IRON(III) CHLORIDE

1

Iron(III) Chloride

1

FeCl

3

[7705-08-0]

Cl

3

Fe

(MW 162.20)

InChI = 1/3ClH.Fe/h3*1H;/q;;;+3/p-3/f3Cl.Fe/h3*1h;/q3*-1;m
InChIKey = RBTARNINKXHZNM-VBTRCSEMCV

(mild oxidant capable of phenolic coupling,

1

dimerizing aryl-

lithiums

6

and ketone enolates;

7,8

mild Lewis acid: catalyzes ene

reactions,

21

Nazarov cyclizations,

18−20

Michael additions,

24

and

acetonations

29

)

Alternate Name:

ferric chloride.

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;

v sol alcohol, MeOH, ether, 63 g mL

−1

in acetone (18

◦

C).

Form Supplied in:

black crystalline powder; widely available.

Preparative Methods:

anhydrous FeCl

3

available commercially

is adequate for most purposes. However, the anhydrous mate-
rial can be obtained from the hydrate by drying with thionyl
chloride

7

or azeotropic distillation with benzene.

12

Handling, Storage, and Precautions:

is hygroscopic and corro-

sive; inhalation or ingestion may be fatal. It causes eye and skin
irritation. It should be stored and handled under an inert dry
atmosphere.

36

Use in a fume hood.

Original Commentary

Andrew D. White
Parke-Davis Pharmaceutical Research, Ann Arbor, MI, USA

Oxidative Properties.

1

FeCl

3

oxidizes a wide array of func-

tionalities, such as certain phenols to quinones (eq 1), dithiols to
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

and N-acetyloxyamides can be cyclized to indoles (eq 4)

3

and

oxindoles (eq 5),

4

respectively. Dimerization of aryllithium or

Grignard reagents yields intermediates for cyclophane

5

and pery-

lenequinone

6

synthesis (eq 6). Inter-

7

and intramolecular

8

ketone

enolates can be converted to 1,4-diketones (eq 7), and lithium salts
of allylic sulfones afford 1,6-disulfones.

9

NH

2

Cl

OH

O

O

OH

O

O

O

O

FeCl

3

, 30 °C

94%

FeCl

3

, 70 °C

97%

(1)

(2)

HS

SH

CO

2

H

S

S

CO

2

H

4

4

FeCl

3

N
H

HO

MeO

OMe

OH

N

HO

MeO

OMe

O

O

CF

3

1. (CF

3

CO)

2

O

(3)

2. FeCl

3

(4)

HO

MeO

NH

2

N
H

HO

MeO

FeCl

3

(5)

FeCl

3

, AcOH

NHOAc

N
H

O

O

CH

2

Cl

2

75%

OTBDPS

MeO

Li

MOMO

OBn

OMe

MOMO

OBn

OMe

MeO

MeO

MOMO

OBn

OMe

OTBDPS

OTBDPS

FeCl

3

(6)

63%

(7)

1. 2 equiv LDA

O

O

O

O

2. FeCl

3

Stereoselective cross-coupling of alkenyl halides with Grignard

reagents is catalyzed by FeCl

3

(45–83%) (eqs 8 and 9).

10

Propar-

gyl halides also react to afford allenes.

11

A study of Fe

III

cata-

lysts revealed that Tris(dibenzoylmethide)iron(III) was the most
useful.

12

(8)

Br

MeMgBr

FeCl

3

(9)

Br

MeMgBr

FeCl

3

Alkylcyclopentanones can be dehydrogenated to cyclopen-

tenones, but Copper(I) Chloride is a better catalyst.

13

Trimethyl-

silyloxybicyclo[n1.0]alkanes

can

be

oxidatively

cleaved,

providing a three-step method of ring expansion (eq 10).

14

Cycloalkanones are cleaved with FeCl

3

/MeOH under O

2

to

ω

-oxo esters; this reaction works best with flanking methyl

groups (eq 11).

15

Photooxidation of alkenes with FeCl

3

can

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

induces a selective C(1)–C(2) bond cleavage, in contrast to Tita-
nium(IV) Chloride

(C(5)–C(6) cleavage) (eq 12).

17

FeCl

3

/EtOH

can also be used to disengage tricarbonyliron complex ligands.

