ionic liquids in organic synthesis - university of north ... · pdf filewhat is an ionic...

15 November 2006 Ionic Liquids AMA 1

Ionic Liquidsin

Organic Synthesis

Adam M. Azman15 November 2006


What is an Ionic Liquid?• Any salt above its melting point• Technically, all molten salts, such as NaCl

(mp = 800oC), are ionic liquids• Obviously not practical for organic synthesis


What is an Ionic Liquid?• Definitions from Literature

– “The term ionic liquid implies a material that is fluid at (or close to) ambient temperature, is colorless,has a low viscosity and is easiliy handled.” (Sheldon)

– “Room temperature ionic liquids are generally salts of organic cations, e.g. tetraalkylammonium,tetraalkylphosphonium, N-alkylpyridinium, 1,3-dialkylimidazolium and trialkylsulfonium cations.”(Sheldon)

– “Most basic definition of a room temperature ionic liquid is a salt that has a melting point at or nearroom temperature.” (Handy)

– “Organic salts with melting points below ambient or reaction temperature.” (Maio)– “Ionic liquid is a salt with a metling temperature below the boiling point of water.” (Wilkes)

– Salt of organic cation which has amelting point near ambienttemperature (up to ~100oC)H

R

HAl2Cl7

Et3NHCuCl2

PF6

NN

NCl

AlCl3


Synonyms for Ionic Liquids• Ionic Liquid (IL)• Room temperature ionic liquid (RTIL)• Molten salt• Room temperature molten salt• Ambient temperature molten salt/ionic liquid• Task specific ionic liquid (TSIL)• Liquid organic salt• Fused salt• Neoteric solvent


A (very) Brief History of Ionic Liquids• 1800s – So called “red oil” formed during Friedel-Crafts reactions

– Identified as long presumed intermediate called sigma complex• Early 1900s - Alkylammonium nitrates found to be liquids at room

temperature– Ethylammonium nitrate (1914) has melting temperature of 12oC– Used as liquid propellants for naval guns

• 1960s-Present – Air Force Academy has continuous research effort forionic liquds for thermal batteries

– Thermal batteries have molten salt electrolyte (LiCl-KCl)– Reaches temperatures between 375-550oC

• Start of modern era of ionic liquids began with discovery of 1-butylpyridinium chloride-aluminum chloride mixture

– Melting point = 40oC, butylpyridinium cation easily reduced• It was noticed that large anions with many degrees of freedom inhibited

crystalization until lower temperature– Large, asymmetric anions should lower melting point, as should large, asymmetric cations

• 1970s – Fast computer method (1 week) for predicting electrochemicalproperties of ammonium salts

– Imidazolium theorized to be excellent candidate (experimentally true)– Imidazolium cation more stable to reduction, melting point below room temperature

• Chloroaluminate salts are reactive to water – not a problem for batteries– Early 1990s – Ethylmethylimidazolium halides prepared, then anion metathesis with various silver

salts provided a small library of room temperature ionic liquids• Late 1990s-Present (and beyond) – Envelope (as always) being pushed

– Exotic anions, functionalized cations, functionalized anions, chiral cations/anions, …– Limitless possibilities of new ionic salts to fill every niche of chemistry

H

R

H

Al2Cl7-

N Cl-

AlCl3

Wilkes, J. S. Green Chemistry, 2002, 4, 73-80

NNRR


Properties• Non-flammable• Negligible vapor pressure• High thermal/chemical/electrochemical stability• Solvating ability• Large liquidus range (span of temperatures between melting and

boiling point of a liquid)• Easy recyclability• Highly polar• Non-coordinating• Tunable miscibility with water or organic solvents• Generally do not coordinate with metals, enzymes• Able to be stored for long time without decomposition• Chiral ionic liquids may control stereoselectivity

“Pure imidazolium ionic liquids can be described as polymeric hydrogen-bonded supramolecules and in some cases when mixed with othermolecules, they should better be regarded as nonstructured materials withpolar and non polar regions rather than homogeneous solvent.” (Dupont)


Properties• Stability/Thermal decomposition

– Imidazolium cation stable above 300oC– Decomposition: cleavage of C-N bond between imidazole nitrogen and alkyl

chain– Anion plays a role

• Less nucleophilic – higher stability• Density

– Least effected by temperature variation or impurity– All greater than 1 for imidazolium cation– Lengthening alkyl chain – lower density– Increasing halogen content – higher density

