Hypervalent Iodine
Julian Lo
1. Introduction
Hypervalent refers to a main group element that breaks the octet rule and formally
has more than 8 electrons in its valence shell
Iodine(III)
Cl
I Cl
O
AcO I OAc
iodobenzene
dichloride
O
I
O OH
2-iodoxybenzoic
acid (IBX)
(bisacetoxyiodo)benzene
(PIDA, BAIB)
O
O
I OAc
AcO OAc
Dess-Martin
periodinane (DMP)
Iodine(VII)
"
I
O
I
O
"
I
O
Ph
Ph
I
O
I
O
Ph
iodosylbenzene
sodium
periodate
L–I–L bond consists of an unhybridized p orbital
2 e- come from iodine and 1 e- comes from
each L, creating a 4 e-, 3 center bond
bonding
L
δ-
I
δ+
Negative charge accumulates on each L,
positive charge accumulates on central I
L
δ-
Martin–Arduengo nomenclature
[N-X-L]
number of
valence e-
central
atom
Aryl-λ3-iodanes
(ArIL 2)
Ar–I bond is a typical
bond with sp2 hybridization
number of
ligands
Aryl-λ5-iodanes (ArIL 4)
2.3–2.7 Å
L
vs.
I
Ar
I–L bonds are the hypervalent
bonds
L
Ar
I
L
[10-I-3]
The most electronegative ligands reside in the
apical (axial) positions
Ar
L
L
I
Ar
Ar
[10-I-3]
[8-I-2]
"X-ray structural data for the overwhelming
majority of iodonium salts show a significant
secondary bonding between the iodine atom and
the anion." (Zhdankin, Chem. Rev. 2008, 5299.)
L
L
I
Two orthogonal
hypervalent L–I–L bonds
with each using an
unhybridized p orbital
Ar–I bond is a typical bond
with sp hybridization
[12-I-5]
Most electropositive substituent
resides in the apical position
General reactivity
Iodine(III) reactivity depends on the ligands attached
Iodine(V) and iodine(VII)
L
I L
R I L
vs.
R
R
Oxidative processes R group transfer
Oxidative processes
2. Basic mechanisms
Ligand exchange
The hypervalent molecular orbitals
nonbonding
L
O
O I O
O Na
n
antibonding
Diaryl-λ3-iodanes vs.
diaryliodonium salts (Ar 2IL)
Ar
Iodine(V)
Baran Group Meeting
6/15/13
Kajigaeshi, Tetrahedron Lett. 1988, 5783.
Can theoretically proceed through either an
associative or dissociative mechanism
ICl 3
BnMe 3NCl
Tetracoordinated species have been isolated,
suggesting an associative mechanism
Cl
Cl
DCM
I
Cl
Cl BnNMe 3
Reductive elimination
Kitamura, J. Am. Chem. Soc. 1999, 11674.
Driven by reduction to return to univalent
iodide and by an increase in entropy
TMS
Leaving group ability 10 6 times greater
than OTf, making it a "hypernucleofuge"
(reason why alkyl-λ3-iodanes are so rare)
TBAF
IPh(OTf) DCM, rt
+ PhI
+ TMSF + TBAOTf
Configurational isomerization
Can occur via intramolecular ligand exchange or Berry pseudorotation (Ψ)
X
I
Y
Ψ
Ar
X
I
YAr
X
I
Ar Y
Y
I
Ar
Y
X
Ψ
Ψ
I
X
Ar
Hypervalent Iodine
Julian Lo
Baran Group Meeting
6/15/13
3. Not covered (extensively)
4. α-Functionalizations
Basic oxidations of alcohols to the corresponding carbonyl compounds
⋅Can oxidize allylic alcohols to enals with IBX and do Wittigs in one pot
(Yadav, Synth. Commun. 2001, 149)
Direct α-oxytosylation of ketones.
Koser, J. Org. Chem. 1982, 2487.
Oxidative cleavage of diols using PhI(OAc) 2, DMP, NaIO 4, ect.
Me
Me
O
CF3 transfer reagent and potentially explosive
Waser, J. Chem. Commun. 2011, 102.
Haller, J. Org. Process. Res. Dev. 2013, 318.
