO
OR
RO
OO
XX
Mon
ocyc
lizat
ions
Hig
her
cycl
izat
ions
OO
OR
R
R
14-I
ntra
mol
ec c
ycl i
ntro
4/13
/99
9:26
AM
Hex
enyl
Rad
ical
Cyc
lizat
ion
-
Is E
qu
ilib
rati
on
Po
ssib
le?
k exo
k -ex
ok -
endo
k end
o
k ter
mk t
erm
Kin
etic
s: k
exo/
k end
o de
pend
s on
sub
stitu
tion
patte
rn
Equ
ilibr
atio
n: e
xten
t of r
ing
open
ing
depe
nds
on r
elat
ive
mag
nitu
de o
f kte
rm
CH
3
Rep
rese
ntat
ive
rate
s:k e
xo =
2 x
105 s
-1
k end
o =
4 x
103 s
-1
k ter
m =
3 x
106 M
-1 s
-1 (
Bu 3
SnH
)
15-H
exen
yl C
ycliz
n In
tro
4/27
/99
12:0
7 A
M
Rev
ersi
ble
vs.
Irre
vers
ible
Rad
ical
Cyc
lizat
ion
t-B
uO3C
CN
CO
2Et
∆, C
6H12
CO
2Et
CN
(PhC
O2)
2
CH
3
CN CO
2Et
CN C
O2E
t
1486
CN CO
2Et
The
sam
e ra
tio is
obs
erve
d w
hen
the
follo
win
g ra
dica
l pre
curs
ors
are
used
:
Rat
e of
H a
bstr
actio
n <
rat
e of
rin
g op
enin
g
hν, b
enze
neC
O2M
eC
O2M
e
(Me 3
Sn)
2C
O2M
e
CO
2Me
CO
2Me
CO
2Me
9010
I
+ +
Rat
e of
iodi
ne a
bstr
actio
n >
rat
e of
rin
g op
enin
g
I
Cur
ran
J. O
rg. C
hem
. 198
9, 5
4, 3
140
10 m
in
48 h
M. J
ulia
Acc
. Che
m. R
es. 1
971,
4, 3
86
Rat
e of
oxi
datio
n >
rat
e of
rin
g op
enin
g
Cu(
OA
c)2
CO
2Me
CO
2Me
Mn(
OA
c)3
CO
2Me
CO
2Me
55 ˚
C, 4
3 h
Sni
der
J. A
m. C
hem
. Soc
. 19
91, 1
13, 6
609
O
CO
2Me
O+
+
CO
2Me
CO
2Me
937
k ope
n ~
1x1
04 s-1
k I ~
2x1
09 M
-1s-1
k oxi
dn ~
1x1
06 M-1
s-1
t-B
uO3C
I
16-H
exen
yl C
ycliz
n In
tro
24/
27/9
912
:13
AM
Hex
enyl
Rad
ical
Cyc
lizat
ion
O
CO
2Me
OH
CO
2Me
O
CO
2Me
Sni
der
J. O
rg. C
hem
. 198
9, 5
4, 3
8
Pet
erso
nTet
rahe
dron
Let
t. 19
87, 6
109
OO
OR
X
R1
R2
R1
R2
R3
cond
ition
sR
1
RR
3
sub
stra
teco
nd
itio
ns
5-ex
o6-
endo
pro
du
cts
5-ex
o
- -
21%
70%
6-en
do
94%
91%
5% -
R - -
4 M
n(O
Ac)
3C
u(O
Ac)
2
4 M
n(O
Ac)
3C
u(O
Ac)
2
2 M
n(O
Ac)
3C
u(O
Ac)
2
R1
H Me
H H
R2
H Me
H H
R3
H H Me
Ph
2 M
n(O
Ac)
3C
u(O
Ac)
2P
h
OA
c
refe
ren
ce
AcO
H
R2
End
ocyc
lic k
eton
e an
d th
e su
bstit
utio
n pa
ttern
of t
he a
lken
e co
ntro
l the
mod
e of
cyc
lizat
ion
Sim
ilar
sele
ctiv
ity s
een
for α
-sub
stitu
ted β-
keto
este
rs
Sni
der
J. O
rg. C
hem
. 198
5, 5
0, 3
661
Pet
