Indium in Organic Synthesis

Huang-Jianzhou2012-04-14

1 、 Introduction1 、 Introduction

2 、 Preparation of Allylindium 2 、 Preparation of Allylindium

3 、 As Lewis Acid3 、 As Lewis Acid

4 、 Cross coupling4 、 Cross coupling

5 、 Reduction 5 、 Reduction

6 、 Conclusion6 、 Conclusion

化合价： 0, +1,+2,+3

1863

5s2 5p1J. Uziel, Synthesis, 2007, 1739.Scott E. Denmark, Chem. Rev. 2003, 103, 2763Basi V. Subba Reddy, Eur. J. Org. Chem. 2010, 591Sujit Roy, Chem. Rev. 2010, 110, 2472Anthony J. Downs, Chem. Rev. 2007, 107, 2

Advantages indium in organic synthsis:

stable in air and waterNotoxicity for manLow first ionization potential, can be an effective single electron transfer agentorganoindium reagents are easy prepared

1 、 Introduction

4

IO OH

+

In, DMF,rt

Yasuo Butsugan, J. Org. Chem., 1988, 53, 1831

PhCHOI

+In, DMF,rt

Ph

OH

89%

87%

PhCHOBr

+In, H2O,80℃

Ph

OH

97%

T. H. Ghan, Tetrahedron Lett. 1991, 32, 7017

In 1988,

In 1991

2In + 2BrCH2CO2Et BrInCH2CO2Et

CH2CO2Et

PhCHOPh

OH

CO2Etxylene

83%

Reuben D. Rieke, J. Org. Chem, 1975 , 40, 2253

Ph Br PhCHO+

Ph

OH

Ph

In, H2O88% yieldanti : syn = 96:4

R2

R1

X In+R2

R1

InR1

R2In

InOR2

R

R1

InO R

R1

R2

R CHO

Tak-Tang Chan, Tetrahedron Lett. 1995, 36, 8957

Regioselectivity

5

6

Br

F FPhCHO+

In, H2O

100%Ph

OH

F F

Feng-Ling Qing, Tetrahedron Lett. 1998, 54, 14198

O

H BrIn, H2O

OH OH

¦Á-adduct ¦Ã-adduct

yield = 85 %(¦Á : ¦Ã = 99 : 1)

Teck-Peng Loh, Tetrahedron Lett. 2001, 42, 8701

O

I In

TMSCl THF

+ +

OO

O

Br

In, THF, 0℃ to rt

OHO

O

Leo A. Paquette, J. Org. Chem. 1996, 61, 7492

O

100%

THFOH

Phil Ho Lee,Tetrahedron Lett, 2001, 42 , 37

or CuI

Diastereoselectivity

8

Cy

OTBS

H

OTBS

H

O

Br In, H2O

OTBS

OH

OTBS

OH+ +

anti : syn = 3.9:1

yield = 90 %

OH

H

O

Br In, H2O+

yield = 85 %

OH

OH

OH

OH+

anti : syn = 1 : 9.8

O

H

InO

H

O

Cy H

In

InO

OHCy

TS-aTS-b

Cram rule

Leo A. Paquette, J. Am. Chem. soc. 1996, 118, 1931

9

In0

X X

H2O org solvInⅠ InⅢ

XInⅢ

X

x

TmⅡ

X

org solv

InⅡ X

TmⅡ

X

H2O

InⅠ Inx

TmⅡ

X InⅢ XInⅠ x

X

InⅢ x3 Mgm *InⅢ X3-n

n

n = 1, 2, 3

2 、 Preparation of Allylindium

Pd0

PdⅡ

X

X

PdⅡ

InX X

InX

InX

X

X

X = OAc, Cl, OPhOCOOEt, OH

+InI, Pd(PPh3)4 Ph

OH43%-100%

Shuki Araki, Org. Lett. 2000, 2 , 847

PhCHO

11

NO

O

Pd0N

Pd

O

COMeInI

N

Pd

O

COMe

In I

Pd0

InO

N

I

COMe

PhCHOIn

NO

HI

R

COMe

In

NO

RI

H

COMe

NR

OHHO

O

NR

OHHO

O

NO

O

PhCHO+Pd(OAc)2, PPh3, InI

THF/H2O

NR

OHHO

O

NR

OHHO

O

Org. Lett., 2009, 11 , 1293

Marvin J. Miller, J. Org. Chem., 2003, 68, 139

PhCHO+

InINi(acac)2(10%mol)