(10)

OTMS

O

1. FeCl

3

, DMF

2. NaOAc

84%

(11)

O

CO

2

Me

O

FeCl

3

, O

2

MeOH

93%

O

O

OH

OH

OH

OH

OH

OHCO

OAc

AcO

OAc (12)

1. hν, FeCl

3

2. Ac

2

O

Lewis Acid Mediated Reactions.

Silicon-directed Nazarov

cyclizations occur readily in dichloromethane catalyzed by FeCl

3

,

utilizing the cation-stabilizing effect of silicon.

18

Cyclohexenyl

systems afford only cis-fused ring products. The reaction has
been elaborated to the preparation of linear tricycles with
β

-silyldivinyl ketones at low temperature (eq 13).

19

Optically

active β

′

-silyl divinyl ketones have been used to demonstrate that

cyclization occurs with essentially complete control by silicon
in the anti S

′

E

sense.

20

FeCl

3

is the best Lewis acid catalyst for

the intramolecular ene reaction of the Knoevenagel adduct from
citronellal and dimethyl malonate at low temperature (eq 14).

21

However, the basic alumina supported catalyst can give more
reliable results. The ene reaction of an unsaturated ester of an
allylic alcohol yields a chlorolactone cleanly at 25

◦

C.

22

This

reaction produces only one of four possible diastereomers, with
clean trans addition to the double bond occurring (eq 15).
1-Silyloxycycloalkanecarbaldehydes undergo ring expansion to
2-silyloxycycloalkanones (82–89%) (eq 16). FeCl

3

catalysis pro-

vides the best selectivity derived from rearrangement of the more
substituted α-carbon atom.

23

FeCl

3

-catalyzed addition of primary

and secondary amines to acrylates occurs exclusively 1,4 with no
polymerization (79–97%) (eq 17).

24

O

TMS

O

H

H

H

(13)

FeCl

3

, –50 °C

79%

MeO

2

C

CO

2

Me

MeO

2

C

CO

2

Me

(14)

FeCl

3

, CH

2

Cl

2

94%

CO

2

Me

O

O

CO

2

Me

CO

2

Me

O

O

CO

2

Me

Cl

H

H

(15)

FeCl

3

, CH

2

Cl

2

85%

(16)

FeCl

3

, –23 °C

OTIPS

CHO

OTIPS

82%

(17)

FeCl

3

CO

2

Et

Et

2

N

CO

2

Et

+

Et

2

NH

96%

In the field of protecting group chemistry FeCl

3

will cleave

benzyl

25

and silyl ethers,

26

convert MEM ethers to carboxylic

esters,

27

and when dispersed on 3Å molecular sieves catalyzes

the formation of MOM ethers.

28

In the area of carbohydrate

chemistry, FeCl

3

is proving a versatile reagent for acetylation,

acetonation, acetolysis, transesterification, O-glycosidation of β-
per-O-acetates, formation of oxazolines, direct conversion of
1,3,4,6-tetra-O-acetyl-2-deoxy-2-acylamido-β-

D

-glucopyranoses

into their O-glycosides, preparation of 1-thioalkyl(aryl)-β-

D

-

hexopyranosides from the peracetylated hexopyranoses having a
1,2-trans configuration,

29

and as an anomerization catalyst for

the preparation of alkyl-α-glycopyranosides (eq 18).

30

O

OMe

OBn

BnO

OBn

BnO

O

RO

RO

OR

RO

(18)

1. FeCl

3

, CH

2

Cl

2

OR

R = 4-MeOCinn

2. RCl, AgOTf

90%

Substituted amidines have been prepared from a nitrile

compound, an alkyl halide, an amine, and FeCl

3

in a one-pot

synthesis (40–80%) (eq 19).

31

FeCl

3

in ether converts epoxides

into chlorohydrins. Fused bicyclic epoxides yield trans-chloro-
hydrins (eq 20).

32

Friedel–Crafts acylation of activated (Me,

OMe substituents) aromatics occurs readily with optically active
N

-phthaloyl-α-amino

acid

chlorides

catalyzed

by

FeCl

3

(1–5 mol%).

33

Trialkylboranes react with FeCl

3

in THF/H

2

O to

afford alkyl chlorides in excellent yield.

34

t

-Alkyl and benzylic

chlorides can be converted to the iodides on reaction with Sodium
Iodide

in benzene catalyzed by FeCl

3

.