O
I
O
IBX
Nicolaou,
Nicolaou,
Nicolaou,
Nicolaou,
OH
Mixtures of DMP and Ac-IBX (hydrolyzed
O
DMP) oxidizes N-aryl amides, ureas, and
I OAc
carbamates to the o-imidoquinones
AcO OAc
DMP
Nicolaou, J. Am. Chem. Soc. 2002, 2212.
Nicolaou, J. Am. Chem. Soc. 2002, 2221.
I OH
O
H 3O+
OH
Ar
R'
40–70%
MeO OMe
OH
MeOH, KOH
(OC) 3Cr
(OC) 3Cr
O
O
O
I O
O
OMe
I Ph
(OC) 3Cr
[4+2]
O
hetero
[4+2]
MeO OMe
OH
Ar
R'
KOH,
MeOH
Proceeds via SET
IBX proposed to be
activated prior to SET:
O
Ph
Oxygenation installed on more hindered face.
Moriarty, J. Org. Chem. 1987, 153.
O
PhI(OAc) 2
Benzylic oxidation
Oxidation to α,β-unsaturated carbonyl compounds
Oxidation of silyl enol ethers in conjunction with MPO
Cyclization of N-aryl amides, ureas, and carbamates
J. Am. Chem. Soc. 2002, 2245.
J. Am. Chem. Soc. 2000, 7596.
J. Am. Chem. Soc. 2002, 2233.
Angew. Chem. Int. Ed. 2002, 996.
R'
Ar
Togni's reagent
O
Me
OTs
(PhIO)n or
PhI(OAc) 2
O
Me
Me
O
Me
α-Hydroxylation of ketones.
Moriarty, Tetrahedron Lett. 1981, 1283.
Transition metal–catalyzed cross coupling processes where an aryl, alkenyl, or
alkynyl iodoinum salt serves as the organohalide
I
Me
Silyl enol ethers and silyl ketene acetals can also be used as the nucleophile
Reactions where PhI(OAc) 2 or similar reoxidizes a transition metal in a catalytic cycle
F 3C
Me
MeCN, Δ
94%
Halogenations using TolIF2, PhICl 2, ect.
via:
O
PhI(OH)OTs
O
[O]
N
R'
O
o-Imidoquinone reactivity
O
(OC) 3Cr
(OC) 3Cr
R
MeO
MeO O OMe
I Ph
Used in the total synthesis of cephalotaxine.
Hanaoka, Tetrahedron Lett. 1986, 2023.
O
O
O
O
N
O
H
O
(PhIO)n
KOH,
MeOH
(79%)
N
O
H
HO
MeO OMe
O
N
O
H
HO
OMe
(±)-cephalotaxine
Hypervalent Iodine
Julian Lo
α-Oxidations of ketones can also occur under catalytic conditions.
Ochiai, J. Am. Chem. Soc. 2005, 12244.
product
mCPBA
PhI
mCPBA,
O
O
PhI (10 mol %)
AcOH
R'
R'
R
PhI(O 2CR) 2
O
BF 3•Et 2O,
R
OAc
AcOH, H 2O
R'
OH
43–63%
R
R'
IPh(OAc)
R
Coupling of carbon nucleophiles.
Zhdankin, J. Org. Chem. 1989, 2605.
OTMS
Ar
(PhIO)n
HBF 4
O
I(BF 4)Ph
-78 °C
δ+
δ-
E
major product
Me
Ar
NO 2
Ar
O
O
But:
(81%)
OTMS Ph IF
2
O
Ph
Ph
(51%)
(89%)
O
NBoc 2
IPh(BF 4)
CO 2Me
+
O
N
H
Me
Me
N
IPhF
2. AgF
NO 2
N
H
Me
CO 2Me
tabersonine
Me
Ph
Me
N
Ph
Li
(2 equiv.)
2. 2
(41%, 94% ee
d.r. >20:1)
Cl
O
H
N
N
Cl
N
NBoc 2
(–)-epibatidine
A mechanistic study reveals that the more electron deficient aryl
group migrates in unsymmetrical salts.
Ochiai, ARKIVOC 2003, 43.
OK
N
α-Arylation in a more modern setting.
Aggarwal, Angew. Chem. Int. Ed. 2005, 5516.
1.
Phenylation of silyl enol ethers.
Koser, J. Org. Chem. 1991, 5764.
Ph
MeO 2C
1
(50%)
Ph 2IF
O 2N
1. K 2S2O8,
H 2SO 4, KI
I
O
O
O
CO 2Me
(94%)
OTMS
OTMS
+
Used in the synthesis of the indole core of tabersonine.