• Viscosity– Even least viscous room temperature ionic liquids are quite viscous

compared to conventional solvents– Highly sensitive to temperature and impurities– Short alkyl chain/functionalized alkyl chain – lower viscosity

• Longer alkyl chain – increased van der Waals forces – increased energy requiredfor molecular motion

– BF4- anion causes lower viscosity than PF6

- anion• Conductivity

– Inversely parallels viscosity


The Cation• Infinite in number• Most common:

– Dialkylimidazolium– Alkylpyridinium– Tetraalkylammonium– Tetraalkylphosphonium

• Can be tuned to properties needed• For liquid at room temperature, should be

unsymmetrical– Functionalizing side chain on cation can change melting

point of straight-chain relative– Presence of C2-methyl group generally increases melting

point of unsubstituted relative– Substituting at C4 has little effect on melting point

NNRR

N R

NR

R

RR

PR

R

RR


The Anion• Much diversity

– Common:• Tetrafluoroborate• Hexafluorophosphate• Bis(trifluoromethanesulfonyl)imide• Halogen• Mesylate/tosylate/triflate

• Larger, more weakly coordinating anion– lower melting temperature

B-

F

F

F

F

P-

F

F

FF

F

F

N

FF

FS

OO

FF

FSO

O

O S

O

O

O S

O

O

S

O

O

-O

F

F

F


Melting point for R Methyl Imidazolium Cation with Varying Anion

-100

-50

0

50

100

150

200

250

0 2 4 6 8 10 12 14 16 18 20

Length of Alkyl Chain (# Carbon Atoms)

Me

ltin

g P

oin

t (d

eg

C)

BF4

Br

Cl

Ms

NTf2

PF6

Tf

Melting Point Variation

Melting Points for Symmetrical Ionic Liquids (PF6 Anion)

-100

-80

-60

-40

-20

0

20

40

60

80

100

120

0 1 2 3 4 5 6 7 8 9 10

# Carbon atoms (per side)

Me

ltin

g P

oin

t (d

eg

C)

NNMe

X-R

R methyl imidazolium cation[Rmim][X]

NNR

PF6-

R

symmetrically substitutedimidazolium cation

[RRim][PF6]


Partial Miscibility Chart(R Methyl Imidazolium Cation)


Other Ionic Liquid Cations• Pyridinium

– Possibly unstable in presence of nucleophiles– Alkyl chain length effect on melting point mirrors

imidazolium• Tetraalkylammonium

– Known for much longer than imidazolium– Highly viscous/difficult to handle– Long alkyl chain/decreased symmetry – lower

melting point• Others

– Triazolium, pyrazolium, thiazolium,benzimidazolium

– Guanidinium, phosphonium, sulfonium


“Synthesis”


Why do I care?• “Problems” with molecular solvents:

– Grant money becoming more competitive– Chemical “bunker” a real inconvenience– Toxic/hazardous properties of solvents, notably chlorinated hydrocarbons– Expensive catalysts– Strong acids– High temperatures– Long reaction times– Possible cumbersome isolation procedures– Other drives to anchor catalyst for recovery/reuse require additional

catalyst/enzyme modification• Steric hindrance causes decrease in efficiency of reaction

• “Solutions” with ionic liquids:– Combine best advantages of molten salts and avoid worst disadvantages

caused by high temperatures– Two phase system allows product in one phase, everything else in other

phase– Ionic liquid immobilizes catalyst/reagent for recycling and reuse– Ionic liquids can act as solvent and catalyst in some systems without

need for additional catalyst or ligand– Rate acceleration effect on some catalytic reactions


Limitations• A “dearth” of information on biodegradability and toxicity• Cannot be purified by distillation• Trace impurities can have significant impact on physical properties–

must be initially produced in high purity• Some ionic liquids are prone to hydrolysis – especially in reactions

involving metals• C2 hydrogen relatively acidic (pKa = 21-23)

– Deprotonation generates N-heterocyclic carbene– Good ligand for metal complexes

• Oxidative addition to electron-rich Ni0 or Pd0 to generate(carbene)metal hydride compounds

• Decomposition possible under sonochemical conditions– Creates hot spots in solvent– May limit ultrasound- and microwave-assisted processes


Applications• Storage media for toxic gases• Lubricants• Performance additives in pigments• Propellants• Organic chemistry:

•Hydrogenation•Hydroformylation•Alkoxycarbonylation•Cross coupling (Heck, Suzuki, Negishi, Stille)•Allylic substitution•Friedel-Crafts alkylation•Diels-Alder•Diol/carbonyl protection•Epoxidation/Epoxide opening•Cyanosilyation of aldehydes•Esterification•Ring closing metathesis•Knoevenagel condensation•Baylis-Hillman