erso
nTet
rahe
dron
Let
t. 19
87, 6
109
O
Me
MeO
CO
Me
5-(e
nole
ndo)
-exo
-trig
disf
avor
ed r
elat
ive
to6-
(eno
lend
o)-e
xo-t
rig S
imila
r se
lect
ivity
see
n fo
r α
-rad
ical
s ge
nera
ted
by a
tom
tran
sfer
17-H
exen
yl M
onoC
ycliz
n 4/
13/9
910
:11
AM
OC
O
Hex
enyl
Rad
ical
Bic
ycliz
atio
n
2 eq
uiv
Mn(
OA
c)3
Cu(
OA
c)2
O
CO
2Me
OC
O2M
e
O
OO
R
48%
86%
77%
18% - -
RR
R=
HR
=C
H3
R=
OP
O(O
Et)
2
J. O
rg. C
hem
. 198
7, 5
2, 5
487
J. O
rg. C
hem
. 199
1, 5
5, 5
544
OH
H
HC
O2H
Me
HO
Gib
bere
lic A
cid
MeO
2CO
PO
(OE
t)2
O
AcO
H
O
CO
2Et
Ph
2 eq
uiv
Mn(
OA
c)3
AcO
H
CO
2Et
HC
H3
O
74%
Sni
der
Tet
rahe
dron
Let
t. 19
87, 2
8, 8
45
Sni
der
OO
OR
X
18-H
exen
ylbi
Cyc
lizn
4/13
/99
10:3
1 A
M
Hex
enyl
Rad
ical
Cyc
lizat
ion
:S
tud
ies
To
war
d t
he
Gin
kgo
lides
OO
OR
X
O
CO
2HA
cOH
, rt,
1h52
%, o
ne is
omer
O
O
OO
H
OO
H OH t-
Bu
H
O
O
O
Mn(
OA
c)3
O
HH H
H
NaH
met
hyl b
rom
oace
tate
O
OO
HH
H
CO
2Me
Al/H
g
TH
F/H
2OO
OO
HHH
H
CO
2Me
1) M
sCl,
TE
A
2) L
iOH
; H+
65%
, tw
o st
eps
79%
O
O
HH
H
O
O
O
O O
H
OO
H OH t-
Bu
O
O
H
OO
H OH t-
Bu
OO
HO
lact
one
annu
latio
n
bilo
balid
e
Mn(
III)
Cor
ey J
. Am
. Che
m. S
oc. 1
984,
106
, 538
418
a-H
exen
yl B
iloba
lide
O4/
13/9
910
:18
AM
H3C
CH
3
CH
3
HC
H3
H3C
CH
3
HH
O
H3C
CH
3
OH
Bre
slow
Tet
rahe
dron
Let
t. 19
62, 1
207
squa
lene
lano
ster
ol
OA
c
(PhC
O2)
2
CuC
l, C
u(O
Bz)
2, ∆
Ace
toni
trile
20 -
30%
OA
c
H3C H
H3C
CH
3
BzO
Bio
syn
thet
ic R
adic
al C
ycliz
atio
n H
ypo
thes
is
Bre
slow
Tet
rahe
dron
Let
t. 19
68, 1
837
How
ever
, in
1966
the
impo
rtan
ce o
f squ
alen
e ox
ide
was
est
ablis
hed:
Cor
ey J
. Am
. Che
m. S
oc. 1
966,
88,
475
0;
van
Tam
elen
, J. A
m. C
hem
. Soc
. 196
6, 8
8, 4
752
Pro
posa
l:
Exp
erim
ent:
18b-
Hex
enyl
pol
yCyc
lizn
bio
4/13
/99
10:3
7 A
M
Hex
enyl
Rad
ical
Bic
ycliz
atio
n:
P
od
oca
rpic
Aci
d
OM
e
Me
CO
2Et
O
AcO
H, r
t, 1h
2 eq
uiv
Mn(
OA
c)3
OM
e
Me
HM
eC
O2E
t
O
OM
e
Me
HM
eC
O2E
t
Zn,
HC
l
50%
, one
isom
er60
%
OM
e
Me
HM
eC
O2H
(±)
Pod
ocar
pic
Aci
d
Sni
der
J. O
rg. C
hem
. 198
5, 5
0, 3
659
Est
er h
ydro
lysi
s: W
elch
J. O
rg. C
hem
. 197