Rawal, J. Am. Chem. Soc. 1998, 13523.
MeO 2C
MeO 2C
TiCl3,
N
N
NH 4OAc
1
O
(63%)
I
Ph
I
TBSO
Ar
TMS
O
Ar
O
O
O
(90%)
Baran Group Meeting
6/15/13
Li
O
O
ICl 2 Cl
ICl 3
I
E
HCl
(21%)
Cl
Cl
I
N
(~70%)
Cl
N
2
N
Cl
Hypervalent Iodine
Julian Lo
Enantioselective aziridination.
Evans, J. Am. Chem. Soc. 1993, 5328.
Evans, J. Am. Chem. Soc. 1994, 2742.
5. Azidonation, aziridination, and amination
(Di)azidonation of silyl enol ethers.
Magnus, J. Am. Chem. Soc. 1992, 767.
OTIPS
OTIPS
(PhIO)n
TMSN3
N3
I N3
Ph
(2 equiv.)
-15 °C
TIPSO N 3
Ar
β-Azidonation pathway:
OTIPS
-N 3
N3
PhI=NTs
CuOTf
(10 mol %)
Ar
Azidonation of N,N-dimethylanilines.
Magnus, Synthesis 1998, 547.
R
TMSN3
NMe 2
+
MeO
OTBS
Ph
Me
N
via:
Me
N
N3
R
O O
S
O
NH 2
MeN
Ph
OTBS
TMSN3
N
N
Ts
60–76%
94–97% ee
N
Ph
Ph
3
NTs
H
Ar
Cl
H
N
N
R
Cl
Cl
Cl
4
DuBois' nitrene chemistry proceeds through an iminoiodinane.
DuBois, Tetrahedron 2009, 3042.
R
(PhIO)n
O
OR
50–79%
58–98% ee
Ph
PhI(OAc) 2
-2 AcOH
O O
[Rh] cat.
S
I
O
N
Ph
O O
S
[Rh]
O
N
Ph
O O
S
O
NH
Ph
Ph
MeO
Aryl C–H insertions can take place without the presence of transition metals.
Tellitu, J. Org. Chem. 2005, 2256.
Substrate controlled amination of allyl silanes.
Panek, J. Am. Chem. Soc. 1997, 6040.
O
Rationale:
R'
R
PhI=NTs
OH
DMPS
But:
4
(11 mol %)
R
(PhIO)n
Ar
O
An alternative ligand for enantioselective aziridination.
Jacobsen, J. Am. Chem. Soc. 1993, 5326.
OTIPS
H
Me
N
Me
3
(6 mol %)
OR
Me Me
O
N 3 via radical
addition
-45 °C
OTIPS
Ph
I
N3
PhI=NTs
CuOTf
(5 mol %)
O
N3
TEMPO
(cat.)
Baran Group Meeting
6/15/13
CuOTf
(10 mol %)
OMe
Me
OTBDPS
DMPS
R'
TsN
PhI=NTs
CuOTf
(10 mol %)
OH
R
MeO
DMPS
H
R'
60–65%
> 30:1 de
H
R
O Cu
H NTs
OTBDPS
Me
64%
2:1 ds
N
HN
MeO
O
PhI(O 2CCF3) 2
CF3CH 2OH
(70%)
TsN
R
R'
OH
DMPS
N
MeO
N
MeO
O
O
O
MeO
OMe
TsN
MeO
O
MeO
MeO
N
N
H
H
O
Mo(CO) 6, Δ
MeO
(76%)
MeO
N
N
MeO
H
O
Hypervalent Iodine
Julian Lo
6. Oxidative dearomatization of phenols
There are several possible mechanisms.
Quideau, Tetrahedron 2010, 2235.
Can also be used in conjuction with 1,3-dipolar cycloadditions.
Sorensen, Org. Lett. 2009, 5394.
Me OTBS
O
R
Dissociative
OH
N
Nuc
-PhI -AcOPh
OH
O
HO
OAc
I
-AcOR'
O
-PhI
-AcO-
R'
O
Nuc
R
R'
O
cortistatin A
And Diels-Alder reactions.
Danishefsky, J. Am. Chem. Soc. 2006, 16440.
