IRON(III) CHLORIDE 1
MeO OMe
Iron(III) Chloride1
1. (CF3CO)2O
HO OH
2. FeCl3
FeCl3
N
MeO OMe
H
[7705-08-0] Cl3Fe (MW 162.20)
(3)
HO O
InChI = 1/3ClH.Fe/h3*1H;/q;;;+3/p-3/f3Cl.Fe/h3*1h;/q3*-1;m
N
InChIKey = RBTARNINKXHZNM-VBTRCSEMCV
O CF3
(mild oxidant capable of phenolic coupling,1 dimerizing aryl-
lithiums6 and ketone enolates;7,8 mild Lewis acid: catalyzes ene
reactions,21 Nazarov cyclizations,18-20 Michael additions,24 and HO HO
FeCl3
(4)
acetonations29)
NH2
N
MeO MeO
Alternate Name: ferric chloride. H
ć%
Physical Data: mp 306 C; d 2.898 g cm-3.25
Solubility: 74.4 g/100 mL cold water, 535.7 g ml-3 boiling water;
O
FeCl3, AcOH
ć%
v sol alcohol, MeOH, ether, 63 g mL-1 in acetone (18 C).
O (5)
NHOAc CH2Cl2
N
Form Supplied in: black crystalline powder; widely available.
75%
H
Preparative Methods: anhydrous FeCl3 available commercially
is adequate for most purposes. However, the anhydrous mate-
MOMO OBn
rial can be obtained from the hydrate by drying with thionyl
OMe
chloride7 or azeotropic distillation with benzene.12 FeCl3
OTBDPS
Handling, Storage, and Precautions: is hygroscopic and corro-
63%
MeO
sive; inhalation or ingestion may be fatal. It causes eye and skin
MOMO OBn
Li
irritation. It should be stored and handled under an inert dry
OMe
atmosphere.36 Use in a fume hood.
OTBDPS
MeO
(6)
MeO
OTBDPS
Original Commentary
OMe
MOMO OBn
Andrew D. White
Parke-Davis Pharmaceutical Research, Ann Arbor, MI, USA
O
O
Oxidative Properties.1 FeCl3 oxidizes a wide array of func-
1. 2 equiv LDA
(7)
tionalities, such as certain phenols to quinones (eq 1), dithiols to O
O
2. FeCl3
disulfides (eq 2), and 2-hydroxycyclohexanone to 1,2-cyclohex-
anedione.1 Inter- and intramolecular oxidative dimerization of
aromatics gives rise to such products as magnolol, metacyclo-
phanes,1 and crinine alkaloids (eq 3).2 Phenolic ethylamines
Stereoselective cross-coupling of alkenyl halides with Grignard
and N-acetyloxyamides can be cyclized to indoles (eq 4)3 and
reagents is catalyzed by FeCl3 (45 83%) (eqs 8 and 9).10 Propar-
oxindoles (eq 5),4 respectively. Dimerization of aryllithium or
gyl halides also react to afford allenes.11 A study of FeIII cata-
Grignard reagents yields intermediates for cyclophane5 and pery-
lysts revealed that Tris(dibenzoylmethide)iron(III) was the most
lenequinone6 synthesis (eq 6). Inter-7 and intramolecular8 ketone
useful.12
enolates can be converted to 1,4-diketones (eq 7), and lithium salts
Br
of allylic sulfones afford 1,6-disulfones.9
(8)
MeMgBr
FeCl3
NH2Cl O
OH O
FeCl3, 30 °C FeCl3, 70 °C
Br
(9)
MeMgBr
94% 97%
FeCl3
O
OH
Alkylcyclopentanones can be dehydrogenated to cyclopen-
tenones, but Copper(I) Chloride is a better catalyst.13 Trimethyl-
(1)
silyloxybicyclo[n1.0]alkanes can be oxidatively cleaved,
O
O
providing a three-step method of ring expansion (eq 10).14
O
Cycloalkanones are cleaved with FeCl3/MeOH under O2 to
É-oxo esters; this reaction works best with flanking methyl
SH
FeCl3
groups (eq 11).15 Photooxidation of alkenes with FeCl3 can
CO2H S CO2H (2)
HS S
44
yield a variety of useful chloroketones depending on the starting
Avoid Skin Contact with All Reagents
2 IRON(III) CHLORIDE
material,16 and photoreaction of carbohydrates in pyridine
FeCl3,  23 °C
CHO
induces a selective C(1) C(2) bond cleavage, in contrast to Tita-
(16)
OTIPS
OTIPS 82%
nium(IV) Chloride (C(5) C(6) cleavage) (eq 12).17 FeCl3/EtOH
can also be used to disengage tricarbonyliron complex ligands.
