INDIUM 1

Indium γ-coupling are observed. α,β-Unsaturated carbonyl compounds

give exclusively 1,2-addition products (eq 6).1
In H2C=CHCH2I
O OH
In
Bu Bu (2)
[7440-74-6] In (MW 114.82) DMF, rt
89%
InChI = 1S/In
InChIKey = APFVFJFRJDLVQX-UHFFFAOYSA-N
O HO
H2C=CHCH2I
In
(effective mediator for the allylation of carbonyl compounds) (3)
DMF, rt
Physical Data: mp 156 ◦ C; bp 2080 ◦ C; d 7.300 g cm−3 at 20 ◦ C. 89%
t-Bu t-Bu
Form Supplied in: readily available in high purity (>99.9%) in
the form of bars, foils, wire, granules, shot, and powders of ax:eq = 83:17
various sizes. For synthetic purposes, indium powder of about
60 mesh is the most convenient form. trans-MeCH=CHCH2Br OH
In
Handling, Storage, and Precaution: generally regarded as non- PhCHO Ph (4)
DMF, rt
toxic. Care must be taken with the flammability of fine powders. 94%
Indium is virtually unreactive towards air and water and can thus erthyro:threo = 66:34
be stored indefinitely.
Me2C=CHCH2Br OH
In
Me(CH2)6CHO Me(CH2)6 (5)
Original Commentary DMF, rt
70%

Timothy B. Lowinger H2C=CHCH2I

O In OH
The Ohio State University, Columbus, OH, USA (6)
Ph DMF, rt Ph
92%
Allylation of Carbonyl Compounds.1 Indium is a very
effective mediator for the addition of allyl groups to carbonyl One significant advantage of allylindium sesquihalides over
compounds under very mild reaction conditions. Typically, the alternative organometallic allylating reagents (allylmagnesium
organoindium reagent is prepared in situ by the addition of an halides, allyllithium compounds) is their low basicity. Yields re-
allyl iodide to a suspension of indium powder in a suitable sol- main high even in the presence of an active hydrogen, such as
vent. The preparation of highly activated indium powder (Rieke in the case of salicylaldehyde (eq 7).1 This property has been
indium) via reduction of indium(III) chloride has been reported,2 exploited by Chan and Li, who have reported indium-mediated
but in the vast majority of cases commercial indium powder is allylations of carbonyl compounds carried out in water.8 These
sufficient. Allyl bromides are equally well suited for this reaction, workers report that in contrast to similar reactions with zinc and
but allyl chlorides are not sufficiently reactive, resulting in dimin- tin, where acid catalysts, heat, or sonication are often required,
ished yields. Studies by Butsugan and co-workers1 suggest that the indium-mediated reaction proceeds readily without the need
the active organoindium species is the allylic indium sesquihalide of a promoter.
(eq 1), which is in accord with results of Gynane and Worrall.3
OH
R I R H2C=CHCH2I
3 RI + 2 In In In (1) CHO
In
R I I (7)
R = allyl DMF, rt
OH 98% OH

Studies of the variation of the yields of allylation as a function

of the ratio of indium:allyl iodide:ketone have shown that two- The mildness of the reaction conditions employed for indium-
thirds of the allyl groups are transferred to carbonyl compounds, mediated allylation can also be advantageous when allylating la-
and thus the stoichiometry of the reaction is 2:3:2 (indium:allyl bile carbonyl compounds. For example, attempts to allylate the
halide:ketone).1 In cases where quantitative utilization of the allyl tricarbonyliron butadiene complex (1) with allylmagnesium bro-
halide is important, this can be achieved by substituting indium(I) mide fail completely, yielding only unidentifiable decomposition
iodide for metallic indium.4 products. In contrast, the indium-mediated allylation of (1) (eq 8)
Allylindium sesquihalides react readily with a variety of car- proceeds smoothly to give the corresponding homoallyl alcohols
bonyl compounds, including ketones (eqs 2 and 3),1 aldehydes in 91% yield.9
(eqs 4 and 5),1 acid anhydrides,5 quinones,6 and aldimines.7 H2C=CHCH2Br
Fe(CO)3 Fe(CO)3
In general, the stereoselectivity obtained in these reactions is In OH
low to moderate. For example, indium-mediated allylation of MeO2C CHO THF, rt MeO2C
4-t-butylcyclohexanone (eq 3) gives an 83:17 mixture of axial: (1) 91%
equatorial products. In the case of substituted allyl halides (eqs 4
(8)
and 5), regioselectivity is extremely high as only the products of
2 INDIUM

First Update the method of preparation and the media in which the agent is gen-
erated. Allylic indium species generated from allylic metal (allylic
Teck-Peng Loh Grignard, allylic lithium, allylic stannane, etc.) by transmetalla-
National University of Singapore, Singapore tion with InX3 presumably provides the RInX2 species (eq 13).
The use of dry organic solvent (e.g., DMF, THF, etc.) along with
Introduction. The use of indium in organic synthesis has been indium powder and allylic halides generates indium sesquihalide
increasing rapidly in recent years.10 Especially noteworthy is the species (R3 In2 X3 ) (eq 12). However, it has recently been shown
application of indium-mediated allylation reactions to the synthe- that indium(I) species play a major role when generated in aque-
sis of complex molecules. This further widens the synthetic utility ous media (eq 14).14a However, it is not clear whether one or more
of organoindium reagents. species is involved in the allylation reaction.
O HO Me
Addition of Allylic Indium to Carbonyl Compounds. The I DMF
+ + In (12)
addition of allylic indium to carbonyl compounds has been most Ph Me rt, 1 h Ph
91%
extensively studied because it yields synthetically useful homoal-
lylic alcohols. In recent years, new allylic indium reagents have 2.0 equiv 3.0 equiv 2.0 equiv
been developed. For example, the reaction of trifluoromethylated
allylic bromide provides easy access to a wide variety of trifluo-
romethylated alcohols (eq 9).11 X
In In
O OH X X
In
+ F3C Br (9) X=I
Ph H H2O Ph
rt, 15 h
CF3
82% 1. D-Ribose
InCl3 EtOH:H2O (10:1)
anti/syn (85:15) MgBr InX2
Ether 2. Ac2O, py, DMAP
75%
The reaction of 5-bromo-1,3-pentadiene with indium metal
X=Cl
in the presence of carbonyl compounds results in a 1,4-diene
(eq 10).12 Elimination of the resulting alcohol affords cross-
conjugated triene systems which can be used to react with
appropriate dienophiles to give tandem intermolecular Diels– AcO
Alder adducts. OAc (13)

O OAc
In OAc
+ Br
Naphthyl H DMF OAc
72%
O

In R1 R2
Br In(I)
OH H2O H2O
(10)
Naphthyl OH
R1 (14)
R2
The reactions with a synthetic equivalent of carbonyl com-
pounds have also been explored. Due to the possibility of
carrying out indium-mediated allylation reaction in water, the Stereochemical Studies. The stereochemical aspects of this
indium-mediated allylation reaction of trifluoromethyl acetalde- reaction continue to be studied extensively. Enantioselective ver-
hyde hemiacetal in water has provided easy entry to a wide variety sions of indium-mediated allylations of carbonyl compounds have
of trifluoromethylated carbinols (eq 11).13 also emerged.

OH OH Regioselectivity.
In
+ Br (11)
F3 C OEt H 2O
F 3C
rt, 15 h
α- vs γ-Regioselectivity. Reactions of α- or γ-subsituted allylic
85% halides can result in the formation of either the γ-branched ho-
moallylic alcohols or α-linear homoallylic alcohols. Scheme 1
shows the regioselectivity in indium-mediated allylation. In most
Allylic Indium Reagent. Investigation into the nature of the of the cases studied so far, γ-regioselectivities were observed ex-
active indium species involved in these reactions has been a sub- cept for some special cases where bulky allylic halides (Me3 Si,
ject of great interest. It has been proposed that indium(I)14a (RIn) Me2 PhS, or t-Bu) were used.15
(eq 14), indium(III) (RInX2 ) (eq 13),14b or indium sesquihalides A novel general strategy to obtain the α-linear homoallylic al-
(R3 In2 X3 ) (eq 12)14c can be involved in the reaction depending on cohols has been developed (eqs 15 and 16).16 This strategy makes
 INDIUM 3
R Br
O OH
γ α O Br O
Ph Ph (17)
O In, THF/H2O
87%
R′ H
In/H2O

Most recently, it has been found that the addition of chlorotri-

methylsilane (TMSCl) to the reaction system with certain cyclic
enones results in the reversal of selectivity (eq 18).18
OH OH
γ α γ R
R′ α R′ O
O
R
I TMSCl
γ-attack + + In
α-attack THF
(R = Ph, Me, CO2Me) (R = SiMe3, SiMe2Ph, t-Bu) n 70% n

(18)
Scheme 1

However, in reactions involving 2-cyclopenten-1-one, 2-

methylcyclopenten-1-one, 4,4-dimethylcyclohexen-1-one, and
use of the facile oxonium [3,3] sigmatropic rearrangement of the acyclic α,β-unsaturated enones, 1,2-addition products were ob-
γ-branched homoallylic alcohol to the α-linear homoallylic al- served exclusively. A more general method using TBSOTf, Me2 S,
cohols in the presence of indium complexes generated after the and allylic organoindiums reagents to afford the 1,4-product in
allylation reaction. This reaction can be performed with a wide good yields has been reported.19
range of aldehydes and allylic halides with just 6 equiv of water
added, giving the α-adduct in high selectivities. This method is Diastereofacial Selectivity. The reaction of allylic indium with
also applicable to reactions promoted by tin and zinc. Mechanis- α-hydroxy and β-hydroxy aldehydes leads to products with high
tic studies have also revealed that retrocleavage of the γ-branched chelation control (eqs 19 and 20).20
homoallylic alcohol generates trace amounts of aldehyde which
further facilitate this rearrangement. OH Br
H
cHe In, H2O, 5 h
OH 2-oxonia Cope 85–90%
O In, H2O (6 equiv) rearrangement O

CH2Cl2 R1
R1 H OH OH
R2
cHe + cHe (19)
OH OH OH
(15)
R2 9.8:1
R1

O OH O Br

R1 Br R′ H H In, H2O, 5 h
γ α In
R2 6 equiv H2O
OH OH OH OH
+ (20)
OH OH
α γ R γ α
1
R′ + R′ (16)
8.5:1
R2 R1 R2

α-attack γ-attack
On the other hand, the reaction with non-chelating functional
85%, α:γ (99:1) group of aldehydes containing chiral centers has also been per-
formed. Some of the studies have resulted in very good Cram
selectivity. For example, the addition of a bulky allylic indium to
chiral steroidal aldehyde was found to afford the product up to
1,2- vs 1,4-Addition. The addition of allylic indium to α,β- 99:1 selectivity (eq 21).21 In some cases, the addition of water-
unsaturated aldehydes and ketones resulted in the 1,2-addition stable Lewis acids [e.g., Yb(OTf)3 , La(OTf)3 , etc.] increased the
product (eq 17).17 yields and selectivities of the Cram product.22
4 INDIUM