35

R

1

CN

+

R

2

Cl

+

H
N

N

R

1

NR

2

(19)

FeCl

3

(20)

O

OH

Cl

1. FeCl

3

, Et

2

O

2. H

2

O

78%

First Update

Fabrice Gallou
Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA

A number of applications of iron chloride in cross-coupling

reactions has appeared recently as an alternative to more con-
ventional organometallic catalysis with transition metals such as
palladium and nickel.

A list of General Abbreviations appears on the front Endpapers

IRON(III) CHLORIDE

3

The stereoselective synthesis of 2-isopropyl 1,4-dienes through

the cross-coupling reaction of 2-benzenesulfonyl 1,4-dienes and
isopropylmagnesium chloride can be mediated by iron salts to
lead to the substitution of the sulfonyl group with stereoselectivity
higher than 96%. In addition, no isomerization of the isopropyl
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

SO

2

Ph

i-PrMgCl, FeCl

3

+

37%

96% stereoselectivity

28%

96% stereoselectivity

(21)

The reaction of functionalized primary alkyl bromides with

diethylzinc in DMPU in the presence of a catalytic mixed metal
system of iron chloride and CuCl provides the corresponding
functionalized alkylzinc bromides in high yields (eq 22).

38

Sub-

sequent reaction with a range of electrophiles under copper or
palladium catalysis provides various polyfunctional molecules in
good yields.

Oct-Br + Et

2

Zn

FeCl

3

(5 mol %)

CuCl

2

(3 mol %)

DMPU

Oct-ZnBr

77% yield

(22)

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
reaction mixture. When 2-methallyl bromide is reacted with octyl-
manganese chloride, which can be prepared by transmetallation
of the corresponding Grignard reagent with 3 mol % iron chloride,
the resulting product is formed in 67% isolated yield (eq 23). The
reaction takes place under very mild conditions (THF/NMP, rt,
1 h) to afford the corresponding olefin in excellent yields with high
stereo- and chemoselectivity. This procedure is an alternative to
the more common Pd or Ni-cross-coupling-mediated reactions.

Br

Oct

Oct-MnCl

FeCl

3

(3 mol %)

THF/NMP

+

67%

(23)

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

with a ternary catalytic system consisting of iron salt, a soft
chiral diphosphine, and a hard diamine has led to good yields
and enantiomeric excesses.

O

OMe

OMe

Ph

OH

OMe

OMe

PhMgBr (2 equiv)

FeCl

3

(0.1 equiv)

THF

25

°

C, 16 h

then NH

4

Cl

62%

(24)

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-

alyzes the electrophilic diamination reaction of electron deficient
alkenes such as α,β-unsaturated carboxylic acids and esters.

43

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
achieved (eq 25).

Ph

COOMe

N

NTs

Ph

COOMe

CHCl

2

TsNCl

2

, MeCN

63% yield

>95% stereoselectivity

(anti/syn)

FeCl

3

-PPh

3

(25)

Anhydrous iron chloride oxidizes potassium thiocyanate to

the corresponding radical and promotes further addition to
nucleophilic olefins to produce dithiocyanate derivatives in high
yield (eq 26).

44

In addition to offering the benefits of iron chloride

(cheap, readily available, environmentally friendly) the oper-
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.

SCN

SCN

KSCN

FeCl

3

+

CH

3

CN

rt

78%

(26)

A combination of iron chloride and periodic acid in acetonitrile

catalyzes the selective oxidation of sulfides to sulfoxides (eq 27).

45

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.

Ph

S

Ph

S

O

H

5

IO

6

/FeCl

3

CH

3

CN

rt

97%

(27)

Recently, iron chloride has been increasingly utilized in a wide

range of organic reactions such as the oxidation of benzoin,

46

the oxidation of readily accessible 1,4-dihydropyridines to the
corresponding pyridines under mild conditions,

47

the oxidation of

Avoid Skin Contact with All Reagents

4

IRON(III) CHLORIDE

2-aryl-1,2,3,4-tetrahydroquinolones to 2-aryl-4-methoxyquino-
line (eq 28).

48

N
H

S

O

N

S

OMe

FeCl

3

·6 H

2

O

MeOH

82%

(28)

Methyl indole-3-acetate can be oxidized with iron chloride in

the presence of diethylamine to give α-(diethylamino)-indole-3-
acetate in high yield (eq 29).