7, 4
2, 2
879
O Me
CO
2Et
OM
e
OO
OR
X
18c-
Hex
enyl
pol
yCyc
lizn
Pod
o4/
27/9
912
:37
AM
Hex
enyl
Rad
ical
Tet
racy
cliz
atio
n:
B
eyer
-15-
ene-
3,19
-dio
l
OO
OR
X
O
CO
2Et
Me
MeO
H, r
t, 3h
Mn(
OA
c)3
Cu(
OA
c)2
35%
, one
isom
er
Me
H
Me
HM
eC
O2E
t
O
O Me
CO
2Et1)
LA
H
2) O
3, D
MS
O
Me
H
Me
HM
e
HO
1) H
2NN
HT
s
52 %
2) e
xces
s n-
BuL
i
33%
HO
Me
H
Me
HM
e
HO
HO
Bey
er-1
5-en
e-3,
19-d
iol
Sni
der
J. O
rg. C
hem
. 199
8, 6
3, 7
945
+ 4
% 6
-8 b
icyc
le
18d-
Hex
enyl
pol
yCyc
lizn
beye
rol
4/13
/99
10:4
2 A
M
Hex
enyl
Rad
ical
Cyc
lizat
ion
:O
-Su
bst
itu
ted
Mal
on
ates
α-u
nsub
stitu
ted
α-s
ubst
itute
d
OO
OR
X
X=
O
O
O
CO
2Me
KO
Ac,
AcO
H, ∆
O
O
CO
2Me
43%
O
O
CO
2Me
KO
Ac,
AcO
H, ∆
73%
Me
2 eq
uiv
Mn(
OA
c)3
2 eq
uiv
Mn(
OA
c)3
Cu(
OA
c)2
Cu(
OA
c)2
OO
OO
Me
H
Ber
tran
d T
etra
hedr
on L
ett.
1989
, 30,
331
O
O
CO
2Me
AcO
H, ∆
54%
Me
Cu(
OA
c)2
O
OC
O2M
eM
eS
nide
r T
etra
hedr
on 1
993,
49,
944
7
O
O
CO
2Me
KO
Ac,
AcO
H, ∆
21%
Cu(
OA
c)2
Me
OO
OO
Me
Me
O
O
CO
2Me
Me
21
2:1
:
2 eq
uiv
Mn(
OA
c)3
2 eq
uiv
Mn(
OA
c)3
19-H
exen
yl M
onoC
ycliz
n O
4/13
/99
10:5
3 A
M
Mn
(III)
Cyc
lizat
ion
s: C
hir
al A
uxi
liari
es
R
O
Me
2 M
n(O
Ac)
3
AcO
HC
u(O
Ac)
2
O
RM
e
NO
OO
Ryi
eld
(%
)se
lect
ivit
y (%
de)
+M
e
RO
12
pro
du
ct
SP
h
O
--
-
144
100
N
OM
e
Me
228
92
Ph O
O
Me
290
86
Et 2
N
O-
45-
Sni
der
J. O
rg. C
hem
. 199
1, 5
6, 3
28; J
. Org
. Che
m. 1
993,
58,
764
019
a-A
sym
met
ric C
ycliz
atio
n4/
13/9
911
:00
AM
Mn
(III)
Cyc
lizat
ion
s: ββββ
-Ket
osu
lfo
xid
e
Sni
der
J. O
rg. C
hem
. 199
1, 5
6, 3
28O
S
Me
O
Ph
SM
e
O
OP
hS
OP
h
O
Me
PhO
S
O
Me
O
PhO
SM
e
O Me
CO
2Et
OM
e
Pro
pose
d cy
cliz
atio
n ge
omet
ry in
pod
ocar
pic
acid
syn
thes
is
sulfo
xide
pse
udo-
axia
lsu
lfoxi
de p
seud
o-eq
uato
rial
O
SO
Ph
19b-
Asy
mm
etric
Cyc
lizat
ion
4/13
/99
11:0
1 A
M
Me
Mn
(III)
Cyc
lizat
ion
s: ββββ
-Ket
oam
ide,
ββββ-K
eto
este
r
O
O
Me
RO
N
O
Ph
OO
Me
The
orig
in o
f dia
ster
eose
lect
ivity
is d
iffic
ult t
o ra
tiona
lize
whe
n th
e ra
dica
l cen
ter
is te
rtia
ry a
nd th
e co
nfor
mat
ion
is c
ontr
olle
d by
A1,
3 st
rain
.