OH
OH
IPh(Nuc)
OBn PhI(OAc)
Me
I
Me
OTs
HN
NP
ArSO2NH
N
H
Br
N
(25%)
O
NH
Br
N
HN
ArSO2NH
O
O
Me
Me
CO 2Me
O
HO H
Me
O
OBn
O
Me Me
OTs
µW
(65%)
O
O
OH
HO
Me O
Me
(±)-11-O-debenzoyltashironin
Me
OBn
Me OTs
IBX can directly oxidize electron–rich phenols to o-quinones.
Pettus, Org. Lett. 2002, 285.
O
Me
Me
OTBS
H
Oxidative dearomatization often initiates cascade sequences (eg. diazonamide A).
Harran, Angew. Chem. Int. Ed. 2003, 4961.
Me
Me
Me
Me
O
O
ArSO2NH
ArSO2NH
N
N
N
N
CO 2Me
CO 2Me
H
H
PhI(OAc) 2
O
O
N
H
Me
O
2
R'
O N
O
Nuc
-PhI
R'
LiOAc,
CF3CH 2OH,
-20 °C
OTBS
H
?
OH
IPh(Nuc)
R
R
Me
O
R
O
R'
OH
N
rt to 50 °C
(80%)
H
or
-PhI
IPh(Nuc)
A radical pathway
has also been
proposed.
O
O
O
R'
+Nuc
-AcO-
Ligand
coupling
PhI(OAc) 2,
CF3CH 2OH
R'
Nuc
R Associative
R PhI(OAc)
2
Baran Group Meeting
6/15/13
CO 2Me
H
O
HO
R
R'
O
O
Br
NH
Br
IBX
DMF
O
R
O
R'
HO
OMe
O
O
I
O
O
R
R'
AcO
Ac2O,
K 2CO3
(76%)
20–99%
Authors propose:
O
IBX, H 2,
Pd/C
O
I
OMe
AcO
O
R
O
R
O
R'
O
R'
Hypervalent Iodine
Julian Lo
The use of oxidative dearomatization can be more subtle.
Pettus, Org. Lett. 2005, 5841.
HO
HO
OH
IBX;
BnO
O Na 2S2O 4
(58%)
HO
PhI(O 2CCF3) 2
BnO
HO
(±)-brazilin
H2
HO
O
OH
O
O
OH
BnO
O
OH
HO
O
H
O
OH
iPr 2NEt,
LiI
(81%)
O
Pd/C
OBn
OBn
Possible involvement of CT complex in dimerization of indoles at the 2 position?
Kita, Org. Lett. 2006, 2007.
Me H
Me H
Me
PhI(O 2CCF3) 2,
N
N
TMSBr
+
DCM
N
N
N
-78 °C to -40 °C
H Me
H Me
H
74%
29%
Application of charge transfer chemistry in total synthesis.
Kita, Synthesis 1999, 885.
PhI(O 2CCF3) 2,
Br
Br
BF 3•Et 2O, DCM;
S
BnO
MeNH 2
S
BnO
Bn
(66%)
N3
7. Aryl charge transfer complexes
Nucleophilic substitution can also occur on para-substituted aryl ethers via a charge
transfer complex.
Kita, J. Am. Chem. Soc. 1994, 3684.
OMe
OMe
OMe
CF3CO 2
Nuc
PhI(O 2CCF3) 2
SET
Nuc
Ph I O 2CCF3
(CF 3) 2CHOH
SET
or CF3CH 2OH
MeO
R
R
R
R
Nuc = TMSN3, TMSOAc,
1,3-dicarbonyls
OMe
MeO
MeO
-40 °C
(91%)
MeO
N
Ts
BF 3•Et 2O
(83%)
N
Ts
CN
S
Me
Me
BF 3•Et 2O
(79%)
Me
S
CN
N
H
Br
OH
makaluvamine F
O
Me
Me
Me
PhICl 2
I
Me
Me
Br
CBr 4,
hν
O
I
O
A variant of the Hofmann-Löffler-Freytag reaction.
Suárez, Tetrahedron Lett. 1985, 2493.
Me
Me
Me PhI(O 2CCF3) 2
TMSCN
N
H
O
O
8. Radical processes
H
Can also be used to add nucleophiles to heterocycles.
Kita, J. Org. Chem. 2007, 109.
S
MeO
O
MeO
PhI(O 2CCF3) 2
TMSCN
(CF 3) 2CHOH,
H 2O
(51%)
Me
Intermolecular version
uses C6F 5I(O 2CCF3) 2,
gives no homocoupling.