•Wittig•Robinson annulation•Dihydroxylation•Alcohol oxidation•Friedlander reaction•Nitration of phenols•Bromination of aromatics/alkynes•Cyclopropanation•Synthesis of 2,4,5-triaryl imidazoles•Synthesis of 3,4-dihydropyrimidin-2(1H)-ones•Dimer-/Oligomer-/Polymerization•Chiral solvent for asymmetric synthesis•Kinetic resolution•Biocatalysis


Diol/Carbonyl Protection

• In molecular solvents – large excess of reagents• Monosubstituted imidazolium ionic liquids serve as Brønsted acids• Acidic ionic liquids afford protected product with:

– No added catalyst– 1:1 ratio of carbonyl to diol– No refluxing/Dean-Stark trap– No molecular solvent– Recyclable catalyst

• Acetals immiscible with ionic liquid – no need to remove water

Wu, H-H.; Yang, F.; Cui, P.; Tang, J.; He, M-Y. Tetrahedron Lett., 2004, 45, 4963-4965.

R1 R2

O

HOR3

OH [Hmim][BF4]90°C

R1 R2

OO

R3NHN Me

BF4-

[Hmim][BF4-]


Diol/Carbonyl ProtectionR1 R2

O

HOR3

OH [Hm im ][BF4]90°C

R1 R2

OO

R3

Carbony l A lc ohol Molar Ratio Convers ion (%)Selec tivi ty (%)Time (h)

1:1 981003

1:1 1001003.5

1:1 931006

1:1 761006

1:1 931006

1:1 1001006

1:1 971006

1:1 941006

1:192

1003

1:2 1001003

1:2 601006

1:2 1001006

nhex H

O

O

O

O

Ph H

O

H

O

nhex H

O

O

O

O

Ph H

O

H

O

NO 2

NO 2

HO OH

HO OH

HO OH

HO OH

HO OH

HO OH

HOOH

HOOH

HOOH

HOOH

HOOH

HOOH

92 94 94 94

95 94 95 94

NHNBF4

-

[Hm im ][BF4]

Wu, H-H.; Yang, F.; Cui, P.; Tang, J.; He, M-Y. Tetrahedron Lett., 2004, 45, 4963-4965.


Friedlander Synthesis

• Common additives: HCl, H2SO4, PTSA, microwave, ZnCl2/NEt3, ruthenium orpalladium complexes

• Can be run in ionic liquid with no additive• Efficacy correlated to basicity of anions of ionic liquid

• Ionic liquid can be recovered almost completely and recycled at least twice

Ionic Liquid pKa of Acid of Anion, HX Yield (%)

[bbim][ClO4] -11 37

[bbim][Br] -9 50

[bbim][Cl] -7 50

[bbim][PF6] 70

[bbim][BF4] 750.5

[Hbim][ClO4] -11 50

[Hbim][Br] -9 75

[Hbim][Cl] -7 73.8

[Hbim][PF6] 90

[Hbim][BF4] 0.5 96

NN

NHN Bu

BuBu

X-

X-

[bbim][X]

[Hbim][X]

O

R1

NH2

O

R2 R3

N

R1

R2

R3

Palimkar, S. S.; Siddiqui, S. A.; Daniel, T.; Lahoti, R. J.; Srinivasan, K. V.; J. Org. Chem., 2003, 68, 9371-9378.


Friedlander Synthesis

O

H

NH2

Me

O

H

Muchowski, J. M.; Maddox, M. L.; Can. J. Chem., 2004, 82, 461-478.

NH2

H

OOH

H

O

N

O

H

NH

NH

O

H

NN

OH

H

O

N

N

H

O

HN

NO

H

H

H

O

O

H

NH

N

O

H

NN

HAr

O

H

N

H


Friedlander SynthesisO

R1

NH2

O

R2 R3

N

R1

R2

R3

Compound 1 Compound 2 Product Time (h) Yie ld (%)