49

N
H

COOMe

N
H

COOMe

Et

2

N

FeCl

3

90%

Et

2

NH

Et

2

O

(29)

New-oxygen activating systems utilizing iron chloride have

been reported. Dehydrogenation of 2-hydroxymethyl phenols to
the corresponding salicylaldehydes can be catalyzed by a transi-
tion metal such as Fe(0) or Cu(0), FeCl

3

in catalytic amount, and

oxygen to give the oxidized product in 80% yield.

50

Barium ruthenate in acetic acid-dichloromethane oxidizes alka-

nes at room temperature with appreciably increased rates in the
presence of iron chloride.

51

Cyclohexane and adamantane are oxidized, although with mod-

est selectivities, in the presence of catalytic amount of iron chlo-
ride in acetonitrile with oxygen to the corresponding alcohols and
ketones under irradiation with visible light.

52

Hydrazones are prepared from hydrazines, iron chloride hex-

ahydrate in refluxing acetonitrile and the corresponding azides
(eq 30).

53

The method is applicable to most primary and sec-

ondary azides and is tolerant of a wide range of functional groups.
The process furnishes the hydrazones in high yields and without
the need for further purification.

N

3

H

2

N-N(CH

3

)

2

N

N(CH

3

)

2

FeCl

3

⋅

6H

2

O

CH

3

CN

reflux

87%

(30)

In combination with Zn metal, iron chloride can chemos-

electively reduce alkyl, aryl, aroyl, arylsulfonyl azides to the
corresponding amines or amides in high yields upon treatment
of the corresponding azides.

54

An alternative method uses N,N-

dimethyl hydrazine in the presence of a catalytic amount of iron
chloride hexahydrate in methanol to reduce azides in high yields
to the corresponding amines (eq 31).

55,56

The method is tolerant

of a wide range of functional groups.

N

3

O

2

N

H

2

N-N(CH

3

)

2

NH

2

O

2

N

FeCl

3

·

6H

2

O

MeOH
rt

81%

(31)

Reduction of nitroaromatic compounds to the correspond-

ing anilines occurs with high chemoselectivity upon treatment
with iron chloride hexahydrate/indium in aqueous methanol at rt
(eq 32).

57

NO

2

HOOC

NH

2

HOOC

In/FeCl

3

·6H

2

O

84%

H

2

O/MeOH

sonication

rt

(32)

Dehydrogenation of α-haloketones to their corresponding

ketones is accomplished with iron chloride or other metal halides
in THF with or without sulfur salts (eq 33).

58

O

Cl

O

78%

Na

2

SO

3

, FeCl

3

H

2

O/THF

reflux

(33)

Iron chloride has been used in the synthesis of diarylmethanes as

a more practical alternative than late transition metal catalysts.

59

It displays the highest performance among other Brønsted (HCl,
HOAc, PTSA, etc.) and Lewis acids (Cu, Co, Zn, Mn, etc.).
Even hydrated iron(III) salts can be advantageously used under
mild conditions (50

◦

C). Reaction of 2-bromoanisole with

1-phenylethyl acetate in the presence of a catalytic amount of
iron chloride gives the corresponding diarylmethane product in
high yield and regioselectivity (eq 34). Interestingly, while the
range of reactivity of arene systems is wide, the scope of the ben-
zylation reagent also proved vast: benzyl alcohol, benzyl acetate,
benzyl methyl carbonate, 1-phenylethanol. There is basically no
difference between the reaction of benzyl alcohols and benzyl
acetate, thus making it a state-of-the-art green route to diaryl-
methanes when benzyl alcohols are used, since water is the only
side-product. In all cases, the products are obtained in good yields.
The regioselectivity is more substrate dependant.

Higher temperatures (80

◦

C) lead to completion in about 1 h

with the same yield while other metals give rise to elimination
products followed by oligomerization. A wide range of aromatic
and heteroaromatic systems have been used efficiently in this gen-
eral method for the arylation of benzyl carboxylates and ben-
zyl alcohols. Typical reactions proceed under mild conditions
(50–80

◦

C, without strong acid or base) and without exclusion

of air or moisture. It is tolerant of a wide range of functional
groups.

A list of General Abbreviations appears on the front Endpapers

IRON(III) CHLORIDE

5

Br

MeO

AcO

Br

MeO

+

FeCl

3

(10 mol %)

CH

2

Cl

2

50

°C

20 h

97% yield
regioselectivity >99:1

(34)

An efficient synthesis of 3,4-dihydropyrimidinones from the

aldehyde, β-keto ester, and urea in ethanol is accomplished with
iron chloride hexahydrate as catalyst (eq 35).