Kita, Org. Lett. 2011, 6208.
HN
Remote steroidal C–H functionalization.
Breslow, J. Am. Chem. Soc. 1991, 8977.
Me
Me
MeO
PhI(O 2CCF3) 2
BF 3•Et 2O
N
Ac
HN
N
PhI(O 2CCF3) 2,
TMSOTf
MeO
Intramolecular biaryl coupling of electron–rich aryl ethers.
Kita, J. Org. Chem. 1998, 7698.
MeO
Baran Group Meeting
6/15/13
Me H
N EWG
Me
Me
PhI(OAc) 2,
I2
Me
Me
C6H12, Δ
(77%)
Me
N
EWG
Me
Hypervalent Iodine
Julian Lo
Suárez conditions can also generate alkoxy radicals.
Pattenden, Tetrahdron Lett. 1993, 127.
HO
PhI(OAc) 2
I 2, h υ
(58%)
H
O
H
Me
H
O
O
PhO 2S
I
Me
PhI(OAc) 2
H
En route to (+)-epoxydictymene.
Paquette, Tetrahedron Lett. 1997, 195.
Me
H Me PhI(OAc) 2,
Me
I2
H
Me
C6H12, Δ
HO
H
(95%)
OAc
O
- 2 AcOH
EtO
tBuOO
H
Et 2O
Me
EtO
Me
H
O
-PhI
2 tBuOO
tBuOOOOtBu
tBuO + tBuOO
tBuOOOtBu
-5 °C
to 5 °C
O
OtBu
EtO
Me H
O O
I
Me
H
H
OMe
Me
O
O
OR
HO
I
O
tBuOO
TBHP
O
H
O
MeO
Me
Me
Me
I
Cs 2CO3
O
OR
(10–76%)
O
BF 3•Et 2O
(90%)
Ar
O
OR
PhI(O 2CR) 2 can be decarboxylated to give radicals.
Togo, J. Chem. Soc. Perkin Trans. 1 1993, 2417.
Me
Me
O
PhI(O 2CCF3) 2
+
h υ or Δ
R
OH
(13-88%)
N
R
N
R = alkyl, RC(O)
Similar reaction can perform C–H amidation.
Zhdankin, Tetrahedron Lett. 1997, 21.
O
HO I
O
TMSOTf;
R
N I
O
H
RC(O)NH 2,
pyr
(63–75%)
H Me
NP
OR
Allylic oxidation of alkenes to enones.
Yeung, Org. Lett. 2010, 2128.
O
Me
H
OAc
Me
Radical generation:
PhI(O 2CR) 2
R
-CO2
H
AcO
PhCl, Δ
(PhCO 2) 2
cat.
N
H
R = p-ClC 4H 6 (58%)
Me
H
H
O
H
AcO
PhI(OAc) 2,
TBHP, K 2CO3
RCO 2
O
O
Me
PhI(OAc) 2,
TBHP, K 2CO3
nPrCO 2nBu
0 °C
(81%)
H
H
h ν or Δ
-PhI
Me
nPrCO 2nBu
-20 °C
(84%)
O 2N
O
O
Ar
(21–84%)
H
O
tBuOOtBu
+ O2
+ tBuOH
K 2CO3
H
-1 /2 O 2
-75 °C to
-65 °C
A stable (alkylperoxy)iodane that oxidizes allyl and benzyl ethers.
Ochiai, J. Am. Chem. Soc. 1996, 7716.
H
O
O
O
PhI(OOtBu) 2
- tBuOH
PhO 2S
H
O
O
TBHP,
-80 °C
H
O
MeO
H
H
(58%)
β-Fragmentation paths can also lead to 2-dioxolanes.
Suárez, J. Org. Chem. 1998, 4697.
H
Me
PhO 2S
1. PhI(OAc) 2,
H
PhO 2S
I 2, h ν
O
2. NaOMe
O
OH H
(79%)
PhO 2S
TBHP undergoes a complicated decomposition pathway in the presence of PhI(OAc) 2.
Milas, J. Am. Chem. Soc. 1968, 4450.
Me
O
Baran Group Meeting
6/15/13
Authors propose:
O
R
RO
TBHP
O
RO
PhI(OAc) 2
R'
O 2N
R'
tBuOO
I
O
Ph
+ tBuOO
n
Me
Hypervalent Iodine
Julian Lo
Oxidation of unactivated C–H bonds.