N
HR
O
X
Me
17:1
Me
N
Me
t-B
u
O
Me
H
4:1
A1,
3 st
rain
min
imiz
ed
Gie
se T
etra
hedr
on L
ett.
1993
, 33,
263
7P
orte
r J.
Am
. Che
m. S
oc. 1
991,
113
, 700
2
92%
de
86%
de
19c-
Asy
mm
etric
Cyc
lizat
ion
4/27
/99
12:4
6 A
M
Mn
(III)
Cyc
lizat
ion
s: C
hir
al A
uxi
liari
es
OM
e
Me
CO
2R
OA
cOH
, 15 ˚C
, 1h,
50%
, 75%
de
2 M
n(O
Ac)
3
OM
e
Me
HR
O2C
Me
O
R =
(-)
-phe
nmen
thyl
MeO
H, 0
˚C
, 8h,
56%
, 82%
de
Sni
der
J. O
rg. C
hem
. 199
3, 5
8, 7
640
SO
2N
O O
2 M
n(O
Ac)
3
Cu(
OA
c)2
HO
Ac,
4h,
rt
49%
, 50%
de
Me
H
OX
c
Zor
etic
Tet
rahe
dron
Let
t. 19
92, 3
3, 2
637
SN O
O
O H
O
O
SN O
O
O HS
N O
O
O H
A s
imila
r ex
ampl
e:
27:1
Cur
ran;
Por
ter;
Gei
se In
Ste
reoc
hem
istr
y of
Rad
ical
Rea
ctio
ns,
VC
H:
Wei
nhei
m, 1
996,
198
.19
d-A
sym
met
ric C
ycliz
atio
n4/
13/9
911
:04
AM
CO
2Me
Hep
ten
yl R
adic
al B
icyc
lizat
ion
67%
Sni
der
J. O
rg. C
hem
. 198
7, 5
2, 5
487
2 eq
uiv
Mn(
OA
c)3
Cu(
OA
c)2
CO
2R'
O
R1
OC
O2R
'
R1
68%
Sni
der
Tet
rahe
dron
199
1, 4
7, 8
663
Sni
der
Tet
rahe
dron
Let
t. 19
88, 2
9, 5
209
subs
trat
eco
nditi
ons
6-ex
o7-
endo
prod
ucts
(%
yiel
d)
refe
renc
e
12%
32%
O
CO
2R'
R1
R2
R2
R2
R1=
R2=
H; R
'=E
t
R1=
Me,
R2=
H; R
'=M
e
R1=
H, R
2=M
e; R
'=M
e
-
-
6-ex
o7-
endo
O
Me
CO
2Me
HO
CO
2Me
HM
e H
H
Me
O
CO
2Me
H
Me
O
HH
O
CO
2Me
HH
Me25
˚C
, 13
h
AcO
H
OO
OR
X
25 ˚
C
25 ˚
C
+
20-H
epte
nyl B
iCyc
lizn
4/13
/99
11:1
6 A
M
Me
Hep
ten
yl R
adic
al C
ycliz
atio
n:
D
ihyd
rop
alle
scen
sin
D
OO
OR
X
Me
Me
O
Me
Me
1) L
i, N
H3,
t-B
uOH
2) L
DA
, MeO
2CC
N
Me
Me
O
Me
CO
2Me
52%
2 eq
uiv
Mn(
OA
c)3
Cu(
OA
c)2
AcO
H, r
t, 3h
61%
, one
isom
er
Me
Me
H
H
O
CO
2Me
1) L
iCl,
DM
SO
, ∆
2) (
i-Pr)
2NM
gBr;
T
MS
Cl,
Et 3
N3)
mC
PB
A
64%
, one
isom
er
Me
Me
H
H
O
OH
1)T
MS
Li
2) K
2CO
3, M
eOH
Me
Me
H
HO
HOH
81%
HgS
O4
62%
Me
Me
H
H
2N H
2SO
4
O
2,3-
dihy
drop
alle
scen
sin
D
O
Me
cont
rols
faci
al s
elec
tivity
of "
O"
addi
tion
cont
rols
faci
al
sele
ctiv
ity o
f Nu
addi
tion
2
3
J. D
. Whi
te T
etra
hedr
on L
ett.
