Synthetic reagents

Dr. L. Satish Kumar Achary

Asst. Professor

Department of Chemistry

CV Raman Global University

Advanced Organic ChemistryM.Sc. 3rd sem

Organometallic reagents

Contents

➢ Organosilicon

➢ Synthesis.

➢ Applications.

➢ Organotin

➢ Synthesis.

➢ Applications.

➢ Tebbe reagent2

❑ Organosilicon

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Trimethylsilyl chloride

(TMSCl)

tert-butyldimethylsilyl chloride

(TBDMSCl)

Diphenylmethylsilyl

chloride (DPMSCl)

Triisopropylsilyl chloride

(TMSiCl)

SiSi

Si Si

4

❑ Si forms weaker bond with electropositive elements w.r.t C.

❑ Si has low E.N than C. Thus C-Si bond is polar.

❑ C-Si bond length 1.89 Å, steric interaction between Nu- and

substrate is less. C-C bond length 1.53 Å.

❑ Silicon has vacant d-orbital which provides a target for Nu-.

C-Si

C-F

C-Cl

C-OH

F-

Cl-

OH-

StableNaF, HF, KF, nBu4NF,

NaCl, HCl, NaOH,

KOH

❑ Silicon stabilizes α-carbanion with vacant d-orbital and β-carbocation with σ-bonding orbital.

5

❑ Synthesis

SiCl4

Chloro compounds are the starting materials for the preparation of

organosilicon compound.

3CH3MgCl (CH3)3SiCl+

❑ Applications

(1) As nucleophilic reagent for O-C bond cleavage

Ether reacts with the reagent to afford the alkyl iodide and

trimehylsilyl ether.

+ +

+

Ether

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+

TMSI TMSI

Epoxide

Epoxides give corresponding alkene.

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Acetal

Acetal can be converted in to ketones.

(2) In nucleophilic addition reaction

Addition reaction with carbonyl compound.

α-iodotrimethylsilyl ester

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(3) Protecting group for alcohols as TMS ester

TMSCl (1.2 equvalent) TMSCl (1.3 equvalent)

t-butyldimethylsilyl halide (TBDMS-X) is a bulky reagent which

preferabily protect primary alcohol with imidazole in DMF.

TBDPSCl

Imidazole/DMF

9

1. TBDMSC

2. DDQ

3. Cl-

Deprotection can easily be done by the treatment of tetra-n-

butaylammonium flouride (TBAF), citric acid and Cl-.

TBAF/Et3N

CH2Cl2

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Silylenol ethers

Trimethylsilyl enol ether of aldehyde and ketones are usually

formed from carbonyl compound. An additional base is used.

Me3SiI/Et3N

DMF

Me3SiI/Et3N

DMF

Product depends upon base.

If base is bulkier, less substituted sillyl enol ether is the major

product. (LDA)

If base is small, more substituted sillyl enol ether is the major

product. (Et3N)

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Regioselectivity

Alkylation of carbonyl compound

1.Base, 2. R3SiX

3. R-X, 4. H3O+

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1.LDA, 2. Me3SiX

3. CH3-X, 4. H3O+

1. Et3N, 2. Me3SiX

3. Ph--X, 4. H3O+

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Peterson’s olefination (α-carbanion)

Li-Mg derivative of α-silylCarbonyl

CompoundOlefins

Alkenyl silane(β-carbocation)

Alkenyl silane undergoes electrophilic substitution reaction via β-

carbocationE+

E+X-

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Electrophillic substitution reaction catalyzed by Lewis acid.

AlCl3

AlCl3

AlCl3

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Allyl silane (β-carbocation)

E+ X-

Allyl silane undergoes electrophilic substitution reaction via β-

carbocation.

Electrophillic substitution reaction catalyzed by Lewis acid.

AlCl3

AlCl3

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Bu3–Sn–HTributyltin hydride

❑ Organotin

Sn has more metallic character with +4 oxidation state and forms

stable organic compounds.

Size if Tin is larger than Si and C due to which the bond between

Sn and C can be easily polarized.

❑ Synthesis

4Bu3SnCl

Tributyltin hydride is prepared from tributyltin chloride and LiAlH4.

LiAlH4+ 4Bu3SnH LiAlCl4

+

Tributyltin hydride is generally used as reducing agent and used

as source of hydrogen radical.

Initiator: AIBN (Azobisisobutyronitrile).

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❑ Applications

(1) Replacement of halo group

Tributyltin hydride replaces halo group from all organo halo

compounds.

R-X R-HBu3Sn-H

AIBN

X = F, Cl, Br, I.

Bu3Sn-H

AIBN

Bu3Sn-H

AIBN

Bu3Sn-H

AIBN

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Bu3Sn-H

AIBN

Bu3Sn-H

AIBN

Reactivity order

Benzyl halide > allyl halide > 3° alkyl halide > 2° alkyl halide >

1° alkyl halide > aryl halide > Vinyl halide > Alkenyl halide.

Bu3Sn-H

AIBN+ +

If halocompound having unsaturation, substitution may

accompanied by cyclisation.

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Bu3Sn-H

AIBN +

Bu3Sn-H

AIBN

(2) Replacement of nitro group

Tributyltin hydride replaces nitro group from new C-C bond.

Bu3Sn-H

AIBN

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(2) Replacement of sulphide group

Bu3Sn-H

AIBNR-SR1 R-H

Bu3Sn-H

AIBN

Bu3Sn-H

AIBN

Bu3Sn-H

AIBN

If there is an unsaturation in the sulphide, replacement of sulphide

followed by cyclization takes place.

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(2) Reduction of acid halide

Bu3Sn-H

AIBN

Acid halide gives aldehydes.

(3) Reduction of carbonyl compound

Bu3Sn-H

AIBN

Bu3Sn-H

AIBN

Carbonyl compound converted into alcohol.

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❑ Tebbe reagent

❑ The tebbe reagent is the organometallic compound.

❑ It is used in the methylenation of carbonyl compounds.

❑ Formula :C13H18AlClTi

❑ Synthesis

Titanocene dichloride reacts with trimethyl aluminium in toluene.

Me3Al

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❑ Applications

❑ Methylation of carbonyl compound

base or

without

base❑ Mechanism in presence of base

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❑ Mechanism in absence of base

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❑ Methylation of amides

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❑ Reactivity of carbonyls

> > >

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1 eq.

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