Literature seminar

S. Majima (M1)
2010/10/06

Indium Chemistry ~ f rom Dr. Baba's works ~Akio Baba was born in Kochi, Japan, in 1949. He received his B.S.
(1971) and Ph.D. degrees (1976) from Osaka University under theguidance of Professor Toshio Agawa. He worked for Mitsubishi KaseiIndustries (now Mitsubishi Chemicals, Inc.) from 1976 to 1981. Hebecame an Assistant Professor at Osaka University in 1981 andAssociate Professor in 1987, working with Professor Haruo Matsuda.
He became Full Professor in 1995. He is now also working as one ofthe project leaders at the Handai Frontier Research Center.
Baba et al. T he Chemical Record. 2005, 5, 323.
Contents
0. Introduction
0-1. What is indium?
0-2. Primary reactions
1. Alkyl indium
1-1. Cyclopropylmethylenylation
1-2. Diene utilized alkylation
2. Indium as a Lewis acid
2-1. Deoxygenative functionalization
2-2. Coupling reaction with silyl enolates
3. C=C or C C bond activation
3-1. C C bond activation
3-2. C=C bond activation
4. Summary

0. Introduction
0-1. W hat is indium?
Cintas, SY NLETT , 1995, 1087.
Reddy et al. Eur. J. Chem. 2010, 591.
121314BC

Recyclable

Easy handling

Stable to air, moisture

AlSiZn Ga Ge

Low toxicity

IndiumLower heterophilicity

Low 1st ionization potencial (5.8 eV)Soft Lewis acid

Good for SET

Cd In Sn
Hg Tl Pbcf) Zn (9.4 eV), Sn (7.3 eV),Mg (7.6 eV), Na (5.0 eV)Indium has these good points. But the prices of indium species is not cheap.
cf) In(OH)3: 12900 Yen/10g, Wako.
InCl3: 13300 Yen/10g, Ald.
InBr3: 17400 Yen/10g, Ald.
In(OTf)3: 14900 Yen/5g, Ald.
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0-2. Primar y r eactions
Gynane et al. J. Org. Chem. 1972, 40, C9.

Gynane et al. J. Org. Chem. 1972, 43, 257.

Butsugan et al., JOC., 1988, 53, 1831.

Marshal et al. JOC. 1995, 60, 1920.
1 eq.
acetone,-78 to rt.
98%

anti:syn = 98:2

Baba et al. T L. 1995, 36, 9497.

acetonitrile

Baba et al. SY NLETT , 1997, 699.

Baba et al. TL, 1998, 39, 1929.

Reduction of ketones, aldehydes, haloalkanes.

21. Alkyl indium
1-1. Cyclopropylmethylenylation
Cyclopropylmethylenylation of -iodoketones(1 eq.)

Baba et al. Organometallics, 2009, 28, 132.

(1 eq.)

Which indium is the active species?

41 eq. InBr3 was not effective.
-> The active species is dibutenylindium 5.

Two alkyl indium species were observed.

Galvinoxyl (radical scavenger) inhibited the reaction.
-> This reaction is radicalic.

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Cyclopropylmethylenylation of alkylchloride

Baba et al. Org. Lett. 2010, 12, 1520.

(5 mol%)(1 eq.)(1 eq.)

Also two species were observed.

Galvinoxyl did not inhibit the reaction.
->This reation is not radicalic; ionic.
Author said this is the 1st report about ionicreaction of organic halides with organoindium.
t-Bu

This structure is differ from the structure in page 3.

t-Bu

OO
t-Bu

t-Bu

Galvinoxyl41-2. Diene utilized alkylation
Alkylation of ketones / imene
Baba et al. Org. Lett. 2006, 8, 4553.

(4 eq.)(2 eq.)(1 eq.)PhCHO

When TEMPO was added before diene, onlyreduction of aldehyde was observed.
In contrast, when TEMPO was added after diene,
alkylation proceeded.
-> Generation of alkylindium is radicalic path, andalkylation step is ionic path.

OH9PhHO10PhNHPh11Ph

Regioselectivity

Plausible mechanism

Baba et al. SYNLET T, 2008, 1407.
e andin situ:()Baba et al. TL, 1998, 39, 1929.
Baba et al. TL, 2001, 42, 4661.
Baba et al. Org. Lett. 2006, 8, 4553.
Other method preparing HInCl2:

Baba et al. Org. Lett. 2004, 6, 4981.
NaBH4

NaCl + BH3

Baba et al. JACS. 2002, 124, 906.
DIBAL

Al(iBu)2Cl

Oshima et al. Org. Lett. 2002, 4, 2993.