1990
, 31,
59
21-H
epte
nyl D
ihyd
ropa
llesc
ensi
n4/
13/9
911
:20
AM
Hep
ten
yl R
adic
al C
ycliz
atio
n:
U
pia
l an
d 1
4-ep
iUp
ial
Me
Me
O
Me
Me
CH
O
7 st
eps
Me
OM
OM
Me
CO
2HM
eO2C
Me
OM
OM
Me
CO
2HM
eO2C
O
OM
OM
H
O
CO
2Me
Me
Me
O
MO
MO
O
CO
2Me
Me
Me
H
Mn(
OA
c)3
HO
Ac,
70 ˚C
68% 9%"
∆
Me
Me
O
OE
t
1) L
DA
, iod
ohex
ene
2) H
Cl,
TH
F/H
2O
Me
O
O
Me
57%
, 6:1
2 eq
uiv
Mn(
OA
c)3
HO
Ac,
25 ˚C
, 2h
Cu(
OA
c)2
Me
Me
O
O
O
Me
Me
O
CH
O
85%
, mix
ture
of f
our
dias
tere
omer
s
Upi
al
Sni
der
Tet
rahe
dron
199
5, 5
1, 1
2983
Paq
uette
Tet
rahe
dron
198
7, 4
3, 5
567
Paq
uette
: 14
-epi
Upi
al
Sni
der:
Upi
al F
orm
al S
ynth
esis
Tas
chne
r J.
Am
. Che
m. S
oc.
1985
, 107
, 557
0
1:1
Upi
al
14
22-H
epte
nyl e
piup
ial
4/27
/99
1:02
AM
Hep
ten
yl R
adic
al C
ycliz
atio
n:
Gym
no
mit
rol
O
Me
Me
1) L
iHM
DS
,
2) N
aH, M
eIO
Me
Me
Me
Me
1-io
do-2
-but
yne
1) 2) L
DA
, TM
SC
l
30%
, 6:1
O
Me
Me
Me
TM
S
65 %
15 M
n(O
Ac)
3
9:1
EtO
H/H
OA
c90
˚C
, 22
h
Me
Me
Me
O
TM
S62
%, ~
1:1
2) N
aBH
4
1) H
OA
c, 1
00 ˚
C
70%
Me
Me
Me
HO
H
(±)
gym
nom
itrol
Pre
cede
nt:
Syn
thes
is:
O
Me
15 e
quiv
Mn(
OA
c)3
9:1
EtO
H/H
OA
c90
˚C
, 20
hR
Me
O
R
+
Me
O
4%41
%R
=H
R=
TM
S
R
58%
0%
H2N
KN
H
Sni
der
J. O
rg. C
hem
. 199
7, 6
2, 1
970
23-H
epte
nyl g
ymno
mitr
ol4/
13/9
911
:25
AM
Man
gan
ese
Tri
s(2-
pyr
idin
ecar
bo
xyla
te)
Mn(
pic)
3NOO
Mn
3
Syn
thes
is:
Ray
Aus
t. J.
Che
m. 1
966,
19,
173
7
F
orm
erly
a w
ater
-red
ox m
odel
for
phot
osys
tem
II.
Intr
oduc
tion
in s
ynth
etic
che
mis
try:
Nar
asak
a C
hem
Let
t. 19
89, 2
169
O
Ph
O
OH
Me
+P
h
OT
BS
2.5
Mn(
pic)
3
DM
F, r
t, 2h
O
Ph
Me
O
Ph
68%
Nar
asak
a C
hem
Let
t. 19
89, 2
169
HO
Ph
OT
BS Ph
+2.
5 M
n(pi
c)3
DM
F, 0
˚C
, 2h
89%
Ph
Ph
OO
Nar
asak
a C
hem
Let
t. 19
91, 1
193
MeO
2C
O
Me
2 M
n(O
Ac)
3
AcO
H, r
tC
u(O
Ac)
2
O
MeO
2CM
e
86%
2 M
n(pi
c)3
AcO
H, r
tC
u(O
Ac)
2
O
MeO
2C
MeM
e
15%
Mn(
pic)
3 an
d M
n(O
Ac)
3 be
have
diff
eren
tly in
ace
tic a
cid:
Sni
der
J. O
rg. C
hem
. 199
3, 5
8, 6
217
24-M
n pi
colin
ate
4/13
/99
11:2
7 A
M
H
Mn
(pic
) 3:
Oxi
dat
ive
Rin
g E
xpan
sio
n
HO
OT
BS Ph
+2.