O OH
R3
In, H2O
H R1 Br
R Br + R′CHO
90% R′
R2 R
In, DMF, 72 h

R R′ anti:syn (ratio)
O cis-COOEt Ph 99:1
OH R3 COOEt 5:95

N
R1 R2

(21) Scheme 3

O
H
OH
51–85% yield
H O In
76:34–99:1 ratio EtO2C R
H CO2Et

Simple Diastereoselectivity. The addition of γ-substituted

allylic indium to carbonyl compounds will lead to the possible OH
N
mixtures of diastereomers. While the reaction with a smaller
R
allylic bromide (such as crotyl bromide) afforded the product H O In
EtO2C CO2Et
in a non-selective manner, the use of a more bulky allylic
bromide (such as cinnamyl bromide, crotonyl allylic bromide, H
trifluoromethyl allylic bromide, etc.) afforded the products ex-
hibiting excellent anti-selectivity (Scheme 2).15a,23 A cyclic or Scheme 4
Zimmerman–Traxler transition state has been proposed to ac-
count for this phenomenon. Interestingly, the Z-allylic bromide
also gives the anti-product. Isomerization of the Z-allylic indium CH3 O CH3 CH3 CH3
to the corresponding E-allylic bromide has been invoked to ac- O CH3
count for this abnormal observation. syn-Selective product can be H 3C N CH3
N H
obtained using an aldehyde containing α-chelating group which H O
N CH3
can bind to the allylic indium reagent (Scheme 3 and 4). H 3C
O
CH3 O

OH OH antillatoxin
O R Br
R′ + R′
R′ H In
R R CH3 CH3 CH3
HO CH3
syn anti
CH3
R=Me; low selectivity
HO CH3
R=Ph, CO2R, CF3, etc.;
excellent anti-selectivity O

Scheme 2

CH3 CH3 CH3

X CH3 CH3
O
While working towards the total synthesis of antillatoxin, both + CH3
the reactivity as well as the simple diastereoselectivity of various Br
H
new allylic bromides were explored (Scheme 5).24
syn-Diastereoselectivity is observed for the indium-mediated X=Br, CO2Me,
coupling of aldehydes regardless of allylic bromide geometry CH2OR, CH2CH2OR
(eq 22).24d An open-chain transition state has been proposed to
account for this unusual selectivity.24d Scheme 5
 INDIUM 5

Enantioselectivity. Enantioselective variants of the indium-

TBDPSO
In, La(OTf)3 mediated allylation of aldehydes have been reported. (−)-
+ R′CHO
THF/H2O, rt, 16 h Cinchonidine and (+)-cinchonine have been found to be good
Br 68–91% chiral promoters for the indium-mediated allylation in organic
solvent, which gave up to 90% ee (eq 24).26 Subsequently, this
E or Z
method has been applied in the synthesis of an advanced interme-
OH
(22)
diate to antillatoxin.24
OTBDPS
R' O Indium/Chiral ligand
Me +
Ph H Br THF:Hexane (3:1)
syn:anti (81:19–99:1)
OH
An unreactive secondary allyl bromide has been found to react * (24)
with aldehydes smoothly in the presence of indium and La(OTf)3 Ph
(eq 23).24a This reaction afforded the α-product in good yield with
moderate syn-selectivities. 99%, 90% ee (R)

Br In, La(OTf)3
OTBDPS + R′CHO
THF/H2O, rt, 12 h
Me 78% H N
HO
OH
(23) Chiral ligand =
R' OTBDPS
Me N

syn:anti (70:30) (–)-Cinchonidine

On the other hand, enantioselective allylation in aqueous media

The reaction of more functionalized allylic bromides with
has been achieved with reasonable success using (S,S)- 2,6-bis-
hexanal under solvent-free conditions provides a straightforward
(4-isopropyl-2-oxazolin-2-yl)pyridine (2) as chiral ligand, afford-
method for the synthesis of the key intermediate of methylenelac-
ing the product up to 92% ee (eq 25). Ce(OTf)4 ·xH2 O is found
tocin and phaseolinic acid (Scheme 6). Although the selectiv-
to increase the yield and enantioselectivity.27 Unfortunately, de-
ity of the reaction was low, both isomers can be converted to
tailed studies also suggested that the chiral ligand slowly decom-
methylenelactocin.25
poses under the reaction conditions, thereby limiting its broad
application.23
Br CO2Me H
In
+ Indium/Chiral ligand
O O
C5H11 neat, 3 days Ce(OTf)4 . xH2O
MeO2C 85%
Ph H + Br EtOH:H2O (1:1)
rt, 30 min

OH
MeO2C CO2Me * (25)
H Ph
H
+ 92% ee (R)
C5H11
O C5H11 MeO2C
HO
O
40% 45% O O
N
Chiral ligand = N N
i-Pr i-Pr
2
CO2H
HO2C H
H C5H11 A Novel Remote Subsituent Effect for Acyclic Stereocontrol.
C5H11 O The allylation of an (R,R)-keto ester affords the product in ex-
O tremely high diastereoselectivity (eq 26). Detailed mechanistic
O O
studies suggested that blocking of the Si face of the carbonyl
(±)-Methylenolactocin (±)-Phaseolinic acid group by the remote phenyl group plays a key role in control-
ling the stereochemistry. This new strategy has been employed
Scheme 6 for the synthesis of a key intermediate of dysiherbaine.28
6 INDIUM

Br
Si indium reagents and the more substituted carbon of the cyclo-
O propene double bond (eq 29).31
F3COC O
N
O R R R
In, THF/H2O
MeO2C 72% Allyl3In2I3 Hex Hex
CO2Me + (29)
Re Hex THF, reflux, 4 h

COCF3
Ph N OH O R = CH2OH, CO2H; 81–95%; 93:7–100:0
O R = CH2OAc, CO2Et; 63–66%; 26:74–0:100
MeO2C
CO2Me

single isomer Allylation of Terminal Alkynes. In addition to the reaction

with carbonyl compounds, the pre-formed allylindium undergoes
NH3+ NH2CH3+ allylindation smoothly at elevated temperatures with terminal
H
–OOC OH
O (26) alkynes bearing a neighboring hydroxyl group (eq 30).32a The
pendant OH facilitates the allylindation process, without which
–OOC
O the coupling becomes sluggish. Whether syn-addition occurs at
H
the γ-carbon of the allylindium exclusively and regioselectiv-
Dysiherbaine ity at the triple bond of the alkynols largely depends on the
structures of both allylindium and alkynols. In most cases, anti-
Markovnikov addition products predominate. By means of this
Indium-mediated Allylation of Non-carbonyl method, three monoterpene alcohols, i.e., yomogi alcohol, achil-
Electrophiles. Indium-mediated allylation has not only lenol, and isomyrcenol, have been conveniently prepared.
been performed with aldehydes and ketones but also with other
electrophiles. In2Br3 DMF
+
OH 91%
Allylation of Imines and Iminium Ions. The addition of 3

allylic indium reagents to chiral imines in DMF provides easy

access to enantiomerically enriched amines. This reaction works OH
+ (30)
with non-enolizable imines and in dry organic solvents (eq 27).29 OH
When imines derived from α-amino esters were reacted with
allyl bromide in the presence of indium, the desired products were 65:35
observed with selectivities ranging from 95:5 to 99:1.
As the solvent is changed to THF, the allylation reaction also
proceeds with unactivated terminal alkynes, affording the 1,4-
Br dienes in good yields (eq 31).32b The method is exceptional with
N CO2Et HN CO2Et (27) its simple procedure, high yields, and excellent Markovnikov re-
In, DMF gioselectivity. THF was found to be the best solvent and the pres-
R H 50–80% R
ence of water proved detrimental. The method has shortcomings
(S,S) dr 95:5–99:1 in its inapplicability to internal alkynes.

The reaction of allylic indium with iminium salts derived from Br +

THF
(31)
R + In
pyridium has been found to be 1,2-regioselective, providing a good rt R
75%
strategy for the synthesis and 1,2-dihydropinidine (eq 28).30
Under sonication conditions, terminal alkynes with protected
Br
hydroxyl groups give Markovnikov addition products predomi-
+
N In, DMF, 16 h N nantly, whereas with unprotected alkynols the regioselectivity is
Cl– 65%
CO2R CO2Ph very much dependent on the distance between the hydroxyl group
and triple bond moiety (eq 32).32c The hydroxyl group is pro-
posed to coordinate with the allylindium reagent. This method
(28) also works with internal alkynols.
N
))) HCl
H OH + Br + In
THF, rt
(±)-Dihydropinidine
OH
(32)

Allylation of Cyclopropene. The coupling of allylic indiums

with cyclopropenes occurs exclusively at the γ-carbon of allylic 85%
 INDIUM 7

Allylation of Allene. Indium-mediated allylindation of O In/H2O

allenols is highly regioselective. The allyl substituent is introduced + Br
R H Y
distal to the methanol moiety (eq 33).33
OH Y OH
+ • (36)
R R
H R5 Y
OH DMF
+
R1 • R3 R4 In2X3 140 °C, 4 h Yield (%)
2
R 3
Y Acetylenic Allenic
H 88 12
R5 R4 R2 R1
(33) Ph 5 95
OH Me 0 100
R3 TMS 33 67
PhMe2Si 20 80

The syntheses of two highly functional fluorinated motifs

TIPSC=CCF2 - and CF2 =C=C(TIPS)-have been reported using
Organoindium Reagents Other Than Allylic Indium. indium chemistry (eq 37).36 Reaction of a difluoroallenylindium
with aqueous HCHO and a Schiff base affords CF2 =C=C(TIPS)
Reformatsky-type Reactions. When imines instead of alde- CH2 OH and β,β-difluorohomopropargylamine, respectively.
hydes are used in the Reformatsky reaction, the resulting amine
intermediate spontaneously cyclizes to give β-lactams (eq 34).34
F F TIPS • F
In/H2O:THF (80:20)
Br F
In
TIPS
R1
R2 TIPS
N In HCHO (5.0 equiv) F
I CO2Et + (34) •
THF, 80 °C N H2O:THF (80:20)
HO F
R1 H 28–60% O R2 rt, 12 h
67%

Propargylic, Homopropargylic, and Allenic Indium

Reagents. The chemistry of alkynyl indium generally parallels F
that of the allylic indium. However, the facile allenic and TIPS F
PhCH2N=CHPh (37)
propagylic isomerism of the homopropargylic indium reagent Ph
leads to mixtures of homopropargylic alcohols and allenic Et2O, rt, 3 days
BnHN
alcohols following reactions with carbonyl compounds (eq 35).35
56%

The homopropargylic gem-difluoro alcohols can also be ob-

O In tained by addition of indium to a mixture of aldehyde and triiso-
+ Br
H15C7 H
DMF propylpropargyl bromide in aqueous media (eq 38).
72%

OH OH
+ (35) F F
• In (1.2 equiv), RCHO
H15C7 H15C7 Br
H2O:THF (80:20)
62:38 TIPS
F
TIPS F (38)
R
High regioselectivity can be obtained in the indium-mediated HO
coupling between aldehydes and propargyl bromide in aqueous
15–86%
media. However, the regioselectivity depends on the substitutent at
the γ-position of the propargyl bromide (eq 36).35 When the parent
propargyl bromide is coupled with aliphatic or aryl aldehydes, the The reaction of 1,4-dibromobut-2-yne with aldehydes in the
homopropargylic alcohols are the major products. In contrast, the presence of indium leads to diene alcohol (eq 39) with yields
major coupling products are allenic alcohols in the presence of ranging and 53–68%.37 The allenylmethyl indium species is pre-
methyl, phenyl, or silyl substituents at the γ-position. sumably formed and subsequently hydrolyzed to the product.
8 INDIUM

OH lithium iodide is critical for good efficiency, and DMF is the sol-
O
In vent of choice. The reactions with other alkenes such as electron-
+ Br Br R (39)
R H H2O, rt rich and non-activated ones proved futile.

