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Gilmans ReagentsLithium dimethyl cuprate / Lithium dimethyl copper /Dimethyl copper lithium

2/21/2011 Dr. Hitesh D. Patel 1

Cu I + Li CH3 Ether- 78 C

o Cu CH3 + Li I

Li CH3 Ether - 78 Co

( CH3 )2 Cu Li

Li CH3 + Cu I0 C

o

N2

( CH3 )2 Cu Li

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Replacement of Iodine / Bromine

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I

( CH3

)2

Cu LiCH3

Br

Br ( CH3 )2 Cu Li

CH3

CH3

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2/21/2011 Dr. Hitesh D. Patel 4

H5C6 C

C

H

H Br

( CH3 )2 Cu LiH5C6 C

C

H

H CH3

CH3CH3

CH3

CH3

CH2OH

H

I

( CH3 )2 Cu Li

CH3CH3

CH3

CH3

CH2OH

H

CH3

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Reaction with oxiranes (epoxide)OCH3

2 ( CH3 )2 Cu Li

OH

CHCH2CH3

CH3

OCH2

CH3

2 ( CH3

)2

Cu Li

CH3

CH2

CH

OH

CH2 CH3

O

CH3 COOC2H5

2 ( CH3 )2 Cu LiOH

CHCH

CH3COOC2H5

CH3

O

(CH2) C CH3

O

2 ( CH3 )2 Cu LiOH

CHCH2 (CH2) C CH3

O

CH3

2/21/2011 Dr. Hitesh D. Patel 5

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Addition to ,- acetylenic esterR C C COOCH3 + ( CH3 )2 Cu Li

R

CH3

COOCH3

Cu

( CH3 )2 Cu Li

R

CH3

COOCH3

CH3

2/21/2011 Dr. Hitesh D. Patel 6

8/2/2019 Reagents - Lect. III, IV, V

7/412/21/2011 Dr. Hitesh D. Patel 7

CH3

CH2CH3

O

CH3

( CH3 )2 Cu Li

CH3

CH2

CH3

O

CH3

CH3

O

COOH

( CH3 )2 Cu Li

O

COOH

CH3

H

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Methyl ketones from carboxylic

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Sodium cyanoborohydride

[NaBH3CN]

Sodium cyanoborohydride is the inorganiccompound with the formula NaBH3(CN). Thiscolourless salt is widely used in organic synthesis forthe reduction ofimines.

2/21/2011 Dr. Hitesh D. Patel 9

http://en.wikipedia.org/wiki/Inorganic_compoundhttp://en.wikipedia.org/wiki/Inorganic_compoundhttp://en.wikipedia.org/wiki/Sodiumhttp://en.wikipedia.org/wiki/Boronhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Organic_synthesishttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Organic_synthesishttp://en.wikipedia.org/wiki/Iminehttp://en.wikipedia.org/wiki/File:Sodium-cyanoborohydride-2D.pnghttp://en.wikipedia.org/wiki/Iminehttp://en.wikipedia.org/wiki/Organic_synthesishttp://en.wikipedia.org/wiki/Organic_synthesishttp://en.wikipedia.org/wiki/Organic_synthesishttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Boronhttp://en.wikipedia.org/wiki/Sodiumhttp://en.wikipedia.org/wiki/Inorganic_compoundhttp://en.wikipedia.org/wiki/Inorganic_compoundhttp://en.wikipedia.org/wiki/Inorganic_compound

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The reagent may be prepared, either by treatingsodium cyanidewith borane.

By reacting sodium borohydride with mercury(II)cyanide.

Owing to the presence of the electron-withdrawing cyanide substituent, [B(CN)H3]

is farless nucleophilic than is [BH4]

, as found insodium borohydride.

2/21/2011 Dr. Hitesh D. Patel 10

http://en.wikipedia.org/wiki/Sodium_cyanidehttp://en.wikipedia.org/wiki/Boranehttp://en.wikipedia.org/wiki/Mercury(II)_cyanidehttp://en.wikipedia.org/wiki/Mercury(II)_cyanidehttp://en.wikipedia.org/wiki/Cyanidehttp://en.wikipedia.org/wiki/Sodium_borohydridehttp://en.wikipedia.org/wiki/Sodium_borohydridehttp://en.wikipedia.org/wiki/Sodium_borohydridehttp://en.wikipedia.org/wiki/Sodium_borohydridehttp://en.wikipedia.org/wiki/Cyanidehttp://en.wikipedia.org/wiki/Mercury(II)_cyanidehttp://en.wikipedia.org/wiki/Mercury(II)_cyanidehttp://en.wikipedia.org/wiki/Mercury(II)_cyanidehttp://en.wikipedia.org/wiki/Boranehttp://en.wikipedia.org/wiki/Sodium_cyanidehttp://en.wikipedia.org/wiki/Sodium_cyanidehttp://en.wikipedia.org/wiki/Sodium_cyanide

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Sodium cyanoborohydride is a mild reducing agentthat converts imines to amines.