60,61

The one-pot

reaction in refluxing ethanol has the advantage over the classical
Biginelli reaction of good to excellent yields for aryl and alkyl
aldehydes and short reaction times.

OEt

O

O

Ph

CHO

H

2

N

NH

2

O

FeCl

3

·

6H

2

O

N
H

NH

EtOOC

Ph

O

+

+

EtOH
reflux

5 h

(35)

Hydrated iron chloride is used as both the Lewis acid and

the hydrating agent in a process analogous to the Ritter reaction
(eq 36).

62

A variety of nitriles can be reacted for with benzyl

chloride to give high yields of the N-benzylamide.

Cl

FeCl

3

·

6H

2

O

Ph–CN

NHCOPh

92%

(36)

Iron chloride is used in the solvent-free reaction of oximes

to yield the Beckmann rearrangement product in good yields
(eq 37).

63

Good selectivities are observed for unsymmetrical

oximes. The reaction is inhibited in the presence of solvent.

NOH

H
N

O

FeCl

3

neat

80–90

°C

82%

(37)

Gem

-dicarboxylates can be generated readily from the corres-

ponding aldehydes and acetic anhydride in the presence of a
catalytic amount of iron chloride (eq 38).

64,65

The reaction is com-

plete in 1–2 h at 0

◦

C providing the trans-product as the major

regioisomer. The Lewis acid not only catalyzes formation of the

gem

-diacetate but also its rearrangement to vinyl acetate. There-

fore, it is necessary to quench the reaction before a significant
amount of the desired product undergoes rearrangement in order
to secure high isomeric purity. Among the various Lewis acids
tried, iron chloride gives the best results with a wide range of
anhydrides (acetic, propionic, butyric) and enals.

CHO

TBDPSO

Ac

2

O

FeCl

3

CH

3

CN

OAc

TBDPSO

OAc

(38)

Iron chloride promotes the condensation of hydroxyimino-

ketones with aminonitriles to afford pyrazines after reduction of
the N-oxide intermediate (eq 39).

66

The protocol provides a prac-

tical synthesis of 3- and 3,5-substituted 2-aminopyrazines in mod-
erate to good yields. The hydrate form of iron chloride displays
similar efficiency.

NOH

O

Ph

CN

NH

2

FeCl

3

N

N

NH

2

Ph

O

N

N

NH

2

Ph

+

MeOH-H

2

O (24:1)

85%

10% Pd/C

H

2

(0.5 MPa)

(39)

Diastereoselective aldol reactions of various aldehydes with sil-

icon enolates in water have been successfully carried out using iron
chloride and a surfactant (eq 40).

67

Iron chloride is here compati-

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.

CHO

MeO

OSiMe

3

Ph

O

Ph

OH

MeO

FeCl

3

(10 mol %)

+

surfactant (10 mol %)

H

2

O

0

°C

86% yield
91/9 syn/anti

(40)

Iron chloride-catalyzed (5 mol %) allylation reactions of a

variety of aldehydes with allyltrimethylsilane proceeds efficiently
and smoothly at room temperature to afford the corresponding
homoallylic alcohols in high to excellent yields (eq 41).

68

The

method is particularly suitable for the allylation of sterically hin-
dered aliphatic aldehydes.

Avoid Skin Contact with All Reagents

6

IRON(III) CHLORIDE

Ph

CHO

Ph

SiMe

3

Ph

Ph

OH

FeCl

3

(5 mol %)

CH

3

NO

2

92%

(41)

The allenoate-Claisen rearrangement is promoted by iron chlo-

ride with high levels of efficiency and diastereocontrol (eq 42).

69

The method is general with respect to the tertiary amine moi-
ety without loss of yield or diastereocontrol and tolerates a wide
range of allenes. The stereoinduction is dictated by the geome-
try of the olefin as predicted for [3,3] sigmatropic rearrangements
with trans-allyllic amines giving rise to the syn-adduct and the
cis

-isomer leading to the anti-adduct.

Me

C

COOBn

Me

N

FeCl

3

Me

Me

N

COOBn

+

CH

2

Cl

2

rt

83% yield
syn

:anti >98:2

(42)

Anhydrous iron chloride promotes the rearrangement of aryl

arenesulfinates to the corresponding arenesulfinyl phenols via a
thia-Fries reaction in high to excellent yields (eq 43).