O

R2

NH2A - R1=H, R2=Me

B - R1=Cl, R2=Ph

Me

O

OE t

O

N

R2

Me

OE t

O

Me

O

Me

O

O

O

O

O

Me

O

Me

MeO

R1

A

B

R1

N

R2

Me

Me

O

R1

N

R2

R1

N

R2

R1

N

R2

R1

N

R2

R1

N

R2

Me

Me

R1

N

R2

Me

R1Ph

394 94 93

3.393 93 91

397 96 95

398 96 96

973

95 95

493 92 91

691 90 90

3.393 93 92

94 93 93

94 94 93

96 95 94

96 96 94

97 96 95

94 94 93

93 92 90

93 93 91

A

B

A

B

A

B

A

B

A

B

A

B

A

B

A

B

A

B

A

B

A

B

A

B

A

B

A

B

[Hbim ][BF4]

[Hbim ][BF4]

NHNBu

BF 4-

Palimkar, S. S.; Siddiqui, S. A.; Daniel, T.; Lahoti, R. J.; Srinivasan, K. V.; J. Org. Chem., 2003, 68, 9371-9378.


Knoevenagel Condensation/Robinson Annulation

• Reactions performed in air without rigorous drying of ionic liquid• Product extracted with toluene• Ionic liquid washed with toluene and reused without further purification

EWGEWG

R

O

H

EWGEWG

R

Morrison, D. W.; Forbes, D. C.; Davis, Jr., J. H. Tetrahedron Lett., 42, 2001, 6053-6055.Forbes, D. C.; Law A. M.; Morrison, D. W. Tetrahedron Lett., 47, 2006, 1699-1703.


Knoevenagel Condensation/Robinson AnnulationEWGEWG

R

O

H

EWGEWG

R

glycine (0.2 eq.)

[hexmim][PF6]22 h, 45-55°C

Car bonylDerivative

Yie ld (%) (unoptim ized)

86

74

77

62

32

Cl H

O

ClH

O

H

O

H

O

O2N

MeO

O

H

EtO

O

Me

OO

48

MalonateDeriv ative

CNNC

CNNC

CNNC

CNNC

CNNC

Cl

Cl

O2N

MeO

CN

CN

CN

CN

CN

CN

CN

CN

CN

CN

OO

EtO

Pr oductNN

Menhex

[hexm im ][PF6]

PF 6-

H2N

O

OH

gly cine

“10 cyclesperformed without

dropping below90% conversion.”

Morrison, D. W.; Forbes, D. C.; Davis, Jr., J. H. Tetrahedron Lett., 42, 2001, 6053-6055.Forbes, D. C.; Law A. M.; Morrison, D. W. Tetrahedron Lett., 47, 2006, 1699-1703.


Hydrogenation• First example by Chauvin, 1995• Dupont showed RuCl2(Ph3P)3 in [bmim][BF4] has turnover number = 540 h-1

– Metal complex recyclable

Cata ly st Substrate Produc tSolvent

Sy stemConv er sion (%) % ee

in s it u Ru-(S )-BINAP MeOH 100 62 (S)

[RuCl2- (S)- BINAP ]2•NEt3 MeOH 100 83 (S)

[RuCl2- (S)- BINAP ]2•NEt3 i -PrO H 100 64 (S)

in s itu Ru-(R )-B INAP [bmim][BF4]/MeOH 100 86 (S)

in s itu Ru-(R )-B INAP [bmim][BF4]/i -P rOH 99 69 (R )

1st recyc le [bmim][BF4]/i -P rOH 99 72 (R )

2nd recy cle [bmim][BF4]/i -P rOH 99 77 (R )

3r d rec ycle [bmim][BF4]/i -P rOH 99 70 (R )

[RuCl2- (S)- BINAP ]2•NEt3 [bmim][BF4]/i -P rOH 100 78 (S)

1st recyc le [bmim][BF4]/i -P rOH 100 84 (S)

2nd recy cle [bmim][BF4]/i -P rOH 90 79 (S)

3r d rec ycle [bmim][BF4]/i -P rOH 95 67 (S)

[Ru-(S )-BINAP ] [bmim][BF4]/i -P rOH 100 80 (S)

(R) CO2H

(S) CO2H

(S) CO2H

(S) CO2H

MeO MeO

(S)- Naproxen

CO2H

Ph

Ph

Ph

Ph

Ph

Ph

Ph

Ph

Ph

Ph

Ph

Ph

CO2H*

H2

[Ru-BINAP ][bmim][BF4]/Organic Solvent

PH2

PH2

B INAP

NNMe

BF4-

[bm im ][BF4]

Monteiro, A. L.; Zinn, F. K.; de Souza, R. F.; Dupont, J. Tetrahedron: Asymmetry, 1997, 8, 177-179.