It can be used to exchange the oxygen for an aminegroup on the carbonyl carbon of aldehydes orketones when reacted with ammonia or a primary

amine. Selectivity is achieved at mildly basic solutions

(pH 7-10).

Owing to this selectivity, the reagent is ideal forreductive aminations.

This reduction is known sometimes as the BorchReaction.

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http://en.wikipedia.org/wiki/Iminehttp://en.wikipedia.org/wiki/Aminehttp://en.wikipedia.org/wiki/PHhttp://en.wikipedia.org/wiki/Reductive_aminationhttp://en.wikipedia.org/wiki/Reductive_aminationhttp://en.wikipedia.org/wiki/Reductive_aminationhttp://en.wikipedia.org/wiki/Reductive_aminationhttp://en.wikipedia.org/wiki/PHhttp://en.wikipedia.org/wiki/Aminehttp://en.wikipedia.org/wiki/Imine

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The salt is mildly water-sensitive, but toleratesaqueous conditions.

In addition, sodium cyanoborohydride is often used in

hydrogenolysis reactions, such as the opening ofacetals.

Reductive amination (also known as reductive

alkylation) is a form of amination that involves theconversion of a carbonyl group to an amine via anintermediate imine. The carbonyl group is mostcommonly a ketone oran aldehyde.

2/21/2011 Dr. Hitesh D. Patel 12

http://en.wikipedia.org/wiki/Hydrogenolysishttp://en.wikipedia.org/wiki/Acetalshttp://en.wikipedia.org/wiki/Aminationhttp://en.wikipedia.org/wiki/Carbonylhttp://en.wikipedia.org/wiki/Aminehttp://en.wikipedia.org/wiki/Iminehttp://en.wikipedia.org/wiki/Ketonehttp://en.wikipedia.org/wiki/Aldehydehttp://en.wikipedia.org/wiki/Aldehydehttp://en.wikipedia.org/wiki/Ketonehttp://en.wikipedia.org/wiki/Iminehttp://en.wikipedia.org/wiki/Aminehttp://en.wikipedia.org/wiki/Carbonylhttp://en.wikipedia.org/wiki/Aminationhttp://en.wikipedia.org/wiki/Acetalshttp://en.wikipedia.org/wiki/Hydrogenolysis

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In this organic reaction, the amine first reacts with thecarbonyl group to form a hemiaminal species, whichsubsequently loses one molecule of water in a

reversible manner by alkylimino-de-oxo-bisubstitution, to form the imine. The equilibriumbetween aldehyde/ketone and imine can be shiftedtoward imine formation by removal of the formed

water through physical or chemical means. Thisintermediate imine can then be isolated and reduced

with a suitable reducing agent (e.g., sodiumborohydride). This is indirect reductive amination.

2/21/2011 Dr. Hitesh D. Patel 13

http://en.wikipedia.org/wiki/Organic_reactionhttp://en.wikipedia.org/wiki/Hemiaminalhttp://en.wikipedia.org/wiki/Reversible_reactionhttp://en.wikipedia.org/wiki/Alkylimino-de-oxo-bisubstitutionhttp://en.wikipedia.org/wiki/Alkylimino-de-oxo-bisubstitutionhttp://en.wikipedia.org/wiki/Iminehttp://en.wikipedia.org/wiki/Iminehttp://en.wikipedia.org/wiki/Sodium_borohydridehttp://en.wikipedia.org/wiki/Sodium_borohydridehttp://en.wikipedia.org/wiki/Sodium_borohydridehttp://en.wikipedia.org/wiki/Sodium_borohydridehttp://en.wikipedia.org/wiki/Sodium_borohydridehttp://en.wikipedia.org/wiki/Iminehttp://en.wikipedia.org/wiki/Iminehttp://en.wikipedia.org/wiki/Alkylimino-de-oxo-bisubstitutionhttp://en.wikipedia.org/wiki/Alkylimino-de-oxo-bisubstitutionhttp://en.wikipedia.org/wiki/Alkylimino-de-oxo-bisubstitutionhttp://en.wikipedia.org/wiki/Alkylimino-de-oxo-bisubstitutionhttp://en.wikipedia.org/wiki/Alkylimino-de-oxo-bisubstitutionhttp://en.wikipedia.org/wiki/Alkylimino-de-oxo-bisubstitutionhttp://en.wikipedia.org/wiki/Alkylimino-de-oxo-bisubstitutionhttp://en.wikipedia.org/wiki/Reversible_reactionhttp://en.wikipedia.org/wiki/Hemiaminalhttp://en.wikipedia.org/wiki/Organic_reactionhttp://en.wikipedia.org/wiki/Organic_reactionhttp://en.wikipedia.org/wiki/Organic_reaction