PPh3, THF, rt, 4h

OH

PhPh

OH

Tsunehisa Hirashita, Chem Commun, 2006, 2595

Ph

OH

Ph

OH

Ph

OH

4%

36%

54%

In,Ni(0), H+

In,Ni(0), PhCHO

Ni

H+H

Ni InI H

InL2

PhCHO

1

2

3

1

Ni

O

Ph

InO Ni

In

InI

Ph

OInL2 InL2

Ph

OInL2 InL2

2

3

13

allenesI CHO

MeO

+allene(1 bar)

DMF, In, Pd(PPh3)4

OH

OMe

Ronald Grigg, Chem Commun, 2000, 645

64%

Pd(0) R1X

R1PdX

R2

R2

Pd XR1

R1

PdX

In

R2

R1

Pd

R2

In

R1

InXR2RCHO

R1

R2

OHR

14

NTs

O

PhI+

In(1.2eq), Pd(OAc)2(5mol%)

OP3

10mol%, DMF

N

Ph

OHTs

H

H

N

Ph

OHTs

H

H

cis(80%) trans(13%)

I

O

Pd(PPh3)4

DMF, InO+

O

OH

50%, dr = 1.2:1

I

N

N

O

Ph

+

allene(1 bar)DMF, In, Pd(0)

61% NO

HNPh

Ph

Ronald Grigg, Chem Commun, 2002, 1372

Suk-Ku Kang, J. Org. Chem. 2002, 67, 4376

In

+

X

orgnic solvent(DMF or THF)

ionic liquid

InⅠ InⅢ

In

Me Br I

BrIn

BrIn

BrMe Me

Me

IIn

IIn

I

DMF

InⅠ

H2O

InⅢX

X

Araki, J. Org. Chem. 1988, 53, 1831

Tak Hang, J. Am. Chem. Soc. 1999, 121, 3228 J. Org. Chem. 2007, 72, 923

The reactivity of the allyl halide ： I ≈ Br >> Cl, F inactive

allylindium intermediate

16

OEtBr

OH

PhCHO+In(2eq),H2O, rt OEt

OH

HOPh

95 % (de = 100%)

Yves Canac, J. Org. Chem. 2001, 66, 3206

Leo A. Paquette, J.Org. Chem. 1999, 64, 217

Br O

O

PhCHO+In, H2O/THF

91%syn : anti = 85 :15

Ph

OH

OCOCH3

Br

OOH

PhCHO+

1. In/THF-H2O2. 6N HCl

75 %

OO

Ph

Prabir K. Choudhury, Tetrahedron Lett. 1998, 39, 3581

Shuki Araki, J. Org. Chem. 1999, 64, 172

PhCHOClCl + In, LiI, DMF

83% Ph

OH

Cl

syn : anti = 92:8

Addition to C=O Bonds

NH

O

OBr

In(2eq), THF/H2O(1:1)

0¡æ, 2h NH

OH

O

100%Benito Alcaide, J. Org. Chem. 2005, 70, 3198

Subodh Kumar, Tetrahedron Lett, 2003, 44 , 2101

NH

CHO

Br

NBn

+ +In, THF/H2O(2:1)

30¡æ

NH

NBn

93 % yield

Teck-Peng Loh, Org. Lett., 1999, 1 , 1855

Br + PhCHO

(+)-cinchonine(2eq), In(2eq)THF/n-hexane(3:1)