Yeung, Org. Lett. 2011, 4308.
O
PhI(OAc) 2,
TBHP(aq.)
O
R
Proposed intermediate:
X
O
R
MeCN
(32–56%)
O
R
X
Shown to not proceed through the originally proposed α-carbon attack (13C labeling).
Ochiai, J. Am. Chem. Soc. 1986, 8281.
ONa
n-C6H13
O
tBuOO
I OOtBu
Ph
O
PhIO
NaBF 4
Et 2O•BF 3
DCM, rt
H 2O
R
DCM,
0 °C
R
OTf OTf
I O I Ph
R
O
n-C8H17
I BF 4
Ph
n-C6H13 BF 4
O
n-C5H11
Ph
(84%)
O
n-C5H11
O
SnBu3
TMS
O
R
I OTf
Ph
DCM, 0 °C to rt
DCM
EWG
I OTf
Ph
-42 °C
ONa
Provides a route to amino cyclopropanes.
Lee, Synlett 2001, 1656.
nBuLi;
I Cl
Ph
Me
IPh(OTs)
HCl
(76%)
Me
Me
N
Ts
N
Ts
O
NHTs
With a cascade ending with a formal Stevens shift.
Feldman, Org. Lett. 2000, 2603.
IPh(OTf)
O
+
Ph
Ph
Alkynylation of of nucleophiles with alkynyl(aryl) iodonium salts.
Beringer, J. Org. Chem. 1965, 1930.
Ph
n-C6H13
O
+
TfO I CN
+
Ph
Ph
I
O
NHTs
SnBu3
O
Ph
O
Ph +
I BF 4
Ph
For electron poor alkynes.
Stang, J. Am. Chem. Soc. 1994, 93.
EWG
O Ph
H
or
Ph
I BF 4
Ph
ONa
For R = TMS or alkyl.
Stang, J. Org. Chem. 1991, 3912.
Tf2O
Ph
Can be utilized in a conjugate addition–carbene insertion cascade.
Ochiai, J. Am. Chem. Soc. 1986, 8281.
For R = alkyl or Ph.
Fujita, Tetrahedron Lett. 1985, 4501.
PhIO
O
O
Although not commerically available, there a many ways to synthesize.
TMS
Ph
+
n-C6H13
9. Alkynyl(aryl)-λ3-iodanes
R
Baran Group Meeting
6/15/13
Ph
Ph
(73%)
O
TolSO2Na
O
O
O
O
TolO2S
O
O
TolO2S
41%
O
+
TolO2S
27%
Hypervalent Iodine
Julian Lo
Used in key step of pareitropone synthesis.
Feldman, J. Org. Chem. 2002, 8528.
OTIPS
IPh(OTf)
MeO
MeO
10. Alkenyl(aryl)-λ3-iodanes
OTIPS
NH
MeO
S
I
Ph
R'
[3,3]
H
N
R
R'
O
MeO
NTs
N
MeO
pareitropone
R
IPh(BF 4) Bu NOAc
4
S
32–62%
H
N
60 °C
R'
R'
S
N
R
IPh
O
1. NaIO 4, AcOH, H 2O
TIPS
I
Me
tBuOK
IPh(BF 4)
-78 °C
(61%)
O
N
H
AuCl
(1–5 mol %)
R
N
H
(48–93%)
Me
H
O
Ph
Ph
Ph
Ph
Ph
(90%)
Ph
Direct SN 2 reaction of vinyliodonium salts and isotopic labeling studies provide
evidence for β-elimination.
Ochiai, J. Am. Chem. Soc. 1991, 7059.
R
nBu 4NX
R
X + R
MeCN, rt
IPh(BF 4)
~85%
~15%
Mechanistically:
X
R
R
H
Ph
R
X
H
I
I Ph
Cl
Cl
R
TIPS
O
Pt(PPh 3) 2
tBuOK
S
H
Ph
Pt(PPh 3) 3
O
2. TMSOTf, pyr.
MeCN
TIPS
TMS
Can also use (benzo)thiophenes (need TFA).
Waser, Angew. Chem. Int. Ed. 2010, 7304.
NaBF 4
(80%)
O
Ph
Benziodoxoles in direct alkynylations of pyrroles and indoles.
Waser, J. Angew. Chem. Int. Ed. 2009, 9346.