CN LiI
R = alkyl, aryl, vinyl 53–68% DMF
COMe + + In
OH Br CN rt
Br
•
R MeOC
CN (43)
In
CN
94%
Indium is also found to mediate the reaction between various
aldehydes and methylpropargyl bromide to give (E)-1-substituted- When the indium carbenoid derived from dibromomalonon-
2,5-dimethylheptatrien-1-ol compounds in moderate to good itrile is treated with both aromatic and aliphatic aldehydes,
yields (eq 40).38 cyanocyclopropanes are obtained in good yields, while ketones
are inert toward this reaction (eq 44). The reaction pathway was
O In proposed to involve alkylidenemalononitrile intermediates. It is
+ R1
1 A or B interesting to note that replacement of dibromomalononitrile with
R H Br
OH H • dibromocyanoacetate affords exclusively oxiranes from aldehy-
A = THF/sonicater des.
B = THF/InBr3
51–75% CN LiI Et
(40) CN
DMF
EtCHO + In + (44)
Br R rt
Br X R
Allenylmethylindium species, which are conveniently prepared
from the respective bromides, are used in additions to various
aldehydes to afford the products in yields of 73–93% (eq 41).39 R X Yield (%)

CN CH2 87
O
• In CO2Et O 62
+
R H Br SiMe3 DMF

R = alkyl, aryl Intramolecular Addition. Several intramolecular versions

of this reaction have been developed for the formation of α-
OH • (41)
methylene-β-butyrolactones42 and for two-carbon ring expansion
SiMe3 (eq 45). In the latter case, the use of water proved to be essential.
R
O
73–93% Br aq HCl
O MeOH DBU
+ In
rt
Benzylindium Sesquiiodide: Carboindation of Alkynes. Ben- CO2Et
zylindium sesquiiodide undergoes carboindation with both inter- CO2Et
nal and terminal alkynes in moderate to excellent yields (eq 42).40
The addition to the terminal alkynes is regioselective at the ter-
O
minal carbon, producing exclusively (Z)-alkenes. However, the
addition to internal counterparts is not as selective. (45)
THF Ph
In + PhCH2Br (PhCH2)3In2Br3
rt CO2Et
50%

Ph Ph (42)

91%
Second Update
Indium Carbenoids. Indium carbenoids can be prepared Michael R. Pitts
from indium metal and dibromomethanes possessing electron- StylaCats Ltd., Runcorn, UK
withdrawing substituents in DMF. The carbenoids lead to cyclo-
propanation when treated with electron-deficient alkenes, gen- Allylations. The now widespread interest in indium metal
erally displaying moderate to high yields (eq 43).41 The use of to mediate the allylation of carbonyl compounds and their like,
 INDIUM 9

originated from its use in the Barbier-type reaction in sugar chem- O

In
istry under aqueous conditions.43 This work by Chan and Li,44 Me
H
+ Me3Si Br
H2O, rt
followed pioneering studies by Araki and co-workers in organic 62%
Me
solvents.10b Indium’s first low ionization potential together with
low reactivity towards water, air, and alkali allow much milder OH
conditions for Barbier–Grignard-type reactions than those devel- Me SiMe3 (49)
oped for zinc and tin. Me
The active organoindium species was thought to exist as the
3:1 E/Z
sesquihalide,1 but recent studies suggest the structure may be
allylindium(I) (3).14a The active species reacts readily with O
In
ketones and aldehydes, but not with the allylic halide itself, thus Me + MeO2C Br
H H2O, rt
avoiding Wurtz-type by-products.
Me 81%

In OH
Me
(50)
3
Me CO2Me
The allylindium species is also unreactive towards ester and 92:8 anti/syn
cyano groups and, due to its low basicity, is compatible with acidic
environments, be it substrate (e.g., 2-(bromomethyl)-acrylic It has been reported that the stereoselectivity of the additions
acid)45 or solvent (e.g., water)8 (eq 46). can be altered by addition of alkoxide ligands.46 Enantiopure
α-hydroxy acids can be accessed via allylation of glyoxyl moi-
eties controlled by a chiral auxiliary such as Oppolzer’s sultam
O
(eq 51).47
In
2 + Br Me Me
R1 R COOH H2O, rt
29−96%
O In, RBr
OH
N THF/H2O
(46) Ar
R1 COOH S 54−98%
R2 O2
O
Me Me

Generally only γ-coupling products are obtained (eq 47) unless HO R

N (51)
the γ-substituent is too sterically bulky (e.g., t-Bu and TMS) (eqs Ar
48 and 49).15a The γ-coupled product is formed even when the S O
γ-substituent is in conjugation, despite the loss of conjugation O2
(eq 50). α,β-Unsaturated carbonyl compounds react exclusively
1,2 but in the presence of TMSCl give only the 1,4-adduct.18 Use of the chiral ligand cinchonidine induced a degree of enan-
tioselectivity in the allylation reaction (eq 52).26b
Me Br OH
O
Me Br In Me
+ PhCHO Ph (52)
Ph H H2O, rt In, (−)cinchonidine Me Me
Me 90% THF/hexane
99% 90% ee
OH
In the allylation of azetidin-2,3-diones, indium gives a single di-
Ph (47)
astereomer in higher yield than the analogous zinc addition which
Me Me offers no stereocontrol (eq 53).48 A comprehensive account of the
diastereoselectivity of indium-mediated allylations is provided by
Paquette et al. who studied a range of substrates designed to ex-
O amine co-ordination effects.10e
Me In
H + t-Bu Br O Ph OH
H2O, rt In Ph
Me + Br
87%
N H2O/THF
rt N
O R O R
80−98%
OH
Me t-Bu (48) (53)

Me Indium-mediated allylation in water proceeds at room tem-

8:2 E/Z perature and doesn’t require a cosolvent, whereas zinc and tin
10 INDIUM

usually require acid catalysis, heat, or sonication. However, during O OH

Br In
a thorough examination of indium-mediated allylations in water, + R1
Whitesides et al. discovered that the use of weak hydrochloric acid R1 H H2O, rt
50−97% (60)
as solvent increased the reaction rate.49 Compared to tin-mediated
allylation, the products from carbohydrate substrates were cleaner OH
with indium and gave higher diastereoselectivities. This method O R2
In
was applied to the homologation of sugars.50 + Br R1
R1 H H2O, rt
Indium-mediated allylations have been extended to the R2
60−99% (61)
formation of allylic ketones from acyloyl-imidazoles and
-pyrazoles (eq 54).51 With acyloylimidazoles some reduction to
the alcohol occurred, whereas no reduction was observed with Indium mediates a complimentary Barbier-type reaction with
acyloylpyrazoles. alkynyl halides and aldehydes to give propargyl alcohols.57 A mix-
ture of alcohol and ketone was obtained with the latter increasing
O
R2 X In with increasing aldehyde concentration (eq 62). A disproportiona-
+
R1 Het H2O, rt tion between the indium alkoxide intermediate and benzaldehyde
R3 85−95% was therefore postulated to explain the oxidation.
O
I In, CH2Cl2
(54)
R1 PhCHO +
Ph then H2O
R2 R3
A B
Het = N N N
or
OH O
+ Ph (62)
In addition to aldimines,7 indium also mediates the allylation Ph
Ph Ph
of hydrazones (eq 55), aldonitrones (eq 56),52 oximes (eq 57),53
C D
pyridinium salts (eq 58),29b and activated nitriles (eq 59).54 Use
of indium catalytically, with electrochemical regeneration of the A B C D
active species, has been employed for these reactions.55 1 equiv 2 equiv 70% <1%
2 equiv 1 equiv 35% 65%
NHAr′ Br NHAr′
N HN
(55)
In, DMF/H2O, rt Analogously to allylations, indium metal mediates
R1 Ar
75−90% R 1
Ar Reformatsky-type reactions of α-halo esters with carbonyls
giving β-hydroxy esters. The reaction was originally carried out
Ph O
Ph OH by Chao and Rieke who proposed a classical mechanism,2 later
N Br N
(56)
work suggested indium sesquiiodides as the active species from
Ar H In, DMF/H2O, rt Ar α-iodo esters and commercial indium powder.58 Rieke indium (∼
75–90% 4.0 μm particle size) allowed the use of α-chloro esters. Despite
long reaction times in some cases it is worth noting a wide range
OMe OMe
N HN of aldehydes and ketones react (eq 63). α,β-Unsaturated carbonyl
Ph Br compounds give exclusively 1,2-addition products (eq 64). No
H (57) elimination to α,β-unsaturated esters occurs and hydroxyl groups
In, H2O, rt
N N Ph do not require protection.
60%

99:1 syn/anti
OH
CHO EtO2C I CO2Et
Br
(63)
(58) In, THF, rt
N Cl In, DMF N OH 67% OH
65%
CO2Ph CO2Ph
OH
EtO2C I
CN I H2N
CHO CO2Et (64)
Ph In, THF, rt Ph
In, THF, rt (59)
Ph CO2Et 89%
65% Ph CO2Et

The use of propargyl halides has also been examined with prop-
2-yn-1-yl bromide giving the homopropargyl alcohol on reaction
with aldehydes (eq 60), whereas γ-substitution led to allenylic
alcohols (eq 61).34b The propargylation works equally well for
imines and imine oxides.56
The Reformatsky reaction has been carried out with some de-
gree of stereocontrol by the use of chiral ligands.59 Cinchonine
and cinchonidine gave the best results of 40–70% ee for the result-
ing β-hydroxy esters (eq 65). These chiral amino alcohol ligands
are incompatible with zinc in place of indium.
 INDIUM 11
OH NO2
CHO EtO2C I CO2Et H
N In, NH4Cl
(65) Me
In, cinchonine EtOH/H2O
THF/pentane 71% ee S 65%
R Br
63%
NH2
H
Bromoacetonitriles can be coupled with aromatic acyl cyanides N
to give α-cyano ketones with indium. No additives are required, Me (69)
however sonication is necessary for good yields (eq 66).60 S
R Br

O
O R In, NH4Cl
R
Br CN In, CN
+ Ar (66) (70)
Ar CN THF NO2 MeOH/H2O N
R 60−86% R 69−89% OH
R = H, Me
Indium-mediated reduction of aromatic nitro compounds has
been utilized in the preparation of tetrahydroquinolines (eq 71),67
A range of substituted aromatic, activated chlorodifluoromethyl and 2,1-benzisoxazoles (eq 72),68 under aqueous conditions.
compounds were added, in a Reformatsky-type reaction, to
heteroaromatic aldehydes to give the difluoromethylene product NO2 O In, HCl (aq)
(eq 67).61 Indium is assumed to generate the enolate. R +
25–87%

R
O In O
+ ArCHO
H2O/THF
N CF2Cl rt R (71)
H 54−86% OH
N
R H

X
N OH Me Me
(67) R2 In
H R1 +
Br NO2 MeOH/H2O
O Ar NO2 50−97%
F F
X = O, NPh
R2
Reductions. Indium has a first electrode potential of 5.8 eV,
R1 O (72)
similar to that of the alkali metals, e.g., sodium (5.1 eV), lithium
N
(5.4 eV), and much less than that of other common reducing met-
als such as zinc (9.4 eV), magnesium (7.7 eV), or tin (7.3 eV).
The nitro reduction methodology was also extended to the gen-
These values suggest indium is a good single-electron transfer
eral reductive removal of the 4-nitrobenzyl oxygen-protecting
agent, with a range of useful reductions demonstrated even under
group (eq 73).69 Mechanistic studies showed this reaction to
aqueous conditions. Indium metal in water or an organic solvent
proceed via the aniline, which activates the benzylic bond to-
with a suitable proton source (e.g., ammonium chloride, acetic
wards the addition of an electron. The 4-toluidine by-product is
acid) has been used in a variety of selective reductions.62
simply removed by an aqueous wash. The trichloroethoxy car-
Mild reduction of aryl nitro compounds to anilines is achieved
bonyl and trichloroacetyl protecting groups (eq 74),70 and one t-
in refluxing aqueous ethanolic ammonium chloride, a method that
butoxycarbonyl group of a bis-protected amine (eq 75),71 are also
can tolerate functionality such as iodides, cyano groups, and ke-
reductively cleaved via indium-mediated single-electron transfer.
tones that are sensitive to hydrogenation (eq 68).63 The presence
In all cases indium-mediated conditions have the advantage of
of sulfur does not affect the reduction and sensitive protecting
being mild enough to leave acid sensitive protecting groups
groups such as mesyl are unaffected.
intact, such as THP, TBDMS, and TBDPS.
In, NH4Cl R
R NO2 R NH2 (68) O ROH
EtOH/H2O
60−98% NO2
In, NH4Cl
O or or (73)
Indium has been shown to be the only method sufficiently mild EtOH/H2O
61−100%
in certain cases (eq 69),64 and has also been used for nitro reduc- R O O
tion on a significant scale.65 Reduction of nitrostyrenes leads to
NO2 R OH
oximes (eq 70).66
12 INDIUM