O
FeCl3
1. FeCl3, DMF
OTMS
CO2Et
(10) CO2Et + Et2NH (17)
Et2N
96%
2. NaOAc
84%
In the field of protecting group chemistry FeCl3 will cleave
O
benzyl25 and silyl ethers,26 convert MEM ethers to carboxylic
O
FeCl3, O2
esters,27 and when dispersed on 3Å molecular sieves catalyzes
(11)
MeOH CO2Me the formation of MOM ethers.28 In the area of carbohydrate
93%
chemistry, FeCl3 is proving a versatile reagent for acetylation,
acetonation, acetolysis, transesterification, O-glycosidation of ²-
OH
per-O-acetates, formation of oxazolines, direct conversion of
1,3,4,6-tetra-O-acetyl-2-deoxy-2-acylamido-²-D-glucopyranoses
O O
1. h½, FeCl3
into their O-glycosides, preparation of 1-thioalkyl(aryl)-²-D-
OH
OH AcO OAc (12)
2. Ac2O
hexopyranosides from the peracetylated hexopyranoses having a
OH OHCO
OH OAc
1,2-trans configuration,29 and as an anomerization catalyst for
the preparation of alkyl-Ä…-glycopyranosides (eq 18).30
OBn OR
Lewis Acid Mediated Reactions. Silicon-directed Nazarov
1. FeCl3, CH2Cl2
BnO RO
cyclizations occur readily in dichloromethane catalyzed by FeCl3,
O O (18)
2. RCl, AgOTf
BnO OMe RO
utilizing the cation-stabilizing effect of silicon.18 Cyclohexenyl
90%
OBn ROOR
systems afford only cis-fused ring products. The reaction has
R = 4-MeOCinn
been elaborated to the preparation of linear tricycles with
²-silyldivinyl ketones at low temperature (eq 13).19 Optically
active ² -silyl divinyl ketones have been used to demonstrate that
Substituted amidines have been prepared from a nitrile
cyclization occurs with essentially complete control by silicon
compound, an alkyl halide, an amine, and FeCl3 in a one-pot
in the anti S sense.20 FeCl3 is the best Lewis acid catalyst for
E synthesis (40 80%) (eq 19).31 FeCl3 in ether converts epoxides
the intramolecular ene reaction of the Knoevenagel adduct from
into chlorohydrins. Fused bicyclic epoxides yield trans-chloro-
citronellal and dimethyl malonate at low temperature (eq 14).21 hydrins (eq 20).32 Friedel Crafts acylation of activated (Me,
However, the basic alumina supported catalyst can give more
OMe substituents) aromatics occurs readily with optically active
reliable results. The ene reaction of an unsaturated ester of an
N-phthaloyl-Ä…-amino acid chlorides catalyzed by FeCl3
ć%
allylic alcohol yields a chlorolactone cleanly at 25 C.22 This
(1 5 mol%).33 Trialkylboranes react with FeCl3 in THF/H2Oto
reaction produces only one of four possible diastereomers, with
afford alkyl chlorides in excellent yield.34 t-Alkyl and benzylic
clean trans addition to the double bond occurring (eq 15).
chlorides can be converted to the iodides on reaction with Sodium
1-Silyloxycycloalkanecarbaldehydes undergo ring expansion to
Iodide in benzene catalyzed by FeCl3.35
2-silyloxycycloalkanones (82 89%) (eq 16). FeCl3 catalysis pro-
NR2
vides the best selectivity derived from rearrangement of the more
H
N
substituted Ä…-carbon atom.23 FeCl3-catalyzed addition of primary
FeCl3
R1 N
R1CN + R2Cl + (19)
and secondary amines to acrylates occurs exclusively 1,4 with no
polymerization (79 97%) (eq 17).24
TMS O O
H
OH
1. FeCl3, Et2O
FeCl3,  50 °C
O (20)
(13)
2. H2O
79%
Cl
78%
H H
FeCl3, CH2Cl2
First Update
(14)
MeO2C 94% MeO2C
Fabrice Gallou
CO2Me CO2Me
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA
CO2Me CO2Me
O O
H
A number of applications of iron chloride in cross-coupling
FeCl3, CH2Cl2
CO2Me CO2Me
O O (15)
reactions has appeared recently as an alternative to more con-
85%
ventional organometallic catalysis with transition metals such as
H
Cl
palladium and nickel.