Diels—Alder• Ionic liquid allows for catalyst recovery, rate acceleration, selectivity

enhancementO

O

O

O

Sc(OTf )3 ( 0.2 mol%)

s olvent, rt, 2h

Solvent Yield (%)

CD2Cl2 22

[bm im ][PF6] ( 1 eq.) + CD2Cl2 46

[bm im ][PF6] >99

Dienophi le Diene Pr oduct Endo:ex o Y ie ld(%)

>99:1 94

-94

>99:1 96

- 80

>99:1 84

>99:1 71

86 81 88 86 85

83 87 89 91 90

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

O

OO

O

O

OO

O

Song, C. E.; Shim, W. H.; Roh, E. J.; Lee, S.; Choi, J. H. Chem. Commun., 2001, 1122-1123.

NNMe Bu

PF6-

[bmim][PF6]


Olefin Epoxidation• (R,R)-Jacobsen’s catalyst immobilized in ionic liquid• Rate enhancement noticed over molecular solvents• Enantioselectivity and activity decrease upon reuse – possible catalyst

degredation over time• Co-solvent used for reactions below room temperature, because ionic liquid

solid at reaction temperature

O

N

t-Bu

t-Bu O

Mn

N

t-Bu

t-BuCl

HH

(R,R)-Jacobsen's Catalyst


Olefin Epoxidation

R3

R4R2

R1 O

R2 R4

R1 R3

(R, R)-Jacobsen's CatalystNaOCl

[bmim][PF6]-CH2Cl20°C

O

O

Ph Me

Substrate Time (h) Yield (%) % ee

286 96

4 72 94

4 72 84

3 72 86

4 77 84

NC

73 73 60 53 90 90 89 88

NNMe Bu

PF6-

[bmim][PF6]

O

O

Ph Me

NC

O

O

O

O

O

Product

Song, C. E.; Roh, E. J. Chem. Commun., 2000, 837-838.

O

N

t-Bu

t-Bu O

Mn

N

t-Bu

t-BuCl

HH

(R,R)-Jacobsen's Catalyst


Heck Reaction• 1996 – First example in ionic liquid by Kaufmann

– Used ammonium and phosphonium salts• Under basic conditions, deprotonation and formation of palladium

complexes of imidazolium carbenes facile• Competition of cationic and neutral pathways for enol ethers nonexistent

in ionic liquids – α-arylation (cationic) regiospecific

• 1999 – Seddon found tri-phasic system – organic: product, ionic liquid:catalyst, aqueous: salt

– Allows catalyst to be recovered and reused• Similar results for Suzuki, Stille, and Negishi (although yield decreases

on recycle experiments for Negishi)

Ph OBu

O

Pd

P

Ph

PI

Pd

P

Ph

P

Pd

I

PPh P

BuO

+I-

OBu

Pd

P

I

P

Pd

P

I

P

OBu

Ph

BuO

Ph

PhOBu

Ph OBu

Pd

Br

Br

N

N

N

N

Bu

Bu

Me

Me


Heck ReactionOBu A rX

DPPP (2 eq.)

NEt3 (1.2 eq)P d(OAc )2 ( 2.5 mol%)

[bm im ][BF4], 100°C, 18hAr

OBu

Ar OBu

! "

Br

I

B r

NC

Br

MeO 2C

Br

Me

OB r

H

O

Br

FBr

B r

Me

Subs trate Temperatur e (°C) Time (h) Conv er sion (%) !/" Y ie ld (%)

100 24 100 >99/1 95

80 24 100 >99/1 94

110 36 100 >99/1 94

120 36 100 >99/1 90

120 36 100 >99/1 92

100 24 100 >99/1 93

120 24 100 >99/1 97

100 24 100 >99/1 95

120 36 100 >99/1 88

PPh2Ph2P

DPPP

NNMe

BF4-

[bmim][BF4]

Xu, L.; Chen, W.; Ross, J.; Xiao, J. Org. Lett., 2001, 3, 295-297.


Swern Oxidation

N NN N

SS

O

H5IO6H2N

S

NH2

N NB r OH

!