O The saturation of the hetero-ring in nitrogen containing hetero-

In, NH4Cl
R
X O CCl3 MeOH/H2O
RXH (74) cycles has also been demonstrated (eq 81).80 The transformation
66−98% is very clean and difficult to perform with other methods.
X = NH, O
In, NH4Cl
NHBoc R R
N(Boc)2 In, MeOH EtOH/H2O
OMe OMe (75) N N
83−92% R 25−76% H
R
O O
In, NH4Cl
R R (81)
Indium has been used in the reduction of azides (eq 76)72 and N EtOH/H2O NH
oximes73 to amines; the reactions proceed in better yield and 71−97%
shorter times than the analogous zinc reactions. In both cases the H
N N
resulting amine can be protected in situ (eq 77),74 as compared to In, NH4Cl
R R
the amine generated by nitro reduction.75 Azide and nitro reduc- EtOH/H2O
tion with indium has been demonstrated on solid support.76 N N
90−92%
H
In, NH4Cl
R N3 R NH2 (76) For many of the reductions described, catalytic amounts of in-
EtOH/H2O
86−94% dium (∼ 5 mol %) together with an excess of a coreducing metal
such as zinc, provides identical results.
R1 OH In, Ac2O R1
N NHAc (77) Reductive Couplings. Indium mediates the pinacol cou-
AcOH/THF
R 2
65−100% R2 pling of aromatic aldehydes in aqueous media, under sonication
c.f. nitro and azide (eq 82).81 The yields of the 1,2-diols were moderate to good, with
varying d,l/meso ratios. The reactions were very slow and low-
The deoxygenation of amine-N-oxides by indium in aqueous yielding in the absence of sonication.
media has also been reported.77 Similarly, hydroxylamines can
be reduced quantitatively to the corresponding amine (eq 78).78 CHO In
R
In, NH4Cl H2O/t-BuOH
Ph N Ph Ph N Ph (78) 50−83%
EtOH/H2O H
OH 100%
OH
R
Reductive elimination of halohydrins to alkenes is possible with (82)
indium in the presence of catalytic amounts of indium trichloride R
OH
and tetrakis(triphenylphosphine)-palladium(0) (eq 79).79 Zinc, in
place of indium, yielded only debrominated material, whereas tin
gave no reaction. Analogously, reductive coupling of aromatic aldimines to the
vicinal diamines occurs in very good yields under straightforward
OH conditions (eq 83). An equal mixture of d/l and meso diastereoiso-
R2 In, InCl3, Pd(PPh3)4 R2 mers is generated suggesting a fast coupling step.82
R1 R1 (79)
THF/H2O, rt
X
34−98% Ar2HN Ar1
Ar1 N In, NH4Cl
2 (83)
Ar
Comparatively trihalomethyl carbinols, as well as their EtOH/H2O
H 40−100%
Ar1 NHAr2
acetates, mesylates, and tosylates, are reduced to vinylidene
dihalides with indium. Studies of the naked carbinol under aque-
ous conditions gave a mixture of the vinylidene dihalide and the Symmetrical 1,2-diketones can be prepared by indium-
dihalomethyl carbinol, but reduction of the activated carbinols mediated reductive coupling of acyl cyanides (eq 84).83
proceeded smoothly in DMF (eq 80).
O O
In
OH OH R (84)
In, NH4Cl 1
X R CN DMF R
+ R 60−80%
R1 CX3 EtOH/H2O, reflux R1 CHX2 O
X
32−40%
Iodo compounds can be homocoupled in the presence of indium
OR2 metal in DMF.84 The reactions presumably proceed via radicals
In X
R1 (80) with dehalogenation favored in some cases.85 Alkyl and aryl io-
R1 CX3 DMF, reflux
60−97%
X dides were reductively coupled to give bialkyls and biaryls, and
α-iodoketones could also be coupled in this manner to produce
R2 = Ac, Ms, or Ts 1,4-diketones (eq).77
 INDIUM 13
In R R
Me(CH2)14CH2I DMF
Me(CH2)30Me
92% I
In, I2
MeOH
(88)
R R O O O O
In 60−73%
(85)
DMF
I 78−82%
R
Cross-coupling Reactions. Organoindium reagents can be
prepared where three alkyl or aryl groups are attached to the
O O
In metal. These can be prepared by transmetalation with indium
I DMF
Ph or preferably an indium halide. By analogy with organoboranes,
Ph Ph
60%
O organoindium compounds can undergo transition metal catalyzed
cross-coupling reactions.
Allylindium compounds prepared in situ from the allyl halide
The latter reaction had been previously observed by Araki when also undergo cross-coupling, and thus offer an especially mild
investigating the mediation of aldol condensations between α-halo method for C–C bond formation. Early attempts at this cross-
ketones and aldehydes by indium and indium(I) iodide (eq 86).86 coupling led instead to the discovery of a deoxygenative, highly
The reactions proceeded via generation of the indium enolate in substituted cyclopropane-forming reaction (eq 89).91 These prob-
situ. lems have been overcome and a variety of allylindium reagents92
have been coupled with a wide range of organic electrophiles
O
(eq 90).93
In
Br + Me(CH2)6CHO
Me DMF
R4 R4
54%
Br R3 R1
R3 R1 In
R4
O R2
(86) THF
R2 O then H+ (+/−)
Me (CH2)6Me
49−92%
(89)

The use of indium for the cross-aldol reaction with a secondary R3 R3

In
α-bromoketone and an aldehyde shows a significant increase in R1 I R1 In
DMF
diastereoselectivity, compared with tin or zinc.87
The single-electron transfer properties of indium have been R2 R2
further explioted to generate radicals for addition reactions in R2
water. In this way simple iodoalkyls were added to electron- X
deficient double bonds,88 and extended to cyclization-trap reac- R R1
R
tions (eq 87).89 R3
R3
R1 In R3
In InI R R (90)
R2 R1
X
70−97%
RI R R2
H2O
R R3
R MeO2C NHNPh2
MeO2C NNPh2 R X R1
48−98%
R
R2
R R
PhO2S PhO2S (87)
61−86% Triorganoindium compounds (generally prepared from InCl3
and the corresponding Grignard or organolithium) can also be
R I used as the nucleophile in the coupling with nickel substituted
R for palladium (eq 91).94 The couplings also proceed in aqueous
O N 42−84% O N
media.95
CHPh2 CHPh2 Pd cat
InR3 + 3 R1X 3 R R1 (91)
THF
82−97%

Reductive radical cyclizations with alkynes have also been uti- R1 = Ar or vinyl
lized in the synthesis of active HIV protease inhibitors.90 Catalytic
amounts of indium (10 mol %) and iodine (5 mol %) promote
the atom-transfer 5-exo cyclization to alkenyl iodides (eq 88). Miscellaneous. The cyclopropanation of alkenes with methy-
Increased amounts of indium and iodine yield the reduced exo- lene dibromides is mediated by indium in the presence of lithium
cyclization product. iodide (eq 92).96
14 INDIUM

In, LiI E1 Indium generates phenacyl sulfides from α-bromoketones and

Z + Br2CE1E2 (92) sodium alkyl thiosulfates in water (eq 98).100 A similar reaction
DMF
E2
20−100%
Z with diselenides produces α-selenoketones.101
E1 = E2 = CN or CO2Et

O
Electron deficient alkenes give good to moderate yields, Br + PhCH2SSO3Na
In
whereas alkenes with nonactivating substituents (Z), do not show Ph H2O/THF
any reactivity. 80%
Aldehydes and ketones react with dibromomalonitrile in the O
presence of indium and lithium iodide to give tetracyanocyclo- SCH2Ph (98)
propanes in a novel Wideqvist-type process (eq 93). The reaction Ph
appears to involve indium carbenoids. In an unexpected reaction,
the use of ethyl dibromocyanoacetate in place of dibromomaloni-
trile provides the corresponding oxirane (eq 94). Michael addition of allyl bromide to 1,1-dicyano-2-arylethenes
proceeds smoothly with indium in an aqueous media (eq 99).102
CN
In, LiI CN
PhCHO + Br2C(CN)2 NC (93)
DMF
95% CN Br CN
Ph CN In
(99)
H2O/THF
Ar CN Ar CN
In, LiI CN 65−82%
O
EtCHO + Br2C(CN)CO2Et (94)
DMF
62% CO2Et
Et
Indium metal catalyzes Friedel-Crafts aromatic allylation in the
presence of calcium carbonate and molecular sieves (eq 100).103
Control of syn/anti ratios in indium-promoted C–C coupling is The reactions are regioselective for the α-position and are straight-
possible with α-chlorosulfides.97 Addition to aldehydes proceeds forward to perform. The indium catalyst is recyclable and pre-
smoothly in aqueous systems to give the predominantly anti prod- sumed to act as a Lewis acid.
uct which can be used to gain access to stereocontrolled epoxy
alkynes in good yields (eq 95). Addition of indium trichloride as
a Lewis acid gives the reverse stereochemistry (syn over anti) via Me Me
a chelated intermediate.
Me Cl
(100)
Ph In (0.1 equiv)
S 1. In, H2O/DMF O CaCO3, 4 Å mol sieves
RCHO + 75%
2. Me3O+BF4− 1:1 ortho/para
Cl R
CH2Cl2
85−90% 20:80 syn/anti
(95)

Ethyl bromoacetate adds to imines in the presence of indium to Third Update

give 3-unsubstituted β-lactams (eq 96).98
Angel Resendez, Chris L. Murphy, & Rachel Snelling∗
Ar Ar University of California, Santa Cruz, CA, USA
In, BrCH2CO2Et
(96)
N THF, 80 °C N Allylations. An asymmetric allylation of aldehydes has been
R 28−60% O R developed by Singaram and coworkers under Barbier-type con-
ditions utilizing indium, allyl bromide, and an amino alcohol
R = Ar, CH2Ar, CH2CH=CH2
chiral auxiliary.104,105 Using the chiral amino alcohol (1S,2R)-
(+)-2-amino-1,2-diphenylethanol [CAS 23364-44-5], up to 99%
Indium metal also mediates the coupling of alkyl bromides with conversion can be achieved affording the (S)-enantiomer of the
aromatic sulfonyl chlorides to give the corresponding sulfones corresponding homoallylic alcohols with excellent enantiomeric
(eq 97).99 The reaction proceeds in water. purity. While a wide variety of aldehydes can be successfully
used as substrates, ketones afforded the corresponding tertiary
homoallylic alcohols with diminished enantioselectivity. Density
In, H2O
R1SO2Cl + R2X R1SO2R2 (97) functional theory calculations have been reported to rationalize
45−84%
the stereoselectivity (eq 101).106
 INDIUM 15
HO NH2 O O O