A list of General Abbreviations appears on the front Endpapers
IRON(III) CHLORIDE 3
OH
O
The stereoselective synthesis of 2-isopropyl 1,4-dienes through
the cross-coupling reaction of 2-benzenesulfonyl 1,4-dienes and Ph
PhMgBr (2 equiv)
OMe
OMe
isopropylmagnesium chloride can be mediated by iron salts to (24)
OMe
FeCl3 (0.1 equiv)
OMe
lead to the substitution of the sulfonyl group with stereoselectivity THF
25 °C, 16 h
higher than 96%. In addition, no isomerization of the isopropyl
then NH4Cl 62%
Grignard moiety to the n-propyl derivative is observed. A notable
limitation of the method is the significant amount of reduction of
the sulfonyl group (eq 21).37 Iron chloride has been used with 3-alkylsulfanylthiophenes to
lead to the formation of oligomers,41 with 1-lithiobutadienes and
1,4-dilithiobutadienes to mediate their dimerization.42
The iron chloride-triphenylphosphine complex effectively cat-
i-PrMgCl, FeCl3
alyzes the electrophilic diamination reaction of electron deficient
alkenes such as Ä…,²-unsaturated carboxylic acids and esters.43
SO2Ph
The reaction uses the readily available N,N-dichloro-p-toluene-
sulfonamide and acetonitrile as nitrogen sources and operates
under very mild and robust conditions (room temperature, cat-
alyst not hygroscopic) without using inert gas. Modest to good
yields are observed and high regio- and stereoselectivity have been
(21)
+
achieved (eq 25).
37%
28%
96% stereoselectivity
CHCl2
96% stereoselectivity
N (25)
TsNCl2, MeCN
COOMe
NTs
Ph
FeCl3-PPh3
Ph COOMe
The reaction of functionalized primary alkyl bromides with
diethylzinc in DMPU in the presence of a catalytic mixed metal
63% yield
system of iron chloride and CuCl provides the corresponding
>95% stereoselectivity
functionalized alkylzinc bromides in high yields (eq 22).38 Sub- (anti/syn)
sequent reaction with a range of electrophiles under copper or
palladium catalysis provides various polyfunctional molecules in
Anhydrous iron chloride oxidizes potassium thiocyanate to
good yields.
the corresponding radical and promotes further addition to
nucleophilic olefins to produce dithiocyanate derivatives in high
FeCl3 (5 mol %)
yield (eq 26).44 In addition to offering the benefits of iron chloride
Oct-Br + Et2Zn Oct-ZnBr
(22)
CuCl2 (3 mol %)
(cheap, readily available, environmentally friendly) the oper-
77% yield
DMPU
ationally simple method is practical and displays remarkable
chemoselectivity. The narrow scope of the method to the more
reactive styrene derivatives, however, reduces its applications.
Organomanganese chlorides react with alkenyl iodides, bro-
mides, or chlorides in the presence of iron salts.39 Various iron(III)
salts can be used as catalysts, provided they are soluble in the
SCN
SCN
reaction mixture. When 2-methallyl bromide is reacted with octyl-
FeCl3
+ KSCN
manganese chloride, which can be prepared by transmetallation
CH3CN
(26)
of the corresponding Grignard reagent with 3 mol % iron chloride,
rt
the resulting product is formed in 67% isolated yield (eq 23). The 78%
reaction takes place under very mild conditions (THF/NMP, rt,
1 h) to afford the corresponding olefin in excellent yields with high
A combination of iron chloride and periodic acid in acetonitrile
stereo- and chemoselectivity. This procedure is an alternative to
catalyzes the selective oxidation of sulfides to sulfoxides (eq 27).45
the more common Pd or Ni-cross-coupling-mediated reactions.
The presence of iron chloride greatly enhances the rate of the
oxidation and leads to the mono-oxidation product in high yield
for a wide range of sulfides.
FeCl3 (3 mol %)
Br Oct (23)
+ Oct-MnCl
THF/NMP
H5IO6/FeCl3
Ph S Ph S
(27)
67%
CH3CN
O
rt
97%
Iron chloride catalyzes olefin carbometallation as exempli-
fied by the addition of Grignard or organozinc reagents to the
oxabicyclo olefin (eq 24).40 Extension to the catalytic version Recently, iron chloride has been increasingly utilized in a wide
with a ternary catalytic system consisting of iron salt, a soft range of organic reactions such as the oxidation of benzoin,46
chiral diphosphine, and a hard diamine has led to good yields the oxidation of readily accessible 1,4-dihydropyridines to the
and enantiomeric excesses. corresponding pyridines under mild conditions,47 the oxidation of
Avoid Skin Contact with All Reagents
4 IRON(III) CHLORIDE
NH2
N3
2-aryl-1,2,3,4-tetrahydroquinolones to 2-aryl-4-methoxyquino-
H2N-N(CH3)2
line (eq 28).48 (31)
FeCl3·6H2O
O2N
O2N
MeOH
rt
OMe
O
81%
FeCl3·6 H2O
(28)
S
S
MeOH
N
N
Reduction of nitroaromatic compounds to the correspond-
H
ing anilines occurs with high chemoselectivity upon treatment
82%
with iron chloride hexahydrate/indium in aqueous methanol at rt
(eq 32).57
Methyl indole-3-acetate can be oxidized with iron chloride in