4 M
n(pi
c)3
DM
F, 0
˚C
O
O
Ph
+
OO
Ph
77%
5%
HO
OT
BS Ph
+2.
4 M
n(pi
c)3
DM
F, 0
˚C
O H
HO
Ph
n=1
81%
n=2
63%
( )
n(
)n
H
HO
H
H
HO
H
HO
H
Nar
asak
a B
ull C
hem
. Soc
. Jpn
. 199
9, 7
2, 8
5
Cyc
lizat
ion
sele
ctiv
ity is
con
sist
ent
with
the
Bec
kwith
-Hou
k m
odel
>9:
1
"boa
t""c
hair"
25-M
n pi
colin
ate
ring
xpan
sion
4/27
/99
2:02
AM
Oxi
dat
ive
Rin
g E
xpan
sio
n:
S
ynth
esis
of
10-I
soth
iocy
anat
og
uai
a-6-
ene
Nar
asak
a B
ull C
hem
. Soc
. Jpn
. 199
9, 7
2, 8
5
O OH
1) D
HP
, PP
TS
2)
CuB
r•S
Me 2
,T
MS
Cl
MgB
r
83%
OT
MS
OT
HP
1) E
t 2Z
n, C
H2I
2
2) K
2CO
3, M
eOH
OH
OT
HP
81%
, 10:
1
Mn(
pic)
3, n
-Bu 3
SnH
DM
F, 0
˚C
76%
, >9:
1
O
HM
e
TH
PO
HM
e
Me S
CN
10-I
soth
iocy
anat
ogua
ia-6
-ene
26-M
n pi
colin
ate
Gua
iano
lide
4/27
/99
2:01
AM
Oxi
dat
ive
Rin
g E
xpan
sio
n:
Syn
thes
is o
f (-
)-M
eth
yl C
anta
bra
die
nat
e
Sni
der
J. O
rg. C
hem
. 19
94, 5
9, 5
419
H3C
NC
O2t
-Bu
t-B
u
MgB
rH
3C1) 2)
PD
C
55%
CO
2H
CH
3
20:1
oxal
yl c
hlor
ide
DM
AP
, DIP
EA
,to
luen
e, ∆
79%
H3C
H
CH
3O
ED
TA
•Li
1:1,
79%
H3C
H
CH
3
HO
Mn(
OA
c)3
Mn(
pic)
3
46%
58%
H3C
H
CH
3H
2C
O
1) K
HM
DS
, PhN
(Tf)
2
2) P
dCl 2
(PP
h 3) 2
DIP
EA
, CO
, MeO
H
3) C
H2N
2
H3C
H
CH
3H
2C MeO
2C45
%(-
)-m
ethy
l can
tabr
adie
nate
7 s
teps
, 9%
ove
rall
yiel
d
OH
O
CH
2
Mn(
III)
27-M
n pi
colin
ate
Sni
der
4/24
/99
7:10
PM
Ref
lect
ion
s o
n M
n(I
II)
Impo
rtan
t in
the
synt
hesi
s of
fuse
d- a
nd b
ridge
d- p
olyc
yclic
nat
ural
pro
duct
s, o
ften
exhi
bitin
g
e
xcel
lent
reg
iose
lect
ivity
in c
ycliz
atio
ns
Mn(
OA
c)3
is a
uni
que
one-
elec
tron
oxi
dant
for
acid
ic C
-H b
onds
Lia
bilit
y: p
olym
eriz
atio
n an
d ot
her
side
-rea
ctio
ns o
ften
lead
to m
odes
t yie
lds
Mn(
pic)
3 of
fers
inte
rest
ing
rout
es to
nat
ural
pro
duct
s by
oxi
dativ
e cy
clop
ropa
ne fr
agm
enta
tion
28-c
oncl
usio
n4/
27/9
91:
13 A
M
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