-78 to 25¡æ,2hPh

OH

73% yield72 % ee

N

NHO

Tetrahedron Lett ,1999, 40, 9333

Tetrahedron Lett, 1999, 40, 9115

Br + PhCHO

ligand(2.6eq), In(10eq)Ce(OTf)4¡¤xH2O

EtOH/H2O(1:1)25¡æ,2h

Ph

OH

90% yield92 % ee

NON N

O

iPrPri

PhCHO + BrIn(2eq), ligand(2eq), py(2eq)

THF/n-hexane, -78¡æ, 1.5h

Ph

OH

99 % yield93% ee

L. C. Hirayama, Tetrahedron Lett , 2005, 46, 2315

NH2

Ph

HO

Ph

Asymmetry

Addition to C=N Bonds

X

In+

Ph

NPh OH

Ph

N

H

PhO

X = Br, DMF-H2O,rt

Ph

NHSO2Ph

H

X = Br, THF, rtPh

NHSO2Ph

90%

88 %

N

H

NOMe

X = Br, H2O, rt

N

HNOMe

EtO2C CN

Ph

X = I, THF, rt

EtO2C

Ph

NH265%

70%

N

ClCO2Ph

N

OPh

O

92%

X = Br, THF,rtPh

N

H

HN

p-tolSO2

X = Br,DMF-H2O, rt

89 %

Ph

NH

HN

p-tolSO2

N

Ph

CH2OH

HN

Ph

CH2OH

71%

X = I, THF, rt

Ph H

NS

O

ONMe2

X = Br,THF, rt

Ph

HNS

O

ONMe2

90%

Ph H

NN

OO

X

3eq

In(0)(2eq), 4A MS,THF, 0 to rt

ligand(10mol %)

+

Ph

HNN

OO

SO2CF3

SO2CF3

OH

OH

X = I, 95%(88% ee)

X = Br, 82%(90% ee)

J. Am. Chem. Soc. 2007, 129, 3846

Ph H

NN

OO

I

3eq

In(0)(2eq), 4A MS,THF, 0 to rt

ligand(X mol %)

+

Ph

HNN

OO CF3

CF3

OH

OH

X = 10 mol %, 77%(70%ee)X = 100mol%, 72%(84%ee)

Org Lett, 2005, 7, 2767

Ph H

NN

OO

I+

i-Pr

In(0)(2eq), 4A MS

THF, 0 to rtPh

HNN

OO

i-Pr

99%(dr > 99;1)

Gregory R. Cook, Org Lett, 2004, 6, 1741

Asymmetry

Ar H

NNHBz

Br+

In(0)(1.5eq)catalyst(10 mol%)

0℃, Ar

HNNHBz CF3

F3C NH

NH

O

HNS O

But

Eric N. Jacobsen, Angew. Chem. Int. Ed. 2007, 46, 1315

Ar = Ph, 87%(91% ee)

Ar = p-ClC6H4, 83%(92 %)

Ar = o-BrC6H4, 78%(93%)

N

O NO H PF6

Ph H

NNHBz

Br+

In(0)(1.5eq)catalyst(10 mol%)

0℃, Ph

HNNHBz

94%(99 % ee)

Doo Ok Jang, J. Am. Chem. Soc. 2010, 132, 12168

Ph H

NNH

PhO

+B(pin)

InI(5mol%), ligand(5mol%)24h,tol/CH3OH, 0℃

Ph

HNNH

PhO

99%(98:2 er)

B(pin)

Me

InI(10mol%), ligand(10mol%)CH2Cl2/CH3CH2OH, 0℃

Ph

HNNH

PhO

Ph

HNNH

PhO

anti synα α

anti : syn = 19:185%,

97:3 er

Ph H

NNH

PhO

+

Shu Kobayashi, Angew. Chem. Int. Ed. 2010, 49, 1838

B(pin)

R

Lewis baseInL LIn

R

CN

O

N HN

OPh

Ph

Ph

Ph

Addition to C-C Multiple Bonds

BuBr+

In, THF, rt Bu

86%Brindaban C. Ranu, Chem Commun, 1997, 1225

HOIn2Br3

3+

100℃, DMFOH

OH+

91% yield

85 : 35Yasuo Butsugan, J. Org. Chem. 1995, 60, 1841

Shuki Araki, J. Am. Chem. Soc. 1996, 118, 4699

OHIn2x3+

DMF, 140℃, 4hOH

44%(100%)