the presence of diethylamine to give Ä…-(diethylamino)-indole-3-
NH2
NO2
acetate in high yield (eq 29).49
In/FeCl3·6H2O
(32)
H2O/MeOH
HOOC
HOOC
Et2N
sonication
rt
COOMe
COOMe
84%
FeCl3
(29)
Et2NH
N
N
Et2O
H
H
Dehydrogenation of Ä…-haloketones to their corresponding
90%
ketones is accomplished with iron chloride or other metal halides
in THF with or without sulfur salts (eq 33).58
New-oxygen activating systems utilizing iron chloride have
been reported. Dehydrogenation of 2-hydroxymethyl phenols to
O O
the corresponding salicylaldehydes can be catalyzed by a transi-
Cl
tion metal such as Fe(0) or Cu(0), FeCl3 in catalytic amount, and
Na2SO3, FeCl3
(33)
oxygen to give the oxidized product in 80% yield.50
H2O/THF
Barium ruthenate in acetic acid-dichloromethane oxidizes alka-
reflux
nes at room temperature with appreciably increased rates in the
78%
presence of iron chloride.51
Cyclohexane and adamantane are oxidized, although with mod-
est selectivities, in the presence of catalytic amount of iron chlo-
Iron chloride has been used in the synthesis of diarylmethanes as
ride in acetonitrile with oxygen to the corresponding alcohols and
a more practical alternative than late transition metal catalysts.59
ketones under irradiation with visible light.52
It displays the highest performance among other Brłnsted (HCl,
Hydrazones are prepared from hydrazines, iron chloride hex-
HOAc, PTSA, etc.) and Lewis acids (Cu, Co, Zn, Mn, etc.).
ahydrate in refluxing acetonitrile and the corresponding azides
Even hydrated iron(III) salts can be advantageously used under
(eq 30).53 The method is applicable to most primary and sec-
ć%
mild conditions (50 C). Reaction of 2-bromoanisole with
ondary azides and is tolerant of a wide range of functional groups.
1-phenylethyl acetate in the presence of a catalytic amount of
The process furnishes the hydrazones in high yields and without
iron chloride gives the corresponding diarylmethane product in
the need for further purification.
high yield and regioselectivity (eq 34). Interestingly, while the
range of reactivity of arene systems is wide, the scope of the ben-
N(CH3)2
zylation reagent also proved vast: benzyl alcohol, benzyl acetate,
N
N3
benzyl methyl carbonate, 1-phenylethanol. There is basically no
difference between the reaction of benzyl alcohols and benzyl
H2N-N(CH3)2
(30)
acetate, thus making it a state-of-the-art green route to diaryl-
FeCl3Å"6H2O
methanes when benzyl alcohols are used, since water is the only
CH3CN
87% side-product. In all cases, the products are obtained in good yields.
reflux
The regioselectivity is more substrate dependant.
ć%
Higher temperatures (80 C) lead to completion in about 1 h
In combination with Zn metal, iron chloride can chemos- with the same yield while other metals give rise to elimination
electively reduce alkyl, aryl, aroyl, arylsulfonyl azides to the products followed by oligomerization. A wide range of aromatic
corresponding amines or amides in high yields upon treatment and heteroaromatic systems have been used efficiently in this gen-
of the corresponding azides.54 An alternative method uses N,N- eral method for the arylation of benzyl carboxylates and ben-
dimethyl hydrazine in the presence of a catalytic amount of iron zyl alcohols. Typical reactions proceed under mild conditions
ć%
chloride hexahydrate in methanol to reduce azides in high yields (50 80 C, without strong acid or base) and without exclusion
to the corresponding amines (eq 31).55,56 The method is tolerant of air or moisture. It is tolerant of a wide range of functional
of a wide range of functional groups. groups.
A list of General Abbreviations appears on the front Endpapers
IRON(III) CHLORIDE 5
gem-diacetate but also its rearrangement to vinyl acetate. There-
Br
fore, it is necessary to quench the reaction before a significant
AcO
FeCl3 (10 mol %)
+ amount of the desired product undergoes rearrangement in order
CH2Cl2
MeO
to secure high isomeric purity. Among the various Lewis acids
50 °C
20 h
tried, iron chloride gives the best results with a wide range of
anhydrides (acetic, propionic, butyric) and enals.
Br
(34) OAc
Ac2O
TBDPSO CHO (38)
TBDPSO
MeO
FeCl3
OAc
CH3CN
97% yield
regioselectivity >99:1
Iron chloride promotes the condensation of hydroxyimino-
ketones with aminonitriles to afford pyrazines after reduction of
An efficient synthesis of 3,4-dihydropyrimidinones from the
the N-oxide intermediate (eq 39).66 The protocol provides a prac-
aldehyde, ²-keto ester, and urea in ethanol is accomplished with
tical synthesis of 3- and 3,5-substituted 2-aminopyrazines in mod-
iron chloride hexahydrate as catalyst (eq 35).60,61 The one-pot
erate to good yields. The hydrate form of iron chloride displays
reaction in refluxing ethanol has the advantage over the classical
similar efficiency.