H In(0), O , Br
O Br
In(0), Py, , THF/n-hexane, –78 ºC, 50 min, 96%
OCH3
H THF/n-hexane, –78 ºC, 1.5 h
X 90–97% yield, 76–93% ee O

X = H, m-CH3, o-Cl, p-CN O

(103)
OH

(101) OCH3
X
Loh et al. have reported a highly regioselective indium-
mediated crotylation in aqueous media to produce substituted
homoallylic alcohols.16c By changing the solvent or concentra-
tion, one can manipulate the regioselectivity of the product. Pure
γ-product can be obtained in 95% yield by using 1:1 ratio of
Singaram and coworkers have reported the asymmetric addi- THF:H2 O and 6 equiv of solvent to 1 equiv of the substrate. When
tion of allyl, methallyl, and propargyl groups to aldehydes and 6 equiv of H2 O to 1 equiv of substrate was used, essentially pure
ketones using B-chlorodiisopinocampheylborane (d DIP-Cl), α-product was obtained in 85% yield. Prior to this example, the
indium metal, and allyl, methallyl, and propargyl bromides.107 α-homoallylic alcohols had only been reported with the use of
Under Barbier-type conditions, indium promotes the transfer of bulky aldehyde groups (eq 104).
allyl, methallyl, and propargyl groups to the B-atom of d DIP-Cl
forming the corresponding chiral borane reagents. These chiral O H In(0)
borane reagents, formed in situ, then react with aldehydes and +
c-C6H11 H H2O, rt, 24 h
Br
ketones to give the homoallylic and homopropargyl alcohols in 85% (99:1 α:γ), (70:30 E:Z)
high yields and with excellent enantioselectivity (up to 98% of
the (S)-isomer). This is the first example of direct synthesis of OH OH
substituted allylboranes from the corresponding substituted allyl + (104)
bromide using indium and d DIP-Cl (eq 102). c-C6H11 c-C6H11
H H

Indium-mediated allylation of imines was recently reported.109

This reaction utilizes indium metal, allyl bromides, and aldimines
to generate homoallylamines in excellent yields under Bar-
BCl bier conditions. Using (+)-cinchonine as a chiral auxiliary, the
O
2
Allyl bromide homoallylamines can be generated with 22–44% ee (eq 105).
BR R1 R2
In0 + or 2
THF
Propargyl bromide R2 In(0)
N + Br
R = allyl or allenyl R1 THF, rt, 2 h
75–97%

R2 OH R2 OH R1 = H, R2 = H
* or * (102)
R1 Allyl R1 Propargyl R1 = 4-isopropyl, R2 = H
R1 = H, R2 = 2-methoxy
R2 = H up to 98% ee
R2 = CH3 up to 94% ee R2
(105)
N
R1 H

Welch and coworkers have shown that difluoroacetyl trialkyl

Homoallyl esters can be generated from aromatic aldehydes
in a one-pot, three-component tandem reaction as shown by
Du et al.108 This reaction tolerates electron-donating, electron-
withdrawing substituents and heteroaromatic groups on the alde-
hyde. The authors report that aliphatic anhydrides are more suit-
able for this reaction compared to aromatic anhydrides. This
method uses the relatively nontoxic metal indium, short reaction
times, affording the products in excellent yields (eq 103).
silanes can produce the corresponding homoallylic alcohol via an
indium-mediated pathway.110 Under the reported reaction con-
ditions, the normally observed Brook rearrangement does not
occur. This allylation reaction requires a mixed solvent system
containing THF and water as the solubility of difluoroacetyl
trialkyl silanes decreases in aqueous media. Substituents on the
silicon have no effect on the product formation, Substituted allyl
bromide groups did not give the desired product (eq 106).
16 INDIUM

O organic solvents as the best solvent system for this reaction is a

In(0)
Ph Br 1:1 mixture of THF:H2 O (eq 109).
HF2C Si + THF : H2O (1:1), rt, 0.5 h
Ph
tBu 84%
Ar In(0)
N
OH + Ph Br
HF2C THF : H2O (1:1)
(106) H COOEt rt, 12 h
Ph Si 48–96%, >95:5 syn:anti
E-geometry
Ph tBu

Kim et al. demonstrated the regioselective monoallylation H NH-Ar H NH-Ar

of 1,5-dicarbonyl compounds using indium metal and allyl
bromide.111 The authors show that various 2,3-dihydro-4H-pyran-
4-ones, 3,4-dihydro-2H-[1,4]oxazines, and 3,4-dihydro-2H-
pyrans can be synthesized through sequential indium-mediated
Barbier-type allylations followed by acid-catalyzed dehydrative
cyclization. When the reaction is carried out using crotyl bromide
under the same reaction conditions, the product is obtained in a
62% yield with a 2:1 syn:anti selectivity (eq 107).
1. In(0)
O O O THF, reflux, 5 h
+ Br
2. p-TsOH (20%)
benzene, reflux, 1 h
64%
O X-ray structure (eq 110).
* * COOEt + * * COOEt (109)
Ph H Ph H
syn anti
Baba and coworkers have reported the stereoselective
cinnamylation of N-aryl α-imino esters.114 The two contiguous
stereocenters can be generated through a chelation-controlled
indium-mediated reaction under Barbier-type conditions.
Electron-donating, electron-withdrawing, or heteroaromatic
substituents on the imine group are tolerated. The reaction
proceeds in ethanol and is completed in 6 h at 30 ◦ C. This
reaction is highly diastereoselective favoring the syn-isomer. The
stereochemistry of the major isomer was assigned based on the

(107) Ar
N In(0)
+ ROOC Br
O EtOH, 30 ºC, 6 h
EtOOC H 50–71%, 98:2 syn:anti
E-geometry
Minehan and coworkers have reported the allylation of d- R = Et
glyceraldhyde acetonide [CAS 15186-48-8] with 2,3-dichloro-1- R = Me
propene [CAS 78-88-6] to give the corresponding homoallylic al-
cohol in 92% yield with a diastereoselectivity of 7:1.112 The major H NH-Ar H NH-Ar
isomer was assigned the anti-stereochemistry, which is analogous * * COOEt + * * COOEt (110)
to other reports of allylation of glyceraldehyde. The vinyl chlo-
ROOC H ROOC H
ride moiety in the products can act as a handle for further chemical
syn anti
transformations, such as cross-coupling reactions (eq 108).

Kim et al. have shown that ortho-cyanobenzamide can undergo

O In(0)
allylation of the nitrile group under Barbier-type conditions.115
O + Cl They reported that cyano group is readily attacked by allylindium
H DMF
Cl reagent to form an imine intermediate. The imine intermediate re-
51–88%
O acts further with the amide group generating the substituted quina-
zoline derivatives (eq 111).

O (108) Ph O
O
NH In(0), Br N Ph
OH Cl (111)
THF, reflux N
60–75%
N
Baba and coworkers have reported the chelation-controlled
Barbier-type indium-mediated addition of γ-substituted allylic
halides to N-aryl-α-iminoesters with high diastereoselectivity.113 Kim et al. also reported the generation of fully substituted
The new C–C bond formation produces two contiguous stereocen- 4-alkenylimidazole starting from N-(cyanoalkyl)-amides.116a–d
ters favoring the syn-isomer. The imine can be substituted with aro- The allylation of the nitrile proceeds smoothly under Barbier-
matic functional groups containing electron-donating, electron- type conditions, followed by subsequent dehydrative cyclization.
withdrawing, or biaryl systems. This reaction is efficient in con- This reaction is very general and tolerates aliphatic or aromatic
structing N-aryl α-amino acid derivatives without the need for dry substituents on the amine (eq 112).
 INDIUM 17

O Ph O BPin In(0) (10 mol %)

R In(0), Br +
Ph R N N R1 R2 CH3 H2O (1 M) 0–10 ºC
N (112) 20–48 h
THF, reflux
72–99%, >99:1 α:γ
Ph CN 21–59% Ph R1 = Ph, R2 = Me
R = Ph, Cy, Bn R = α-tetralone
OH OH
R2 R2
In a stereoselective total synthesis of tubulysin V, Lin and + (116)
R1 R1
coworkers used an indium-mediated allylation to synthesize the
CH3 CH3
desired (R)-diastereomer (S)-N-tert-butane-sulfinyl imine in 76%
syn anti
yield and 92% de (eq 113).117

O O
Propargylations. Singaram and coworkers have further
In(0), Br
N S HN S (113) extended the utility of indium in chiral auxiliary-mediated
NaBr (sat.) asymmetric synthesis by demonstrating an enantioselective
76%, 92% de
propargylation of aromatic aldehydes and ketones.120,121 In the
case of the aromatic aldehyde, the homopropargylic alcohol can
be achieved with yields in the range of 53–90% and ee values up
Auge et al. have reported the allylation of ketones with allyl to 95% (eq 117).
bromides using indium metal as a catalyst.118 The regeneration
of active indium in this allylation reaction was achieved using a HO NH2
mixture of Mn/TMSCl. The authors suggest that manganese could
be acting as a terminal reductant regenerating the active indium Br
O In(0), Py, ,
metal. These reaction conditions work for both aldehydes and
ketones (eq 114). R H THF/n-hexane, –78 to 25 ºC, 16 h
53–90%, 74–95% ee
O R = tBu, Ph
In(0) (0.1 equiv) OH
+ Br R1 (114) OH
R1 R2 Mn/TMSCl, (117)
R2
rt, 3–16 h R *
32–91%
R1 = Ph, R2 = H
R= (CH2)5 For ketones, essentially quantitative conversions were achieved;
R1 = CH3CH=CH, R2 = H however, a 1:1 mixture of the homopropargylic alcohol and allenic
alcohol was obtained as the product (eq 118).
This reaction gives rise to the anti-isomer, arising from a HO NH2
nonchelation-controlled transition state. The Felkin–Anh model
shows the increased stabilization addition of the nucleophile O
(eq 115). Br
In(0), ,
CF3
Ti(i-PrO)4, THF, 25 ºC, 24 h
OBn 100% conversion, 1:1 products
O

BnO (115) HO CF3 HO CF3

InCl2 OH
* + * (118)
H H

Another catalytic indium-mediated carbon–carbon bond for-

mation was reported by Kobayashi and coworkers.119 In order
for the allylation to proceed smoothly, water is required. The in-
dium catalyst can be recovered and reused without any loss of
activity. This reaction demonstrates high regio- and diastereose-
lectivity of asymmetric catalysis in water using the chiral auxiliary
bis(oxazoline) ligand. The regiochemistry depends on the substi-
tution of the R1 and R2 groups. In most cases, the syn-isomer
is observed; however, when R1 and R2 are 2-MeO-C6 H4 and
Me, respectively, the anti-isomer is the major product. The au-
thors suggest that the reaction mechanism proceeds through a
single-electron transfer triggering the formation of the reactive
allylindium(I) at the metal surface through catalytic transmetala-
tion (eq 116).
Lee et al. have reported the Michael addition of propargyl/
allenyl indium to α,β-enones.122 The indium reagent is generated
under Grignard conditions from indium and 1-bromo-2-butyne
[CAS 3355-28-0]. Successive additions of the enone and TMSCl
are necessary to give the Michael addition products in good yields.
The role of TMSCl is not fully understood; however, it may be
activating the carbonyl group (eq 119).
O O
Br
H3C In(0), TMSCl
+ (119)
25 ºC
82%
18 INDIUM