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Properties

Molecular formula NaBH3CN

Molar mass 62.84 g/mol

Appearance white to off-whitepowder, hygroscopic

Density 1.20 g/cm3

Melting point 241 C decomp.

Solubility in water soluble

2/21/2011 Dr. Hitesh D. Patel 14

http://en.wikipedia.org/wiki/Chemical_formulahttp://en.wikipedia.org/wiki/Molar_masshttp://en.wikipedia.org/wiki/Hygroscopichttp://en.wikipedia.org/wiki/Densityhttp://en.wikipedia.org/wiki/Melting_pointhttp://en.wikipedia.org/wiki/Solubilityhttp://en.wikipedia.org/wiki/Waterhttp://en.wikipedia.org/wiki/Waterhttp://en.wikipedia.org/wiki/Solubilityhttp://en.wikipedia.org/wiki/Melting_pointhttp://en.wikipedia.org/wiki/Densityhttp://en.wikipedia.org/wiki/Hygroscopichttp://en.wikipedia.org/wiki/Molar_masshttp://en.wikipedia.org/wiki/Chemical_formula

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Reductive amination

2/21/2011 Dr. Hitesh D. Patel 15

O

+

CH3

NH

CH3

NaBH3CN

H N

CH3

CH3

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2/21/2011 Dr. Hitesh D. Patel 16

http://en.wikipedia.org/wiki/File:ReductiveaminationOverview.png

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Reduction of oxime

2/21/2011 Dr. Hitesh D. Patel 17

CH3 C CH2 CH3

N OH NaBH3CN

CH3 CH CH2 CH3

NH OH

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Reductive Amination of Aldehyde / Ketone

2/21/2011 Dr. Hitesh D. Patel 18

CH3

CH3

O + HN R2CH3

CH3

N+

R

R

NaBH3CNCH3

C

CH3

N

R

R

H

R1

R2

O + R NH OHR1

R2

N+

O-

R

NaBH3CN

R1

C

R2

N

OH

R

H

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Selective reduction of aliphatic

ketones to hydrocarbons

2/21/2011 Dr. Hitesh D. Patel 19

CH3 C ( CH2 )3 C O ( CH2 )6 CN

O ONaBH3CN

CH3 CH2 ( CH2 )3 C O ( CH2 )6 CN

O

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Alkyl hydrazine

2/21/2011 Dr. Hitesh D. Patel 20

N NH2

2 HCHO

NaBH3CN

N N

CH3

CH3

N NH2 +

H2C

H2C

CHO

CHO

NaBH3CN

N N

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2/21/2011 Dr. Hitesh D. Patel 21

CH3 ( CH2 )8 HC

OCH3

OCH3

NaBH3CN

CH3 ( CH2 )8 HC

OCH3

H

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Dess-Martin periodinane

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2/21/2011 Dr. Hitesh D. Patel 23

http://en.wikipedia.org/wiki/File:Dess-Martin-periodinane-3D-balls.pnghttp://en.wikipedia.org/wiki/File:Dess-Martin_periodinane.svg

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Preparation 2-Iodobenzoic acid is oxidized preferably byOxone, or

by KBrO3 to 2-iodoxybenzoic acid.

(Caution: 2-Iodoxybenzoic acid has been found to beimpact and heat sensitive, decomposing explosively.)

The 2-Iodoxybenzoic acid is then treated with amixture of acetic anhydride, acetic acid and p-

toluenesulfonic acid at 80-100 C for 40 min. Theresulted solids can be obtained via filtration andwashing with ether.