Biginelli reaction of good to excellent yields for aryl and alkyl
aldehydes and short reaction times.
Ph O CN
FeCl3
O O O
+
FeCl3 · 6H2O
NH2 MeOH-H2O (24:1)
CHO
+
+ NOH
Ph
OEt H2N NH2 EtOH
reflux
5 h
Ph N Ph N
Ph
H2 (0.5 MPa)
(39)
EtOOC
10% Pd/C
NH
(35)
N N
NH2 NH2
O
O
N
H
85%
Hydrated iron chloride is used as both the Lewis acid and
Diastereoselective aldol reactions of various aldehydes with sil-
the hydrating agent in a process analogous to the Ritter reaction
icon enolates in water have been successfully carried out using iron
(eq 36).62 A variety of nitriles can be reacted for with benzyl
chloride and a surfactant (eq 40).67 Iron chloride is here compati-
chloride to give high yields of the N-benzylamide.
ble with water and no epimerization is observed. Enolates derived
from alkyl, thioesters, and benzoyl are used in modest to good
yields in the process.
Cl FeCl3 · 6H2O
NHCOPh
(36)
Ph CN
OSiMe3 FeCl3 (10 mol %)
CHO
92%
+
surfactant (10 mol %)
Ph
MeO H2O
Iron chloride is used in the solvent-free reaction of oximes
0 °C
to yield the Beckmann rearrangement product in good yields
(eq 37).63 Good selectivities are observed for unsymmetrical
OH
O
oximes. The reaction is inhibited in the presence of solvent.
(40)
Ph
H
MeO
O
N
NOH
FeCl3
(37)
86% yield
neat
91/9 syn/anti
80 90 °C
82%
Iron chloride-catalyzed (5 mol %) allylation reactions of a
Gem-dicarboxylates can be generated readily from the corres- variety of aldehydes with allyltrimethylsilane proceeds efficiently
ponding aldehydes and acetic anhydride in the presence of a and smoothly at room temperature to afford the corresponding
catalytic amount of iron chloride (eq 38).64,65 The reaction is com- homoallylic alcohols in high to excellent yields (eq 41).68 The
ć%
plete in 1 2 h at 0 C providing the trans-product as the major method is particularly suitable for the allylation of sterically hin-
regioisomer. The Lewis acid not only catalyzes formation of the dered aliphatic aldehydes.
Avoid Skin Contact with All Reagents
6 IRON(III) CHLORIDE
OH O
SiMe3
Ph CHO
Ph
FeCl3
CHO
(41) pTol-SO2NH2 + OMe
Ph +
FeCl3 (5 mol %)
amine
Ph
Ph
i-PrOH
CH3NO2
(1:1:1.1)
4 Å MS
92%
O O
S
Tol
NH
O
The allenoate-Claisen rearrangement is promoted by iron chlo-
Ph
ride with high levels of efficiency and diastereocontrol (eq 42).69 OMe (44)
The method is general with respect to the tertiary amine moi-
ety without loss of yield or diastereocontrol and tolerates a wide
65%
range of allenes. The stereoinduction is dictated by the geome-
try of the olefin as predicted for [3,3] sigmatropic rearrangements
Iron chloride promotes 1,5-electrocyclization of nitrilimines
with trans-allyllic amines giving rise to the syn-adduct and the
in good yields such as 6-benzyl-3-(arylmethylidenehydrazino)-
cis-isomer leading to the anti-adduct.
as-triazin-5(4H)-ones to s-triazolo[4,3-b]-as-triazin-7(8H)-ones
with remarkable regioselectivity (eq 45).72
Me
FeCl3
C + Me N
O O
COOBn CH2Cl2
rt
Ph N Ph N
FeCl3
N N
(45)
N NHN=CHPh N
N
EtOH
N
Ph
Me N
(42)
70%
Me COOBn
Iron chloride favors the formation of nitrilium chloroferrate
salts from the corresponding nitrile and tert-butyl chloride, which
83% yield
syn:anti >98:2
upon reaction with an organic base such as triethylamine results
in the formation of N-tert-butylketene (eq 46).73
Anhydrous iron chloride promotes the rearrangement of aryl
PhCH2CN + Cl-t-Bu + FeCl3
arenesulfinates to the corresponding arenesulfinyl phenols via a
thia-Fries reaction in high to excellent yields (eq 43).70 The con-
1. NEt3
PhCH2CHN-t-BuFeCl4 PhC=C=N-t-Bu (46)
ditions are milder than those utilized with aluminum trichloride,
2. NaOH, H2O
thus allowing a wider substrate scope.