Uziel and coworkers have shown that indium-mediated alkyny- Br

lation of simple carbohydrate derivatives can readily generate sev- In(0)
eral C-glycosides.123 Sugar derivatives with an acetyl group at X (123)
X THF:H2O (1:1), rt, 16 h
the anomeric position were tested as potential electrophiles for 62–75%
the indium-mediated alkynylation under Barbier-type conditions.
Both pyranosyl and furanosyl carbohydrates were studied, leading X = O, C(CO2Me)2
to diastereomeric mixtures favoring the β-anomer. For carbohy-
drates bearing an oxygen atom in the C-2 carbon atom, nonpartic-
ipating groups, such as acetonide or benzyl groups, are required In 2008, Shanthi and Perumal have reported the indium-
for this indium-mediated C-glycosylation (eq 120). mediated, three-component, one-pot synthesis of 4-allyl-2-amino-
4H-chromenes starting from salicylaldehyde [CAS 90-02-8],
malononitrile [CAS 109-77-3], and allyl bromide [CAS 106-95-
AcO
O In(0) 6].127 Apparently, this is the first example of using indium for
OAc + I Ph
CH2Cl2, reflux the synthesis of substituted 2-amino-chromenes. This reaction is
PGO 44–96% very simple, proceeds smoothly in water, and achieves yields in
80% or higher, thereby demonstrating its utility in green chemistry
(eq 124).
AcO
O Ph
(120)
CHO CN In(0), NaI
PGO + + Br
H2O, 1 h
OH CN 80%

Cyclizations. Togo and coworkers have reported that a ring

expansion of α-iodomethyl cyclic β-keto esters can be mediated
through indium metal and a solvent mixture of 1:1 tert-amyl
CN (124)
alcohol (tAA) and water.124 The authors suggest that this ring
expansion reaction proceeds through either a 3-exo-trig or 5-exo-
trigcarbon-centered radical cyclization. This indium-mediated O NH2
ring expansion is advantageous over reactions involving toxic tin
reagents and/or benzene solvent (eq 121). Another interesting indium-mediated cyclization is the gener-
ation of substituted indoles reported by Kim et al.128 These au-
O O thors have developed a simple and efficient, indium-mediated,
I
In(0)
CO2Me
one-pot procedure to generate 2-arylindoles in good yields. Cat-
CO2Me
tAA:H2O (2:1), 2 h (121) alytic amounts of quaternary ammonium salt, Aliquat 336 [CAS
74% 5137-55-3], is necessary to achieve high yields. The authors sug-
gest that this unique cyclization reaction involves the reduction of
the nitro group followed by intramolecular 5-endo-dig cyclization
In 2004, Lee et al. reported an indium-mediated cycliza- (eq 125).
tion reaction to form substituted pyrrolidine and piperidine ring
systems.125 This reaction can be carried out at room temperature In(0), HI (aq.), Aliquat 336 (1 drop)
when KI is used as an additive. Without KI, the reaction requires H3C
benzene (15 mL), reflux, 8 h
reflux conditions. Further studies are underway to explain the
50%
reaction mechanism (eq 122). NO2

Br (125)
In(0), KI H 3C N
Ts N (122) H
DMF, rt, 2 h
Ts N
83%

Reactions with Baylis–Hillman Adducts. Kim et al. have

Elaborating on Lee et al.’s work, Salter and coworkers have
expanded this intramolecular cyclization reaction to oxygen-
containing heterocycles as well as to electron-withdrawing group-
containing carbocycles.126 Salter and coworkers have shown that
this reaction can be carried out in a 1:1 mixture of THF:H2 O. This
reaction pathway proceeds smoothly at room temperature even
without the addition of KI. This reaction is particularly attractive
because it is operationally simple, clean, and provides a useful
contribution to the growing field of green chemistry (eq 123).
developed an efficient synthetic method for the synthesis of
diallylated δ-valerolactam and γ-butyrolactam derivatives via an
indium-mediated successive double Barbier-type allylation.129
The starting materials for this cyclization are readily obtained
from the Baylis–Hillman adducts. In this reaction, allylindium
reagents add selectively to the nitrile and imines. The synthetic
usefulness of the diallyl products was demonstrated by carrying
out further transformations, such as Grubbs’ ring-closing metathe-
sis (eq 126).
 INDIUM 19
COOEt the air and moisture stability of indium. Moreover, indium is rela-
C5H11 In(0), Br
tively nontoxic and tolerates a variety of functional groups on the
CN K2CO3, CH3CN, rt, 2 h
61%
diselenide and/or the acyl chloride coupling partner (eq 129).
COOMe
O O In(0)
Se
+
C5H11 NH Se CH2Cl2, reflux, 12 h
(126) Ph Cl 80%

O
MeO O
Se (129)
Yadav et al. have reported indium-mediated alkynylations of
Baylis–Hillman acetates.130 This reaction produces 1,4-enynes in
high yields with (E)-stereoselectivity through an SN 2 -type allylic
substitution. The presence of catalytic InBr3 (10%) gave the enyne Miscellaneous. Loh and coworkers have shown that Barbier-
products in an 8:2 ratio favoring the (E)-isomer. In the absence of type alkylation of carbonyl compounds in water using unactivated
InBr3 , the mixture of products is obtained in a 1:1 ratio (eq 127). alkyl halides is possible.133 This reaction needs to be carried out
I in water in the presence of three reagents: indium metal, CuI [CAS
OAc 7681-65-4], and I2 [CAS 7553-56-2]. When indium is not present,
CO2Me
In(0)/InBr3 the reaction does not proceed; and when CuI and I2 are not present,
+ the reaction yields are very low. When this reaction is carried out
CH2Cl2, reflux, 7 h
85%, 80:20 E:Z in organic solvent or used as a cosolvent, the reaction proceeds
sluggishly. The authors suggest that this reaction proceeds through
a radical mechanism (eq 130).
CO2Me Ph
O
+ (127) I In/CuI/I2
H + H2O, rt, 48 h
CO2Me
86%

OH

Preparations of Selenides. Jang and coworkers have shown
that alkylphenyl selenides can be generated in a one-pot reaction
using indium metal.131 This reaction shows selectivity for tert-
alkyl, benzylic, and allylic halides over primary and secondary
alkyl halides. The authors suggest that a plausible mechanism for
this reaction begins with indium metal reacting with the diselenide
to generate In(SePh)3 , which in turn can react with the alkyl halide
to generate a carbocation-like intermediate. The intermediate then
reacts with a nucleophilic phenyl selenide to produce the alkyl
phenyl selenide via an SN 1 pathway (eq 128).
(130)
Murphy and coworkers have shown that deoxygenation of epox-
ides can be carried out using indium.134 They propose this reaction
goes through a single-electron transfer initiated by indium metal.
It is plausible that the first step of the reaction goes through a
single-electron transfer from the indium to the carbon–oxygen
bond; however, the exact mechanism is not known (eq 131).
O
In(0)

In(0) EtOH (98%), NH4Cl,

Se
80 ºC, 96 h
tBuI + Se CH2Cl2, reflux, 1 h
92%
99%

(131)
Se (128)

Lin and coworkers have reported the preparation of allenes

Selenol esters can also be generated in a one-pot synthesis as
demonstrated by Braga and coworkers.132 This method can toler-
ate a variety of functional groups within the diphenyl diselenide
[CAS 1666-13-3] and the acyl coupling partners, such as benzoyl
chloride [CAS 98-88-4]. This method is useful for a variety of
reasons, including the ready availability of acylating agents and
using indium-mediated dehalogenation in aqueous solution.135
This is a very simple and efficient method for the synthesis of var-
ious allenes from the corresponding vicinal dihalides. The authors
propose the mechanism involves the generation of the correspond-
ing allylic radical followed by β-halide elimination to produce the
allene (eq 132).
20 INDIUM
In(0)
I In(0)
Br THF : H2O (4:1), rt, 12 h
O 91%
O
The first synthesis of unsymmetrical diaryl amines from aryl
boronic acids and azides has been reported by Reddy et al.136 This
example uses azidobenzene [CAS 622-37-7] and phenyl boronic
acid [CAS 98-80-6]. In the presence of methanol, this reaction
proceeds smoothly to produce a variety of unsymmetrical diaryl
amines. This is an one-pot synthesis and requires both indium
metal and copper(II) acetate [CAS 142-71-2]. The reaction tol-
erates aryl azides with electron-donating groups and heteroaryl
boronic acids. The reaction does not proceed when the aromatic
azide contains halide substituents. Aliphatic azides are sluggish;
however, aromatic azides work well. The authors suggest that the
reaction begins with an indium-mediated reduction of the azide
to the corresponding aniline. The copper species then coordinates
to aniline, transmetallates with the aryl boronic acid, and finally
undergoes reductive elimination to give the corresponding diaryl
amine (eq 133).
OH
N3
In(0), Cu(OAc)2
+ B
HO
MeOH, 70 ºC, 3 h
80%
H Ph
N HO
Minehan and Papoian have shown that arylindium reagents can
be directly prepared from indium metal and aryl iodides.137 In
the presence of lithium chloride [CAS 7447-41-8], this reaction
proceeds smoothly to generate the organoindium reagent capable
of participating in the palladium-catalyzed cross-coupling reac-
tion. This reaction produces the biaryl products efficiently, even
in the presence of protic solvents. Indium can be regenerated by
the reduction of the residual indium salts via zinc (eq 134).
H 3C
In(0), LiCl
MeO2C I 8. Li, C. J.; Chan, T. H., Tetrahedron Lett. 1991, 32, 7017.
DMF, 80 ºC, 12 h 5 mol % Cl2Pd(dppl)
60 ºC, 2 h
75%
MeO2C CH3
Soengas and Estevez have reported a new method of syn-
thesizing 2-nitroalkan-1-ol using indium from isobutyraldehyde
[CAS 78-84-2] and 1-bromo-1-nitro ethane.138 This reaction gives
a mixture of syn:anti diastereomers in 78% yield and 24:76 ratio,
respectively. Most of the aldehydes used in this study favor the
formation of the anti-isomers over the syn-isomers. The authors
reason that the diastereoselective formation of the anti-isomer can
be explained through a more stable pseudo-chair transition state
(eq 135).
O NO2
+
H Br CH3 THF
78%
24:76 syn:anti
(132)
OH
NO2 (135)
CH3
Hammond and coworkers have reported a new method
for generating gem-difluorohomopropargyl alcohols in aqueous
media.139 This reaction uses catalytic amounts of indium and a
more inexpensive metal, such as zinc, as the stoichiometric reduc-
tant to regenerate indium. With zinc alone, this reaction mainly
affords the propargyl dimeric by-product. Other metals such as
magnesium, aluminum, copper, iron, and tin are not as effective
as zinc in the regeneration of indium metal. The yields are mod-
erate, but the products are formed with high regioselectivity. The
undesired fluoroallenyl alcohols were not detected (eq 136).
In(0) (0.1 equiv),
F O Zn (0.9 equiv) I2
TES F +
Ph H THF:H2O (4:1, 0.3 M),
Br
40 ºC 12 h
66%
F
TES F (136)
(133)
1. Araki, S.; Ito, H.; Butsugan, Y., J. Org. Chem. 1988, 53, 1833.
2. Chao, L.-C.; Rieke, R. D., J. Org. Chem. 1975, 40, 2253.
3. Gynane, M. J. S.; Worrall, I. J., J. Organomet. Chem. 1974, 81, 329.
4. Araki, S.; Ito, H.; Katsumura, N.; Butsugan, Y., J. Organomet. Chem.
1989, 369, 291.
5. Araki, S.; Katsumura, N.; Ito, H.; Butsugan, Y., Tetrahedron Lett. 1989,
30, 1581.
6. Araki, S.; Katsumura, N.; Butsugan, Y., J. Organomet. Chem. 1991,
415, 7.
I 7. Beuchet, P.; LeMarrec, N.; Mosset, P., Tetrahedron Lett. 1992, 33, 5959.
9. Gree, D.; Gree, R.; Lowinger, T. B.; Martelli, J.; Negri, J. T.; Paquette,
L. A., J. Am. Chem. Soc. 1992, 114, 8841.
10. (a) Podlech, J.; Maier, T. C., Synthesis 2003, 5, 633. (b) Cintas, P.,
Synlett 1995, 1087. (c) Li, C.-J., Chem. Rev. 1993, 93, 2023. (d) Li,
C.-J., Tetrahedron 1996, 52, 5643. (d) Li, C.-J.; Chan, T.-H.,
(134)
Tetrahedron 1999, 55, 11149. (e) Paquette, L. A., In Green Chemistry:
Frontiers in Benign Chemical Synthesis and Processing; Anastas, P.,
Williamson, T., Eds.; Oxford University Press: New York, 1998.
11. (a) Loh, T.-P.; Li, X.-R., Angew. Chem. 1997, 109, 1029; Angew. Chem.,
Int. Ed. Engl. 1997, 36, No. 9, 980. (b) Loh, T. P.; Li, X. R., Tetrahedron
Lett. 1996, 38, 869.
12. Woo, S.; Squires, N.; Fallis, A. G., Org. Lett. 1999, 1, 575.
13. Loh, T.-P; Li, X.-R., J. Chem. Soc., Chem. Commun. 1996, 1929.
14. (a) Chan, T. H.; Yang, Y., J. Am. Chem. Soc. 1999, 121, 3229. (b) Gao,
J.; Harter, R.; Gordon, D. M.; Whitesides, G. M., J. Org. Chem. 1994,
59, 3714. (c) Araki, S.; Ito, H.; Butsugan, Y., J. Org. Chem. 1988, 53,
1831.
 INDIUM 21