OH
SnBu3
N
Counterintuitive regiochemical outcome in Diels–Alder reactions.
Stang, J. Org. Chem. 1997, 5959.
δ−
IPh(OTf)
(TfO)PhI
R
rt
(TfO)PhI
+
+
EWG
δ+
(68–84%)
R
EWG
R
EWG
major
minor
I
(PhIO)n,
BF 3•Et 2O;
R'
R
S
Me
β-Elimination can produce cyclohexyne.
Fujita, J. Am. Chem. Soc. 2004, 7548.
Cyclocondensation with thioamides to thiazoles.
Wipf, J. Org. Chem. 1996, 8004.
S
base
MsO I
R'
+
Ph
R
NH 2
R = Ar, C(O)R, NH 2
R' = Ph, nBu
R
Alkenyl iodonium salts can be synthesized analogously to the alkynyl iodonium salts
and undergo similar chemistry via base-induced alkylidinecarbenes.
Ochiai, J. Am. Chem. Soc. 1988, 6565.
KF/
Al2O3
MeO
NHTs
via:
O
LiNTMS 2
64%
Baran Group Meeting
6/15/13
R
H
Cl
I
Ph
-HCl
-PhI
R
(X = F proceeds via alkylidinecarbene)
Computationally, the σ* of the vinyliodonium
salt was found to be lower in energy than the π*.
(Okuyama, Can. J. Chem. 1999, 577)
Can also use: AcOH, DMF, ArSH, R 2S, R 2Se,
RC(S)NH 2
Hypervalent Iodine
Julian Lo
Mixed phosphonium–iodonium ylides.
Zhadankin, J. Org. Chem. 2003, 1018.
11. Iodonium ylides
Iodonium ylides as an alternative to α-diazo dicarbonyl compounds in intramolecular
cyclopropanations.
Moriarty, J. Am. Chem. Soc. 1989, 6443.
O
KOH,
MeOH
OMe
Authors propose:
PhI
O
I
Ph
O
OMe
Ph
O
iPr
O
[Rh 2{(–)-(S)-ptpa}4]
O
O
iPr
iPr
SO2Ph
iPr
PhO 2S
O
PhI(OAc) 2
IPh
O
O
Ph
O
MeCN,
hν
(96%)
IPh
MeI
DCM
(56%)
SO2Ph
Me
PhO 2S
I
SO2Ph
PhO 2S
Me
IPh MeI, DCM
rt
SO2Ph
PhO 2S
IMe
SO2Ph
PhO 2S
Me
34%
+
I
H
H
46%
SO2Ph
O
DCM, Δ
(84%)
O
O
OH
NHPh
O
O
SO2Ph
Me
PhO 2S
I
O
PhNH 2
Ph
Me
Me
SO2Ph
PhO 2S
O
OH
IPh
SO2Ph
Iodonium ylides can also undergo Wolff rearrangements.
Spyroudi, J. Org. Chem. 2003, 5627.
O
Br
Intermolecular transylidation can generate reactive alkyl iodonium ylides.
Hadjiarapoglou, Synlett 2004, 2563.
Ph
X = N 2 (89%, 69% ee)
X = IPh (78%, 67% ee)
Iodonium ylides perform the same chemistry
as the corresponding diazo species
(albiet in slightly lower yields).
Me
MeOH, 0 °C
(81%)
O
Me
Me
OMe
O
X
Me
IPh(OTs)
Ph 3P
Iodonium ylides undergo a net 1,3-dipolar cycloadditions upon photolysis.
Hadjiarapoglou, Tetrahedron Lett. 2000, 9299.
MeO
I
Ph
O
KBr
Can also use PhSLi and PhSO 2Na
Transition metal–catalyzed iodonyl ylide chemistry proceeds through metal carbenoids.
Müller, Helv. Chim. Acta. 1995, 947.
O
DCM
(50%)
O
O
Ph 3P
O
O
O
Me
H
H
O
PhI(OH)OTs
O
(90%
overall)
OMe
O
Ph 3P
H
Cu(I) or
Cu(II)
O
PhI(OAc) 2
O
Baran Group Meeting
6/15/13
H
SO2Ph
SO2Ph
SO2Ph
I
H Me
SO2Ph
I
H Me
H
SO2Ph
SO2Ph
I
H Me
H
Hypervalent Iodine
Julian Lo
A mechanistic controversy arising from an I to O Ph migration.