An efficient, catalytic, and mild method for the conversion of
O
epoxides to their corresponding ²-alkoxy alcohols consists in their
S
opening with primary, secondary, and tertiary alcohols in the pres-
O
OH
O
ence of a catalytic amount of iron chloride. High yields and stereo-
S
FeCl3
and regioselectivity are observed.74
(43)
Preparation of 1,3-diphenyladamantane from 7-methylene-
CH2Cl2
rt
bicyclo[3.3.1]nonan-3-one and benzene in the presence of iron
OMe
OMe
chloride has been achieved (eq 47).75 Other Lewis acids such as
100% zinc iodide or BF3 etherate have allowed for the incorporation of
various nucleophiles (cyanide, azide, isothiocyanate, enols).
Iron chloride in the presence of 2-hydroxyquinuclidine and
Ph
O
molecular sieves catalyzes the formation of Ä…-methylene-²-amino
FeCl3 (47)
acid derivatives via an aza-Baylis-Hillman reaction in a one-
Ph
pot three-component reaction between an arylaldehyde, a sul- benzene
0 °C to rt
fonamide, and an Ä…,²-unsaturated carbonyl compound (eq 44).71
92%
Slightly better results are obtained with Ti(OiPr)4, Sc(OTf)3, and
Yb(OTf)3. The protocol allows for a wide range of electron-rich
and poor arylaldehydes and Michael acceptors. Minor amounts Iron chloride as a Lewis acid has been used as a promoter
of the Baylis Hillman side-products are formed under these of cationic polyene cyclization,76 intramolecular cycloaddition,77
conditions. intermolecular ene reactions,78 pericyclic reactions,79 and radical
A list of General Abbreviations appears on the front Endpapers
IRON(III) CHLORIDE 7
cyclization of variously substituted N-chloropentenylamines into 12. Neumann, S. M.; Kochi, J. K., J. Org. Chem. 1975, 40, 599.
pyrrolidines.80 13. Cardinale, G.; Laan, J. A. M.; Russell, S. W.; Ward, J. P., Recl. Trav.
Chim. Pays-Bas 1982, 101, 199.
In the field of protecting group chemistry, iron chloride has
14. Ito, Y.; Fujii, S.; Saegusa, T., J. Org. Chem. 1976, 41, 2073.
been used as an efficient reagent for the conversion of alcohols
into diphenylmethyl ether (DPM) and to convert ketals and acid- 15. Ito, S.; Matsumoto, M., J. Org. Chem. 1983, 48, 1133.
sensitive ethers into DPM ethers (eq 48),81 to promote detrity- 16. Kohda, A.; Nagayoshi, K.; Maemoto, K.; Sato, T., J. Org. Chem. 1983,
48, 425.
lation of a variety of mono- and disaccharides without affect-
17. Ichikawa, S.; Tomita, I.; Hosaka, A.; Sato, T., Bull. Chem. Soc. Jpn.
ing benzyl, isopropylidene, isopropylthio, allyl, acetyl, benzoyl
1988, 61, 513.
O-protecting groups,82 to deprotect acetals under mild condi-
18. Denmark, S. E.; Habermas, K. L.; Hite, G. A.; Jones, T. K., Tetrahedron
tions at room temperature in high yields (eq 49),83,84 to de-
1986, 42, 2821.
protect dithioacetals to the corresponding ketones by ferric
19. Denmark, S. E.; Klix, R. C., Tetrahedron 1988, 44, 4043.
chloride/potassium iodide in refluxing methanol in high yields
20. Denmark, S. E.; Wallace, M. A.; Walker, C. B., Jr., J. Org. Chem. 1990,
(eq 50).85 The latter method is applicable to a wide range of
55, 5543.
substrates and offers the advantage of using nontoxic reagents.
21. Tietze, L. F.; Beifuss, U., Synthesis 1988, 359.
22. Snider, B. B.; Roush, D. M., J. Org. Chem. 1979, 44, 4229.
23. Matsuda, T.; Tanino, K.; Kuwajima, I., Tetrahedron Lett. 1989, 30, 4267.
24. Cabral, J.; Laszlo, P.; Mahe, L., Tetrahedron Lett. 1989, 30, 3969.
25. Park, M. H.; Takeda, R.; Nakanishi, K., Tetrahedron Lett. 1987, 28, 3823.
Ph2CHOH
26. Dalla Cort, A., Synth. Commun. 1990, 20, 757.
(48)
ODPM
OH
FeCl3
27. Gross, R. S.; Watt, D. S., Synth. Commun. 1987, 17, 1749.
CH2Cl2
28. Patney, H. K., Synlett 1992, 567.
88%
29. Dasgupta, F.; Garegg, P. J., Acta Chem. Scand. 1989, 43, 471 and
references therein.
30. Ikemoto, N.; Kim, O. K.;, L.-C.; Satyanarayana, V.; Chang, M.;
Nakanishi, K., Tetrahedron Lett. 1992, 33, 4295.