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kineticAuthor proposed cyclic TS.
But according to the results of Table 3
in page 3, I think cyclic TS and acyclic
TS are competitive.
thermodynamic

The additive effect is not clear. Does quenching indium alchoxide of C prevent the retroreaction?
When author tried the reaction of acetophenone with 1a in the presence of Ph3P or HMPA, onlya small amount of -adduct was obtained at r.t.. See Entry 5 of Table 2. In absence of Lewis base,only -adduct was observed at r.t..

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2. Indium as a Lewis acid
2-1. Deoxygenative functionalization
Reduction of aryl ketones
Baba et al. SYNLETT , 1999, 182.
R = alkyl, haloalkyl, phenyl
Ar = phenyl, p-MeO phenyl, p-Cl phenyl, naphthanyl

Deoxygenative arylation of ketones
Baba et al. T etrahedron, 1999, 55, 1017.

Deoxygenative allylation of aryl ketones
Baba et al. T L, 2000, 41, 2425.

Plausible mechanisum
I think this intermediate is active species.
(See next page.)
The combinaton of InCl3 and chlorosilane show high Lewis acidity. Baba et al. also achieved catalytic
Sakurai-Hosomi reaction using InCl3-Me3SiCl. cf) Eur. J. Org. Chem. 2002. 1578., Tetrahedron. 2002, 58, 8227.
And catalytic Mukaiyama aldol reaction was reported. cf) Mukaiyama et al. Chem. Lett. 1991. 20. 949.
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Deoxygenative allylation of alcohols
Baba et al. ACIE. 2004, 43, 1414.
R1R2InCl3 (5 mol%)

SiMe2Cl+OH(1 eq.)

R1

R2

CH2Cl2r.t.

(2 eq.)

80 °C

First estimated mechanismcf) Baba et al. JOC. 2001, 66, 7741.

R2OH

R-HClRR

InCl3Cl3InO

R

Si

But in a case of R1=R2=Ph, HCl and intermediate
were not observed on NMR .
And also the reaction was proceeded in the cases ofusing trimethylsilyl.
Baba et al. Synlett. 2005, 11, 1737.

Lewis acidity of trimethylsilylhalides
Me3SiCl<Me3SiBr<Me3SiI

Baba et al. Chem. Commun. 2008, 6396.

Similar mechanism?

R1Same mechanism?

SiMe2Cl

Indium has lower oxophilicity than Al, B etc.
So this process proceeds smoothly.

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Deoxgenative halogenation of ketones
Baba et al. JACS, 2002, 124, 13690.
In(OH)3 (5 mol%),
HSiMe2Cl

O
R1

R2

Cl
R1

R2

I think this is active species.

Iodination

Chloroallylation-> Silyl ether is intermediate.

Deoxgenative chlorination of alchols
Baba et al. JACS. 2004, 126, 7186.
InCl3 (5 mol%),
HSiMe2Cl, additive
R-OHr.t.

R-Cl

additive

But according to this result, I propose other mechanisum.
MeO

9Reactivity: tertiary > secondary > primary (NR.)

MeSiClMeO

MeSiClCl InCl3-InCl3,-(Me2SiO)nDoes benzil play some role?

92-2. Coupling reaction with silyl enol ethers
Baba et al. Org. Lett. 2007, 9, 4931.
Baba et al. T etrahedron. 2009, 65, 5462.

(1 eq.)(1.5 eq.)

slow
First, reaction goes on path A.
Then, TMSCl is generated andreaction is accelerated by path B.
fast

When the amount of 1a or InBr3 was doubled, the reaction
rate was increased.
->The genaration carbocation step is rate-determining step.
When the amount of 2a was increased, the reaction rate
was decreased.
->The coordination of the oxygen atom on the silyl enol ether
deactivates the catalytic activity of InBr3.
This is the reason why the strong Lewis acids showed noactivity.

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3. C=C or C
3.1 C

C bond activation

C bond activation

Baba et al. ACIE. 2009, 48, 4577.

By using Pd catlyst, onepot addition / coupling
reactions were achived.

In some cases, the reactions were proceededby 50 mol% indium catalyst.

[f][f] 2g isomerized to a corresponding -silyl ester.

2 indium species were isolated.

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3.2 C=C bond activation

InF3, InCl3, In(OTf)3 are too hard.
So they are trapped by oxygene atom of keten silyl acetal.

4. Summary• The combination of indium halide and silyl species shows high Lewis acidity.
MeOMeSiCl InCl3

Functionalization• Low oxophilicity of indium enables various reactions.

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