70

The con-

ditions are milder than those utilized with aluminum trichloride,
thus allowing a wider substrate scope.

O

S

O

OMe

S

O

OMe

OH

FeCl

3

100%

CH

2

Cl

2

rt

(43)

Iron chloride in the presence of 2-hydroxyquinuclidine and

molecular sieves catalyzes the formation of α-methylene-β-amino
acid derivatives via an aza-Baylis-Hillman reaction in a one-
pot three-component reaction between an arylaldehyde, a sul-
fonamide, and an α,β-unsaturated carbonyl compound (eq 44).

71

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
of the Baylis–Hillman side-products are formed under these
conditions.

Ph

CHO

O

OMe

O

OMe

Ph

NH

S

Tol

O

O

FeCl

3

+ pTol-SO

2

NH

2

+

(1:1:1.1)

amine

i

-PrOH

4 Å MS

65%

(44)

Iron chloride promotes 1,5-electrocyclization of nitrilimines

in good yields such as 6-benzyl-3-(arylmethylidenehydrazino)-
as

-triazin-5(4H)-ones to s-triazolo[4,3-b]-as-triazin-7(8H)-ones

with remarkable regioselectivity (eq 45).

72

N

N

N

O

NHN=CHPh

Ph

N

N

N

O

Ph

N

N

Ph

FeCl

3

EtOH

70%

(45)

Iron chloride favors the formation of nitrilium chloroferrate

salts from the corresponding nitrile and tert-butyl chloride, which
upon reaction with an organic base such as triethylamine results
in the formation of N-tert-butylketene (eq 46).

73

PhCH

2

CHN-t-BuFeCl

4

PhC=C=N-t-Bu

1. NEt

3

PhCH

2

CN + Cl-t-Bu + FeCl

3

2. NaOH, H

2

O

(46)

An efficient, catalytic, and mild method for the conversion of

epoxides to their corresponding β-alkoxy alcohols consists in their
opening with primary, secondary, and tertiary alcohols in the pres-
ence of a catalytic amount of iron chloride. High yields and stereo-
and regioselectivity are observed.

74

Preparation of 1,3-diphenyladamantane from 7-methylene-

bicyclo[3.3.1]nonan-3-one and benzene in the presence of iron
chloride has been achieved (eq 47).

75

Other Lewis acids such as

zinc iodide or BF

3

etherate have allowed for the incorporation of

various nucleophiles (cyanide, azide, isothiocyanate, enols).

Ph

Ph

O

FeCl

3

benzene

0

°

C to rt

92%

(47)

Iron chloride as a Lewis acid has been used as a promoter

of cationic polyene cyclization,

76

intramolecular cycloaddition,

77

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
pyrrolidines.

80

In the field of protecting group chemistry, iron chloride has

been used as an efficient reagent for the conversion of alcohols
into diphenylmethyl ether (DPM) and to convert ketals and acid-
sensitive ethers into DPM ethers (eq 48),

81

to promote detrity-

lation of a variety of mono- and disaccharides without affect-
ing benzyl, isopropylidene, isopropylthio, allyl, acetyl, benzoyl
O

-protecting groups,

82

to deprotect acetals under mild condi-

tions at room temperature in high yields (eq 49),

83,84

to de-

protect dithioacetals to the corresponding ketones by ferric
chloride/potassium iodide in refluxing methanol in high yields
(eq 50).

85

The latter method is applicable to a wide range of

substrates and offers the advantage of using nontoxic reagents.

OH

Ph

2

CHOH

FeCl

3

CH

2

Cl

2

ODPM

88%

(48)

O

COOEt

O

FeCl

3

·6H

2

O

OHC

COOEt

CH

2

Cl

2

reflux

(49)

S

S

O

FeCl

3

/KI (1:1)

MeOH

reflux

88%

(50)

Iron chloride in dichloromethane readily anomerizes β-glyco-

pyranosides to their corresponding α-anomers in good yields and
selectivities at room temperature.

86

Related

Reagents.

Iron(III)

Chloride–Acetic Anhydride;

Iron(III) Chloride–Alumina; Iron(III) Chloride–Dimethylform-
amide; iron(III) Chloride–Silica gel; Iron(III) Chloride–Sodium
Hydride.

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Avoid Skin Contact with All Reagents

8

IRON(III) CHLORIDE

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A list of General Abbreviations appears on the front Endpapers