N N OH2) AgOTf, MeCN

TfO-

MsClCs2CO3

MeCN

N N OMs

TfO-

2) NaOH/H2O

3) Me2SO4

1)

MeCN

TfO-

TfO -

OHO

1)

94%6 s teps

no chromatogr apy

98%

(COCl)2, NE t3CH2Cl2/MeCN

- 78°C

•Ionic liquid tethered “dimethyl sulfoxide” can be prepared with no chromatographyand no volatile (read: smelly) organosulfur reagents

•Products separated from ionic liquid by phase extraction with ether

•Reduced sulfide may be reoxidized and reused for at least 4 recycles with small lossof activity

•Also able to tether TEMPO catalyst

He, X.; Chan, T. H. Tetrahedron, 2006,62, 3389-3394


Swern OxidationN N N NS S

O

H5IO6

TfO- TfO-

OHO

OH

OH

H

OH

H

OHBnO

O

MeMe

Me

OH

O

O

H

O

H

OBnO

O

MeMe

MeO

90

88

95

82

90

87 86 81

Substrate Product Yield(%)

(COCl)2, NEt3CH2Cl2/MeCN

-78°C

He, X.; Chan, T. H. Tetrahedron, 2006,62, 3389-3394


RCM• Simple dissolution of catalyst not effective – catalyst soluble in organic solvents

& decomposes

HO O OMe

1) NaH, iP rI, DMF 90%2) Br2, HOAc , CH2Cl2, 98%3) LiAlH4, THF, 95%

O HO

Br1) B u3SnCHCH2, Pd(PPh3)4, P hMe, 75%2) NEt3, MsCl , CH2Cl23) L iB r, THF, DMF, 74% - 2 s teps

O Br

1) 1-methy limidazole, PhMe2) HPF6, H2O, 87% - 2 steps3) 1, CuCl , CH2Cl2, 78%

O

Ru

PCy 3Cl

ClN

NPF6

-

Ru

PCy 3

PCy 3

Cl

ClPh

1

Audic, N.; Clavier, H.; Mauduit, M.; Guillemin, J-C. J. Am. Chem. Soc., 2003, 125, 9248-9249.


Ring Closing Metathesis

O

Ru

RCl

ClN

NPF6

-

TsN

! 5 mol% cat.! 4h

RR[bmim][PF6], 60°C

TsN

TsN

CO2EtEtO2C

O

TsN

TsN

CO2EtEtO2C

O

TsN

>98 >98 >98 >98 >98 >98 97 92

>98 >98 >98 96 93 91 80

>98 >98 >98

>98 >98 >98 >98

94 78 48

Substrate Product Conversion(%)R

PCy3

PCy3

sIMesa

sIMes (25°C)a

PCy3

>98 >98 >98 95 95

>98 >98 83 33

a biphasic with toluene (25:75, [bmim][PF6] : toluene)

NNPF6

-

[bmim][PF6]

N NMes Mes

sIMes

Audic, N.; Clavier, H.; Mauduit, M.; Guillemin, J-C. J. Am. Chem. Soc., 2003, 125, 9248-9249.


The Future• Chiral functionalized ionic liquid

– Side chain or anion incorporates chirality– Asymmetric induction– Kinetic resolution

• Task-specific ionic liquids– Incorporate reagent or catalyst or substrate into

cation or anion– If substrate – can carry substrate on several steps,

immobilized in ionic liquid – allows for easyseparation/recovery

• Supercritical CO2– Used to extract product from ionic liquid phase

without using “molecular solvents”


Summary• Ionic liquids viable alternative to molecular

solvents in many reaction types• Ionic liquids allow for potential recovery/reuse

of catalyst (it may be the catalyst itself)• Rate enhancement, ease of product isolation,

recyclability of catalyst – ionic liquids couldbecome widely popular in near future


References• Properties:

– Handy, S. T. Current Organic Chemistry, 2005, 9, 959-988.– Dupont, J.; Spencer, J. Angew. Chem. Int. Ed., 2004, 43,

5296-5297.– Baudequin, C.; Brégeon, D.; Levillain, J.; Guillen, F.;

Plaquevent, J-C.; Gaumont, A-C. Tetrahedron: Asymmetry,2005, 16, 3921-3945. (Chiral ionic liquids)

– Welton, T. Chem. Rev., 1999, 99, 2071-2083.• Reactions:

– Sheldon, R. Chem. Commun., 2001, 2399-2407.– Song, C. E. Chem. Commun., 2004, 1033-1043.– Lee, S. Chem. Commun., 2006, 1049-1063. (Functionalized

ionic liquids)– Miao, W.; Chan, T. H. Acc. Chem. Res., ASAP (Ionic liquid-

supported synthesis)– Jain, N.; Kumar, A.; Chauhan, S.; Chauhan, S. M. S.

Tetrahedron, 2005, 61, 1015-1060.

ionic liquids in organic synthesis - university of north ... · pdf filewhat is an ionic...

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