FeCl3·6H2O
O COOEt
COOEt
31. Fuks, R., Tetrahedron 1973, 29, 2147.
OHC
CH2Cl2
32. Kagan, J.; Firth, B. E.; Shih, N. Y.; Boyajian, C. G., J. Org. Chem. 1977,
(49)
O
reflux
42, 343.
33. Effenberger, F.; Steegmuller, D., Ber. Dtsch. Chem. Ges./Chem. Ber.
1988, 121, 117 (Chem. Abstr. 1988, 108, 75 799z).
O
S S
34. Arase, A.; Masuda, Y.; Suzuki, A., Bull. Chem. Soc. Jpn. 1974, 47, 2511.
FeCl3/KI (1:1)
35. Miller, J. A.; Nunn, M. J., J. Chem. Soc., Perkin Trans. 1 1976, 416.
(50)
MeOH
36. Sigma-Aldrich Library of Chemical Safety Data, 2nd ed.; Lenga, R. E.,
reflux
Ed.; Sigma-Aldrich: Milwaukee, WI, 1988; p 1680A.
88%
37. Alvarez, E.; Cuvigny, T.; Hervé du Penhoat, C.; Julia, M., Tetrahedron
1988, 44, 111.
Iron chloride in dichloromethane readily anomerizes ²-glyco- 38. Klement, I.; Knochel, P.; Chau, K.; Cahiez, G., Tetrahedron Lett. 1994,
35, 1177.
pyranosides to their corresponding Ä…-anomers in good yields and
39. Cahiez, G.; Marquais, S., Tetrahedron Lett. 1996, 37, 1773.
selectivities at room temperature.86
40. Nakamura, M.; Hirai, A.; Nakamura, E., J. Am. Chem. Soc. 2000, 122,
978.
Related Reagents. Iron(III) Chloride Acetic Anhydride;
41. Barbarella, G.; Zambianchi, M.; Di Toro, R.; Colonna, M., Jr.; Iarossi,
Iron(III) Chloride Alumina; Iron(III) Chloride Dimethylform-
D.; Goldoni, F.; Bongini, A., J. Org. Chem. 1996, 61, 8285.
amide; iron(III) Chloride Silica gel; Iron(III) Chloride Sodium
42. Li, G.; Fang, H.; Xi, Z., Tetrahedron Lett. 2003, 44, 8705.
Hydride.
43. Wei, H.-X.; Kim, S. H.; Li, G., J. Org. Chem. 2002, 67, 4777.
44. Yadav, J. S.; Reddy, B. V. S.; Gupta, M. K., Synthesis 2004, 1983.
45. Kim, S. S.; Nehru, K.; Kim, S. S.; Kim, D. W.; Jung, H. C., Synthesis
1. Fieser & Fieser 1967, 1, 390.
2002, 2484.
2. Franck, B.; Lubs, H. J., Angew. Chem., Int. Ed. Engl. 1968, 7, 223.
46. Shanxi, Y., Chem. Abstr. 1993, 118, 254484.
3. Kametani, T.; Noguchi, I.; Nyu, K.; Takano, S., Tetrahedron Lett. 1970,
47. Lu, J.; Bai, Y.; Wang, Z.; Yang, B.; Li, W., Synth. Commun. 2001, 31,
723.
2625.
4. Cherest, M.; Lusinchi, X., Tetrahedron Lett. 1989, 30, 715.
48. Hemanth Kumar, K.; Muralidharan, D.; Perumal, P. T., Tetrahedron Lett.
5. Schirch, P. F. T.; Boekelheide, V., J. Am. Chem. Soc. 1979, 101, 3125.
2004, 45, 7903.
6. Broka, C. A., Tetrahedron Lett. 1991, 32, 859.
49. Bergman, J.; Bergman, S.; Lindström, J.-O., Tetrahedron Lett. 1989, 30,
7. Frazier, R. H.; Jr., Harlow, R. L., J. Org. Chem. 1980, 45, 5408.
5337.
8. Paquette, M.-A.; Paquette, L. A., Tetrahedron Lett. 1988, 29, 269.
50. Sparfel, D.; Baranne-Lafont, J.; Cuong, N. K.; Capdevielle, P.; Maumy,
9. Buchi, G.; Freidinger, R. M., Tetrahedron Lett. 1985, 26, 5923. M., Tetrahedron 1990, 46, 793.
10. Tamura, M.; Kochi, J., Synthesis 1971, 303. 51. Lau, T.-C.; Mak, C.-K., J. Chem. Soc., Chem. Commun. 1993, 766.
11. Pasto, D. J.; Hennion, G. F.; Shults, R. H.; Waterhouse, A.; S.-K., J. Org. 52. Takaki, K.; Yamamoto, J.; Matsushita, Y.; Morii, H.; Shishido, T.;
Chem. 1976, 41, 3496. Takehira, K., Bull. Chem. Soc. Jpn. 2003, 76, 393.