OMe NROH NR

InR4

R5H

O HR1

R2

H

R3

InR4

R5H

O HR1

R2

H

R3

24

Other ways

MgBr InBr3

PhIn

3

CN

CNPh

DMFPh

Ph

CN

CN

yield = 76 %

Shuki Araki, Tetrahedron Lett. 1999, 4, 2331

H

O

SnBu3+

InCl3OH

Meacetone, -78 to rt

90 %yieldanti : syn = 98:2

James A. Marshall, J. Org. Chem. 1995, 60, 1920-1921

PhCHO OAc+InI, Ni(acac)2, PPh3

rt, 1hPh

OH97 % yield

Shuki Araki, J. Org. Chem. 2004, 69, 5054

3 、 As Lewis Acid

O

C8H17

OC2H5

O In(OTf)3(5mol%)3A MS,Acetyene(1atm)

solvent free, 100¡ãC, 36h

O

OC2H5

O

C8H17

25.4g 90%

Org Lett. 2005, 7, 3279

Eiichi Nakamura, J. Am. Chem. Soc. 2003, 125, 13002

O

OC2H5

OPh H+

In(OTf)3(5mol%)

neat, 100-140¡ãC

O

OC2H5

O

Ph99%

J. Am. Chem. Soc. 2008, 130, 4492

OEt

ONHs-Bu

MeO

Ph H+

1)In(OTf)3(10mol%)BuLi(10mol%), 120, 8h

2)aq AcOH/THF

O

OC2H5

O

Ph

92%(94% ee)

J. Org. Chem. 2010, 75, 8322

Veronique Michelet,Org Lett. 2010, 12, 2582

O

H

MeO2C CO2Me

InCl3(20mol%)(Cy)(i-Pr)NH(20mol%)

DCE,80¡ãC

OHCMe

CO2MeCO2Me

82%

N

H

MeO2C CO2Me

InCl3

Cy i-Pr

Coniaene reaction

Eiichi Nakamura, J. Am. Chem. Soc. 2008, 130, 17161

CO2Me

N

PMB

CO2MeO In(OTf)3 (5 mol%), DBU (5 mol%)

toluene, reflux

NO

PMB

CO2MeCO2Me

90%

In(OTf)3

DBU TfOH-DBU

R2

NOR1

OMeO

OIn(OTf)2

MeO

R3

ON

OO

InOTfOTf

R3

R1

R2

MeO

MeO

Susumi Hatakeyama, Angew. Chem. Int. Ed. 2008, 47, 6244

COOMeEtOOC In(OTf)3(10mol %)

60 °C, 24 h, neat

EtOOC COOMe

99%

MeO

O O

+

In(NTf2)3(1mol%) EtO2C

EtO2Ctol, 150

98%

O O

OR2R1

LnIn

Eiichi Nakamura, Org Lett. 2009, 11, 1845

O

MePh

InI3(0.2eq) p-TSA(0.05eq), H2O(0.95)

DCM,rt

OMeO

Ph

O

46 %Proposed Mchanistic Pathway

O

RAr

In

O

In

ArR

H2O

O

ArR

In

OH

OH

ArR

O

H+

OH

ArR

O

ORO

Ar

O

John K. Snyder, Org Lett. 2011, 13, 4280

Aldol, Minnich, D-A Reaction

+ 4Cl-PhNH2

H

H

OTMSInCl3(20%)

H2O

NH

H

O

Teck-Peng Loh, Tetrahedron , 2000, 56, 3227

OMe

TMSOH

O

+1) ligand-In(OTf)3(5mol%)