Nozaki, Tetrahedron 1970, 1243.
Me Me
via: Me Me
Me Me
O
pyr
O
O
I
O
O
Bakalbassis, J. Org.
Chem. 2006, 7060.
Me Me
Tol
O
Tol
I O
I
O
O
I Tol
O
O
O
Me
Me
I
Me Me
L
Me
R
-78 °C
R'
O
O
>-30 °C
IPh
unstable
R
Br
O
R
N
EWG
vs.
Ph
I
O
O
stable
I
O
OAc
Reaction can also be ran catalytically with
mCPBA as the stoichiometric oxidant and
AcOH as an additive: gives 70% with 69% ee
5
An alternative, conformationally flexible iodoarene catalyzes the same reaction.
Ishihara, Angew. Chem. Int. Ed. 2010, 2175.
O
6
OH
OH
I
O
(10 mol%),
O
Me
O
O
Me
mCPBA
O
*
(59–92%
HN
O
O
NH
83–90% ee)
6
R
Mes
Mes
R
Proposed active oxidant:
O
LO
I
O
L
O
NHMes
O
Me
or
Me
Mes
N H
O
I
L
Mes
L H N
O
O
Me
R'
O EWG
N
R
OAc
I
R
Me
IPh
R
-30 °C
(39–81%)
O
O
O
-30 °C
(51–92%)
O
EtOLi
IPhBr
R'
O
O
*
(81–86%
80–86% ee)
MesHN
Monocarbonyl iodonium ylides.
Ochiai, J. Am. Chem. Soc. 1997, 11598.
Ochiai, J. Org. Chem. 1999, 3181.
O
5
(0.55 equiv)
O
Me
Me
Me Me
AcO
OH
R
Moriarty, J. Org. Chem. 2005, 2893.
R
OH
I
Me
O
Chiral 1,1'-spirobiindane iodine(III) reagent dearomatizes phenols enantioselectively.
Kita, Angew. Chem. Int. Ed. 2008, 3787.
O
I
Δ
Baran Group Meeting
6/15/13
R'
Secondary bonding
responsible for stability?
Varvoglis, Acta Crystallogr.,
Sect. C: Crystal Structure
Commun. 1990, 1300.
12. Chiral iodanes for enantioselective transformations
A related lactate–derived reagent promotes and "enatiodifferentiating endo-selective
oxylactonization."
Fujita, Angew. Chem. Int. Ed. 2010, 7068.
AcO
OAc
I(OAc) 2
7 (1.5 equiv.),
R
R
Me
O
O
Me
AcOH
+
O
O
BF 3•Et 2O,
CO 2R'
O
OMe MeO
O
-80 to -40 °C
7
O
O
3–8%
57–88%
6–51% ee
75–96% ee
via:
AcO
OAc OAc
I Ar
AcO
I
R
Ar
R
CO 2R'
CO 2R'
Hypervalent Iodine
Julian Lo
13. Miscellaneous reactivity
Room temperature benzylic oxidation using catalytic iodine.
Zhdankin, Chem. Eur. J. 2009, 11091.
Ru(III)
Oxone
PhI (5 mol %)
O
RuCl (0.16 mol %)
PhIO 2
Ar
O
R
3
Ar
R
Ar
Oxone
MeCN, H 2O
R
Ru(V)
O
23–95%
Utilization of allenyl iodanes in propargylations.
Ochiai, J. Am. Chem. Soc. 1991,1319.
Ochiai, Chem. Commun. 1996, 1933.
R'
R'
I(OAc) 2
AcO I
TMS
R
BF 3•Et 2O
MgSO 4
-20 °C
Ar
R''O
or
R
Ar
PhIO
R
I
[3,3]
-20 °C
Ar
R
R'
ipso and meta
propargylation if
ortho positions are
both substituted
If R = m-NO2
R''OH or MeCN
(100 equiv.)
AcHN
One last application of hypervalent iodine in total synthesis.
Moriarty, J. Med. Chem. 1998, 468.
Ph
Ph
PhI(OAc) 2
PhI(OAc) 2
KOH,
MeOH
(40%)
O
O
CO 2Me
CO 2H I 2, AIBN
(92%)
PhI(OH)OTs
(90%)
NH 2
(22%)
Br
CONH 2
O
Br
K 2CO3
N
(analog)
I
Baran Group Meeting
6/15/13