Avoid Skin Contact with All Reagents
8 IRON(III) CHLORIDE
53. Barrett, I. C.; Langille, J. D.; Kerr, M. A., J. Org. Chem. 2000, 65, 6268. 71. Balan, D.; Adolfsson, H., J. Org. Chem. 2002, 67, 2329.
54. Kamal, A.; Narayan Reddy, B. S., Chem. Lett. 1998, 593. 72. Shawali, A. S.; Gomha, S., Tetrahedron 2002, 58, 8559.
55. Pathak, D.; Laskar, D. D.; Prajapati, D.; Sandhu, J. S., Chem. Lett. 2000, 73. Fuks, R.; Baudoux, D.; Piccini-Leopardi, C.; Declercq, J.-P.; Van
816. Meersche, M., J. Org. Chem. 1988, 53, 18.
56. Kamal, A.; Venkata Ramana, K.; Babu Ankati, H.; Venkata Ramana, A., 74. Iranpoor, N.; Salehi, P., Synthesis 1994, 1152.
Tetrahedron Lett. 2002, 43, 6861.
75. Olah, G. A.; Krishnamurti, R.; Surya Prakash, G. K., Synthesis 1990,
57. Woo Yoo, B.; Woo Choi, J.; Hwang, S. K.; Kim, D. Y.; Baek, H. S.; Choi, 646.
K. I.; Kim, J. H., Synth. Commun. 2003, 33, 2985.
76. Sen, S. E.; Roach, S. L.; Smith, S. M.; Zhang, Y. Z., Tetrahedron Lett.
58. Ono, A.; Maruyama, T.; Kamimura, J., Synthesis 1987, 1093. 1998, 39, 3969.
59. Iovel, I.; Mertins, K.; Kischel, J.; Zapf, A.; Beller, M., Angew. Chem., 77. Rigby, J. H.; Fleming, M., Tetrahedron Lett. 2002, 43, 8643.
Int. Ed. 2005, 44, 3913.
78. Agouridas, K.; Girodeau, J. M.; Pineau, R., Tetrahedron Lett. 1985, 26,
60. Lu, J.; Ma, H., Synlett 2000, 63. 3115.
61. Lu, J.; Bai, Y., Synthesis 2002, 466. 79. Thomas, N. F.; Lee, K. C.; Paraidathathu, T.; Weber, J. F. F.; Awang, K.;
Rondeau, D.; Richomme, P., Tetrahedron 2002, 58, 7201.
62. Karabulut, H. R. F.; Kacan, M., Synth. Commun. 2002, 32, 2345.
80. Sjöholm, Å.; Hemmerling, M.; Pradeille, N.; Somfai, P., J. Chem. Soc.,
63. Khodaei, M. M.; Meybodi, F. A.; Rezai, N.; Salehi, P., Synth. Commun.
Perkin Trans. 1 2001, 8, 891.
2001, 31, 2047.
81. Sharma, G. V. M.; Rajendra Prasad, T.; Mahalingam, A. K., Tetrahedron
64. Trost, B. M.; Lee, C. B.; Weiss, J. M., J. Am. Chem. Soc. 1995, 117,
Lett. 2001, 42, 759.
7247.
82. Ding, X.; Wang, W.; Kong, F., Carbohydr. Res. 1997, 303, 445.
65. Agouridas, K.; Girodeau, J. M.; Pineau, R., Tetrahedron Lett. 1985, 26,
3115. 83. Sen, S. E.; Roach, S. L.; Boggs, J. K.; Ewing, G. J.; Magrath, J., J. Org.
Chem. 1997, 62, 6684.
66. Itoh, T.; Maeda, K.; Wada, T.; Tomimoto, K.; Mase, T., Tetrahedron Lett.
2002, 43, 9287. 84. Kim, K. S.; Song, Y. H.; Lee, B. H.; Hahn, C. S., J. Org. Chem. 1986,
51, 404.
67. Aoyama, N.; Manabe, K.; Kobayashi, S., Chem. Lett. 2004, 312.
85. Chavan, S. P.; Soni, P. B.; Kale, R. R.; Pasupathy, K., Synth. Commun.
68. Watahaki, T.; Oriyama, T., Tetrahedron Lett. 2002, 43, 8959.
2003, 33, 879.
69. Lambert, T. H.; MacMillan, D. W. C., J. Am. Chem. Soc. 2002, 124,
86. Ikemoto, N.; Kim, O. K.; Lo, L.-C.; Satyanarayana, V.; Chang, M.;
13646.
Nakanishi, K., Tetrahedron Lett. 1992, 33, 4295.
70. Moghaddam, F. M.; Dekamin, M. G.; Ghaffarzadeh, M., Tetrahedron
Lett. 2001, 42, 8119.
A list of General Abbreviations appears on the front Endpapers