PhOMe

2) TFAO

O

Ph

Xiaoming Fen, Angew. Chem. Int. Ed. 2008, 47, 1308

96%(98% ee)trans : cis < 1:20

NNO O

NHO

PhPh

OHN

PhPh

Org Lett. 2011, 13, 3668

H

O

HO

O

+

Cl

H

HO

O 63%

Shu Kobayashi, Tetrahedron Lett, 1998, 39 ,1579

PhCHO +OSiMe3 InCl3, rt,neat

10min

OH O

61%

Teck-Peng Loh, J. Am. Chem. Soc. 2008, 130, 16492

EtH

O

O

+

In(OTf)3(5mol%)ligand(6mol%)

4A MS, DCE,rt5d

OH

OEt

O

NON N

OH

H

H

H

96%(95% ee)

Carbonyl-ene Reactions

Ph H CHO NHBn2+ +

InCl3, tol, 120°C

98%

H

O

Ph

InBr3(10mo;%)(R)-Binol(10mol%)

Cy2NMe(50mol%)CH2Cl2,40°C

OH

Ph

95%(98% ee)

Masakatsu Shibasaka, J. Am. Chem. Soc. 2005, 127, 13760

NBn2

Ph

Lei Wang, J. Org. Chem. 2009, 74, 4364

5 、 Cross-Coupling

Teck-Peng Loh, Angew. Chem. Int. Ed. 2011, 50, 511

Luis A. Sarandeses, Org Lett. 1999, 1, 1267

Ph3InX

Me

+Pd(Ph3P)2Cl2

THF, refluxMe

96%

J. Am. Chem. Soc. 2001, 123, 4155

3 3

Ph3In

Ac

X+

Pd(Ph3P)2Cl2

THF, reflux Ac

X = OTf, 95%X = Br, 91%

Paul Knochel, Angew. Chem. Int. Ed. 2009, 48, 2236

Aiwen Lei, J. Am. Chem. Soc. 2008, 130, 9429

Paul Knochel, Angew. Chem. Int. Ed. 2008, 47, 7648

Teck-Peng Loh, J. Am. Chem. Soc. 2010, 132, 15852

Et

O In(0.8eq)/InCl3(0.4eq)

CH3CN/H2O, 82%Et

O In O

Et

Cl

Ph

O

Cl

PdCl2(PPh3)2, THF, reflux, 24hEt

O

Ph

O

83%

2In + InCl3

Umpolung

I

AcPdCl2(PPh3)2, LiClDMA. 100¡ãC, 24h

Ac

O

Org Lett. 2011, 13, 422

3InCl

Akio Baba, Synlett, 1999, 182

J. Org. Chem. 2001, 66, 7741-

Ph Ph

OMe2SiClH +

InCl3(5mol%)

CH2Cl2,25°C Ph Ph

99%

Cl

O

Cl

OH

Ph2SiClH +

77%

InCl3(5mol%)

(CH2Cl)2,80°C

4 、 Reduction

Reductive Aldol Reaction

Akio Baba, Angew. Chem. Int. Ed. 2004, 43, 711

Ph

O

Me

MeO

CHO

+

Et3SiHInBr3(10mol%)

EtCN, 0¡ãC, 4hPh

O OSiEt3

OMe

75%,syn : anti = 90 : 10

InBr3 + Et3SiH

HInBr2

+Et3SiBr

+

OInBr2

Ph CH3

O

InBr3O

H

Ar

H

Ph

Ph

O OInBr2

OMe

Et3SiH

Ph

O OSiEt3

OMe

Ph

O

Me

Akio Baba., Angew. Chem. Int. Ed. 2011, 50, 8623

Ph OH

O

OMe

OSiMe3 InBr3(MeO)3SiH

CH2Cl2,rt Ph

O

OMe

O

90 %

R1 OH

OInBr3HSi(OMe)3

R1 O

OBr3In

H Si(OMe)3H

InBr3, H2

R1 O

O

SiOMe

m n

InBr3

R2

R3

OR4

OSiMe3

InBr3Me3Si(OMe)3

R1

O

R2R3

OR4

O

6 、 Conclusion

Indium and its salts provide various methodologies for formation C-C bond, with high reactivity and the unique selectivity;Work is still ongoing, especially in enantioselective reactions.