15. (a) Issac, M. B.; Chan, T.-H., Tetrahedron Lett. 1995, 36, 8957. (b) 42. (a) Li, C. J.; Chen, D. L.; Lu, Y. Q.; Haberman, J. X.; Mague, J. T.,
Hirashita, T.; Yamamura, H.; Kawai, M.; Araki, S., Chem. Commun. J. Am. Chem. Soc. 1996, 118, 4216. (b) Li, C. J.; Chen, D. L.; Lu, Y.
2001, 387. Q.; Haberman, J. X.; Mague, J. T., Tetrahedron 1998, 54, 2347. (c) Li,
16. (a) Loh, T.-P.; Tan, K.-T.; Yang, J.-Y.; Xiang, C.-L., Tetrahedron Lett. C.-J.; Chen, D.-L., Synlett 1999, 737.
2001, 42, 8701. (b) Loh, T.-P.; Tan, K.-T.; Hu, Q.-Y., Tetrahedron Lett. 43. Nair, V.; Ros, S.; Jayan, C. N.; Pillai, B. S., Tetrahedron 2004, 60, 1959.
2001, 42, 8705. (c) Loh, T.-P.; Tan, K.-T.; Chng, S.-S.; Cheng, H.-S., 44. Li, C. J.; Chan, T. H., Tetrahedron 1999, 55, 11149.
J. Am. Chem. Soc. 2003, 125, 2958.
45. Chan, T. H.; Lee, M. C., J. Org. Chem. 1995, 60, 4228.
17. (a) Paquette, L. A.; Stephanian, M.; Mallavadhani, U. V.; Cutarelli, T. 46. Reetz, M. T.; Haning, H., J. Organomet. Chem. 1997, 541, 117.
D.; Lowinger, T. B.; Klemeyer, H. J., J. Org. Chem. 1996, 61, 7492.
47. Shin, J. A.; Cha, J. H.; Pae, A. N.; Choi, K. I.; Koh, H. Y.; Kang, H. Y.;
(b) Lee, P. H.; Anh, H.; Lee, K.; Sung, S.-y.; Kim, S., Tetrahedron Lett.
Chao, Y. S., Tetrahedron Lett. 2001, 42, 5489.
2001, 42, 37.
48. Paquette, L. A.; Rothhaar, R. R.; Isaac, M.; Rogers, L. M.; Rogers, R.
18. Lee, P.-H.; Ahn, H.; Lee, K.; Sung, S.-Y.; Kim, S., Tetrahedron Lett.
D., J. Org. Chem. 1998, 63, 5463.
2001, 42, 37.
49. Kim, E.; Gordon, D. M.; Schmid, W.; Whitesides, G. M., J. Org. Chem.
19. Iwasawa, N.; Miura, T.; Kiyota, K.; Kusama, H.; Lee, K.; Lee, P. H.,
1993, 58, 5500.
Org. Lett. 2002, 4, 4463.
50. Prenner, R. H.; Binder, W. H.; Schmid, W., Liebigs Ann. Chem. 1994,
20. (a) Paquette, L. A.; Mitzel, T. M., Tetrahedron Lett. 1995, 36, 6863. (b)
73.
Paquette, L. A.; Lobben, P. C., J. Am. Chem. Soc. 1996, 118, 1917. (c)
Paquette, L. A.; Mitzel, T. M., J. Am. Chem. Soc. 1996, 118, 1931. (d) 51. Bryan, V. J.; Chan, T. H., Tetrahedron Lett. 1997, 38, 6493.
Paquette, L. A.; Mitzel, T. M.; Isaac, M. B.; Crasto, C. F.; Schomer, W. 52. Kumar, H. M. S.; Anjaneyulu, S.; Reddy, E. J.; Yadav, J. S., Tetrahedron
W., J. Org. Chem. 1997, 62, 4293. Lett. 2000, 41, 9311.
21. Loh, T.-P.; Hu, Q.-Y.; Vittal, J. J., Synlett 2000, 523. 53. Bernardi, L.; Cerè, V.; Femoni, C.; Pollicino, S.; Ricci, A., J. Org.
22. Wang, R.; Lim, C.-M.; Tan, C.-L.; Lim, B.-K.; Sim, K.-Y.; Loh, T.-P., Chem. 2003, 68, 3348.
Tetrahedron: Asymmetry 1995, 6, 1825. 54. Fujiwara, N.; Yamamoto, Y., J. Org. Chem. 1999, 64, 4095.
23. Diana Ho, S.-C.; Sim, K.-Y.; Loh, T.-P., Synlett 1996, 263. 55. Hilt, G.; Smolko, K. I.; Waloch, C., Tetrahedron Lett. 2002, 43, 1437.
24. (a) Loh, T.-P.; Zheng, Y.; Song, H.-Y.; Tan, K.-L., Tetrahedron Lett. 56. Prajapati, D.; Laskar, D. D.; Gogoi, B. J.; Devi, G., Tetrahedron Lett.
2003, 44, 911. (b) Loh, T.-P.; Song, H.-Y., Synlett 2003, 12, 2119. 2003, 44, 6755.
(c) Loh, T. P.; Cao, G. Q.; Pei, J., Tetrahedron Lett. 1998, 39, 1453. 57. Auge, J.; Lubin-Germain, N.; Seghrouchni, L., Tetrahedron Lett. 2002,
(d) Loh, T.-P.; Song, H.-Y.; Zheng, Y., Tetrahedron Lett. 2003, 44, 911. 43, 5255.
(e) Paquette, L. A.; Bennett, G. D.; Isaac, M. B.; Chhatriwalla, A., 58. Araki, S.; Ito, H.; Butsugan, Y., Synth. Commun. 1988, 18, 453.
J. Org. Chem. 1998, 63, 1836.
59. Johar, P. S.; Araki, S.; Butsugan, Y., J. Chem. Soc., Perkin Trans. 1
25. Loh, T.-P.; Lye, P.-L., Tetrahedron Lett. 2001, 42, 3511. 1992, 711.
26. (a) Loh, T.-P.; Zhou, J.-R.; Li, X.-R., Tetrahedron Lett. 1999, 40, 9333. 60. Yoo, B. W.; Hwang, S. K.; Kim, D. Y.; Choi, J. W.; Ko, J. J.; Choi, K.
(b) Loh, T.-P.; Zhou, J.-R.; Yin, Z., Org. Lett. 1999, 1, 1855. I.; Kim, J. H., Tetrahedron Lett. 2002, 43, 4813.
27. (a) Loh, T.-P.; Zhou, J.-R., Tetrahedron Lett. 2000, 41, 5261. (b) Loh, 61. Médebielle, M.; Onomura, O.; Keirouz, R.; Okada, E.; Yano, H.;
T.-P.; Zhou, J.-R.; Li, X.-R., Tetrahedron Lett. 1999, 40, 9115. Terauchi, T., Synthesis 2002, 2601.
28. (a) Huang, J.-M.; Xu, K.-C.; Loh, T.-P., Synthesis 2003, 5, 755. (b) Loh, 62. Pitts, M. R.; Harrison, J. R.; Moody, C. J., J. Chem. Soc., Perkin
T.-P.; Huang, J.-M.; Xu, K.-C., Tetrahedron Lett. 2000, 41, 6511. Trans. 1 2001, 955.
29. (a) Ho, D. S. C.; Xu, K.-C.; Sim, K.-Y.; Loh, T.-P., Tetrahedron Lett. 63. Moody, C. J.; Pitts, M. R., Synlett 1998, 1028.
1996, 38, 865. (b) Loh, T.-P.; Lye, P.-L.; Wang, R.-B.; Sim, K.-Y., 64. Hutchinson, I.; Stevens, M. F. G.; Westwell, A. D., Tetrahedron Lett.
Tetrahedron Lett. 2000, 41, 7779. 2000, 41, 425.
30. Araki, S.; Nakano, H.; Suburaj, K.; Hirashita, T.; Shibutani, K.; 65. Banik, B. K.; Suhendra, M.; Banik, I.; Becker, F. F., Synth. Commun.
Yamamura, H.; Kawai, M.; Butsugan, Y., Tetrahedron Lett. 1998, 39, 2000, 30, 3745.
6327.
66. Yadav, J. S.; Reddy, B. V. S.; Srinivas, R.; Ramlingam, T., Synlett 2000,
31. (a) Araki, S.; Imai, A.; Shimizu, K.; Yamada, M.; Mori, A.; Butsugan, 1447.
Y., J. Org. Chem. 1995, 60, 1841. (b) Ranu, B. C.; Majee, A., Chem. 67. Chen, L.; Li, Z.; Li, C. J., Synlett 2003, 732.
Commun. 1997, 1225. (c) Klaps, E.; Schmid, W., J. Org. Chem. 1999,
68. Kim, B. H.; Jin, Y.; Jun, Y. M.; Han, R.; Baik, W.; Lee, B. M.,
64, 7537.
Tetrahedron Lett. 2000, 41, 2137.
32. Araki, S.; Usui, H.; Kato, M.; Butsugan, Y., J. Am. Chem. Soc. 1996,
69. Moody, C. J.; Pitts, M. R., Synlett 1999, 1575.
118, 4699.
70. Mineno, T.; Choi, S. R.; Avery, M. A., Synlett 2002, 883.
33. Banik, B. K.; Ghatak, A.; Becker, F. F., J. Chem. Soc., Perkin Trans. 1
2000, 2179. 71. Yadav, J. S.; Reddy, B. V. S.; Reddy, K. S.; Reddy, K. B., Tetrahedron
Lett. 2002, 43, 1549.
34. (a) Isaac, M. B.; Chan, T.-H., Pure Appl. Chem. 1996, 68, 919. (b) Isaac,
M. B.; Chan, T.-H., J. Chem. Soc., Chem. Commun. 1995, 1003. 72. Reddy, G. V.; Rao, G. V.; Iyengar, D. S., Tetrahedron Lett. 1999, 40,
3937.
35. Wang, Z.; Hammond, G. B., J. Org. Chem. 2000, 65, 6547.
73. Harrison, J. R.; Moody, C. J.; Pitts, M. R., Synlett 2000, 1601.
36. Lu, W.; Ma, J.; Yang, Y.; Chan, T.-H., Org. Lett. 2000, 2, 3469.
74. Yadav, J. S.; Subba Reddy, B. V.; Kumar Reddy, G. S. K., New J. Chem.
37. Miao, W.; Chan, T.-H., Synthesis 2003, 5, 785. 2000, 24, 571.
38. Lee, P. H.; Bang, K.; Lee, K.; Lee, C.-H.; Chang, S., Tetrahedron Lett. 75. Kim, B. H.; Han, R.; Piao, F.; Jun, Y. M.; Baik, W.; Lee, B. M.,
2000, 41, 7521. Tetrahedron Lett. 2003, 44, 77.
39. Fujiwara, N.; Yamamoto, Y., J. Org. Chem. 1999, 64, 4095. 76. Kamal, A.; Reddy, G. S. K.; Reddy, K. L., Tetrahedron Lett. 2001, 42,
40. Araki, S.; Butsugan, Y., J. Chem. Soc., Chem. Commun. 1989, 1286. 6969.
41. (a) Bryan, V. J.; Chan, T.-H., Tetrahedron Lett. 1996, 37, 5341. (b) 77. Yadav, J. S.; Subba Reddy, B. V.; Muralidhar Reddy, M., Tetrahedron
Paquette, L. A.; Mendez-Andino, J., Tetrahedron Lett. 1999, 40, 4301. Lett. 2000, 41, 2663.
22 INDIUM

78. Cicchi, S.; Bonanni, M.; Cardona, F.; Revuelta, J.; Goti, A., Org. Lett. 111. Kim, S. H.; Lee, S.; Kim, S. H.; Lim, J. W.; Kim, J. N., Tetrahedron
2003, 5, 1773. Lett. 2012, 53, 4979.
79. Cho, S.; Kang, S.; Keum, G.; Kang, S. B.; Han, S. Y.; Kim, Y., J. Org. 112. Moral, J. A.; Moon, S.; Rodriguez-Torres, S.; Minehan, T. G., Org. Lett.
Chem. 2003, 68, 180. 2009, 11, 3734.
80. Moody, C. J.; Pitts, M. R., Synlett 1998, 1029. 113. Aslam, N. B.; Rajkumar, V.; Reddy, C.; Yasuda, M.; Baba, A.; Babu,
81. Lim, H. J.; Keum, G.; Kang, S. B.; Chung, B. Y.; Kim, Y., Tetrahedron S. A., Eur. J. Org. Chem. 2012, 4395.
Lett. 1998, 39, 4367. 114. Aslam, N. B.; Babu, S. A.; Sudha, A. J.; Yasuda, M.; Baba, A.,
82. Kalayanam, N.; Rao, G. V., Tetrahedron Lett. 1993, 34, 1647. Tetrahedron 2013, 69, 6598.
83. Baek, H. S.; Lee, S. J.; Yoo, B. W.; Ko, J. J.; Kim, S. H.; Kim, J. H., 115. Kim, S. H.; Kim, S. H.; Kim, T. H.; Kim, J. N., Tetrahedron Lett. 2010,
Tetrahedron Lett. 2000, 41, 8097. 51, 2744.
84. Ranu, B. C.; Dutta, P.; Sarkar, A., Tetrahedron Lett. 1998, 39, 9557. 116. (a) Kim, Y. M.; Kim, S. H.; Kim, K. H.; Kim, J. N., Tetrahedron Lett.
85. Ranu, B. C.; Dutta, P.; Sarkar, A., J. Chem. Soc., Perkin Trans. 1 1999, 2010, 51, 5922. (b) Kim, S. H.; Kim, S. H.; Lee, K. Y.; Kim, J. N.,
1139. Tetrahedron Lett. 2009, 50, 5744. (c) Kim, S. H.; Kim, S. H.; Kim, K.
H.; Kim, J. N., Tetrahedron Lett. 2010, 51, 860. (d) Kim, Y. M.; Kim,
86. Araki, S.; Butsugan, Y., Bull. Chem. Soc. Jpn. 1991, 64, 727.
K. H.; Park, S.; Kim, J. N., Tetrahedron Lett. 2011, 52, 1378.
87. Chan, T. H.; Li, C. J.; Lee, M. C.; Wei, Z. Y., Can. J. Chem. 1994, 72,
117. Wang, R.; Tian, P.; Lin, G., Chin. J. Chem. 2013, 31, 40.
1181.
118. Auge, J.; Lubin-Germain, N.; Marque, S.; Seghrouchni, L., J.
88. Miyabe, H.; Ueda, M.; Nishimura, A.; Naito, T., Org. Lett. 2002, 4,
Organomet. Chem. 2003, 679, 79.
131.
119. Schneider, U.; Ueno, M.; Kobayashi, S., J. Am. Chem. Soc. 2008, 130,
89. Ueda, M.; Miyabe, H.; Nishimura, A.; Miyata, O.; Takemoto, Y.; Naito,
13824.
T., Org. Lett. 2003, 5, 3835.
120. Heddad, T.; Hirayama, L. C.; Buckley, J.; Singaram, B., J. Org. Chem.
90. Yanada, R.; Koh, Y.; Nishimori, N.; Matsumura, A.; Obika, S.; Mitsuya,
2012, 77, 889.
H.; Fujii, N.; Takemoto, Y., J. Org. Chem. 2004, 69, 2417.
121. Hirayama, L.; Dunham, K. K.; Singaram, B., Tetrahedron Lett. 2006,
91. Capps, S. M.; Clarke, T. P.; Charmant, J. P. H.; Höppe, H. A. F.; Lloyd-
47, 5173.
Jones, G. C.; Murray, M.; Peakman, T. M.; Stentiford, R. A.; Walsh, K.
E.; Worthington, P. A., Eur. J. Org. Chem. 2000, 963. 122. Lee, P. H.; Kim, H.; Lee, K.; Seomoon, D.; Kim, S.; Kim, H. K.; Kim,
K. H.; Lee, M.; Shim, E.; Lee, S.; Kim, M.; Han, M.; Noh, K.; Sridhar,
92. Lee, P. H.; Sung, S.; Lee, K., Org. Lett. 2001, 3, 3201.
M., Bull. Korean Chem. Soc. 2004, 25, 1687.
93. Lee, K.; Lee, J.; Lee, P. H., J. Org. Chem. 2002, 67, 8265.
123. Lubin- Germain, N.; Baltaze, J. P.; Coste, A.; Hallonet, A.; Laureano,
94. Pérez, I.; Sestlo, J. P.; Sarandeses, L. A., J. Am. Chem. Soc. 2001, 123, H.; Legrave, G.; Auge, J.; Uziel, J., Org. Lett. 2008, 10, 725.
4155. 124. Sugi, M.; Sakuma, D.; Togo, H., J. Org. Chem. 2003, 68, 7629.
95. Takami, K.; Yorimitsu, H.; Shinokubo, H.; Matsubara, S.; Oshima, K., 125. Lee, P. H.; Kim, S.; Lee, K.; Seomoon, D.; Kim, H.; Lee, S.; Kim, M.;
Org. Lett. 2001, 3, 1997. Han, M.; Noh, K.; Livinghouse, T., Org. Lett. 2004, 6, 4825.
96. Araki, S.; Butsugan, Y., J. Chem. Soc., Chem. Commun. 1989, 1286. 126. Goeta, A.; Salter, M. M.; Shah, H., Tetrahedron 2006, 62, 3582.
97. Engstrom, G.; Morelli, M.; Palomo, C.; Mitzel, T., Tetrahedron Lett. 127. Shanthi, G.; Perumal, R. T., Synlett 2008, 18, 2791.
1999, 40, 5967.
128. Kim, J. S.; Han, J. H.; Lee, J. J., Jun, Y. M.; Lee, B. M., Kim, B. H.,
98. Banik, B. K.; Ghatak, A.; Becker, F. F., J. Chem. Soc., Perkin Trans. 1 Tetrahedron Lett. 2008, 49, 3733.
2000, 2179.
129. Kim, S. H.; Lee, H. S.; Kim, K. H.; Kim, J. N., Tetrahedron Lett. 2009,
99. Wang, L.; Zhang, Y., J. Chem. Res. (S) 1998, 588. 50, 1696.
100. Zhan, Z.; Zhang, Y.; Ma, Z., J. Chem. Res. (S) 1998, 130. 130. Yadav, J. S.; Subba Reddy, B. V.; Yadav, N. N.; Singh, A. P.; Choudhary,
101. Bao, W.; Zhang, Y., Synlett 1996, 1187. M.; Kunwar, A., Tetrahedron Lett. 2008, 49, 6090.
102. Wang, L.; Sun, X.; Zhang, Y., Synth. Commun. 1998, 28, 3263. 131. Munbunjong, W.; Lee, E. H.; Ngernmaneerat, P.; Kim, S. J.; Singh, G.;
103. Lim, H. J.; Keum, G.; Kang, S. B.; Kim, Y.; Chung, B. Y., Tetrahedron Chavasiri, W.; Jang, D. O., Tetrahedron 2009, 65, 2467.
Lett. 1999, 40, 1547. 132. Marin, G.; Braga, A. L.; Rosa, A. S.; Galetto, F. Z.; Burrow, R. A.;
104. Hirayama, L.; Gamsey, S.; Knueppel, D.; Steiner, D.; DeLaTorre, K.; Gallardo, H.; Paixao, M. W., Tetrahedron 2009, 65, 4614.
Singaram, B., Tetrahedron Lett. 2005, 46, 2316. 133. Shen, Z.; Yeo, Y.; Loh. T., J. Org. Chem. 2008, 73, 3922.
105. Heddad, T.; Hirayama, L. C.; Buckley, J.; Singaram, B., J. Org. Chem. 134. Mahesh, M.; Murphy, J. A.; Wessel, H. P., J. Org. Chem. 2005, 70,
2012, 77, 889. 4118.
106. Dudding, T.; Mirabdolbaghi, R., Org. Lett. 2012, 14, 3748. 135. Lin, M.; Tsai, W.; Lin, L.; Hung, S.; Chuang, T.; Su, Y., J. Org. Chem.
107. Hirayama, L.; Haddad, T. D.; Oliver, A. G.; Singaram, B., J. Org. Chem. 2011, 76, 8518.
2012, 77, 4342. 136. Subba Reddy, B. V.; Sivasankar Reddy, N.; Jayasudhan Reddy, Y.;
108. Du, Z.; Li, Y.; Wang, F.; Zhou, W.; Wang, J., Tetrahedron Lett. 2010, Vikram Reddy, Y., Tetrahedron Lett. 2011, 52, 2547.
51, 1745. 137. Papoian, V.; Minehan, T., J. Org. Chem. 2008, 73, 7376.
109. Han, R.; Choi, S. H.; Son, K. I.; Jun, Y. M.; Lee, B. M.; Kim, B. H., 138. Soengas, R. G.; Estevez, A. M., Tetrahedron Lett. 2012, 53, 570.
Synth. Commun. 2005, 25, 1725. 139. Arimitsu, S.; Jacobsen, J. M.; Hammond, G. B., Tetrahedron Lett. 2007,
110. Chung, W. J.; Higashiya, S.; Oba, Y.; Welch, J. T., Tetrahedron 2003, 48, 1625.
59, 10031.