2/21/2011 Dr. Hitesh D. Patel 24

http://en.wikipedia.org/wiki/Oxidizehttp://en.wikipedia.org/wiki/Oxonehttp://en.wikipedia.org/wiki/2-iodoxybenzoic_acidhttp://en.wikipedia.org/wiki/Acetic_anhydridehttp://en.wikipedia.org/wiki/Acetic_acidhttp://en.wikipedia.org/wiki/P-Toluenesulfonic_acidhttp://en.wikipedia.org/wiki/P-Toluenesulfonic_acidhttp://en.wikipedia.org/wiki/P-Toluenesulfonic_acidhttp://en.wikipedia.org/wiki/Filtrationhttp://en.wikipedia.org/wiki/Diethyl_etherhttp://en.wikipedia.org/wiki/Diethyl_etherhttp://en.wikipedia.org/wiki/Filtrationhttp://en.wikipedia.org/wiki/P-Toluenesulfonic_acidhttp://en.wikipedia.org/wiki/P-Toluenesulfonic_acidhttp://en.wikipedia.org/wiki/P-Toluenesulfonic_acidhttp://en.wikipedia.org/wiki/P-Toluenesulfonic_acidhttp://en.wikipedia.org/wiki/P-Toluenesulfonic_acidhttp://en.wikipedia.org/wiki/Acetic_acidhttp://en.wikipedia.org/wiki/Acetic_acidhttp://en.wikipedia.org/wiki/Acetic_acidhttp://en.wikipedia.org/wiki/Acetic_anhydridehttp://en.wikipedia.org/wiki/Acetic_anhydridehttp://en.wikipedia.org/wiki/Acetic_anhydridehttp://en.wikipedia.org/wiki/2-iodoxybenzoic_acidhttp://en.wikipedia.org/wiki/2-iodoxybenzoic_acidhttp://en.wikipedia.org/wiki/2-iodoxybenzoic_acidhttp://en.wikipedia.org/wiki/2-iodoxybenzoic_acidhttp://en.wikipedia.org/wiki/2-iodoxybenzoic_acidhttp://en.wikipedia.org/wiki/Oxonehttp://en.wikipedia.org/wiki/Oxidize

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2/21/2011 Dr. Hitesh D. Patel 25

Preparations of Dess-Martin Periodinane

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Properties

Molecular formula C13H13IO8

Molar mass 424.14 g/mol

Appearancewhite powder, chips,crystals or crystalline

powder and/or chunks

Density 1.362 g/cm3 solid

Melting point 103 - 133 C

2/21/2011 Dr. Hitesh D. Patel 26

http://en.wikipedia.org/wiki/Chemical_formulahttp://en.wikipedia.org/wiki/Molar_masshttp://en.wikipedia.org/wiki/Densityhttp://en.wikipedia.org/wiki/Melting_pointhttp://en.wikipedia.org/wiki/Melting_pointhttp://en.wikipedia.org/wiki/Densityhttp://en.wikipedia.org/wiki/Molar_masshttp://en.wikipedia.org/wiki/Chemical_formula

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The Dess-Martin periodinane (DMP) is commerciallyavailable and decomposes only slowly.

But DMP is heat- and shock-sensitive, and shows anexotherm when heated >130 C.

2-Iodoxybenzoic acid (IBX), the impact-sensitiveintermediate in the synthesis of the Dess-Martin

periodinane, is available in a DMSO solution and isalso used as an oxidizing agent.

2/21/2011 Dr. Hitesh D. Patel 27

http://www.organic-chemistry.org/chemicals/oxidations/ibx-2-iodoxybenzoicacid.shtmhttp://www.organic-chemistry.org/chemicals/oxidations/ibx-2-iodoxybenzoicacid.shtmhttp://www.organic-chemistry.org/chemicals/oxidations/ibx-2-iodoxybenzoicacid.shtmhttp://www.organic-chemistry.org/chemicals/oxidations/ibx-2-iodoxybenzoicacid.shtmhttp://www.organic-chemistry.org/chemicals/oxidations/ibx-2-iodoxybenzoicacid.shtmhttp://www.organic-chemistry.org/chemicals/oxidations/ibx-2-iodoxybenzoicacid.shtm

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Uses and advantage of DMP Dess-Martin periodinane is mainly used as an oxidant

for complex, sensitive and multifunctional alcohols.

One of the reasons for its effectiveness is its highselectivity towards complexation of the hydroxylicgroup, which allows alcohols to rapidly perform ligandexchange; the first step in the oxidation reaction.

2/21/2011 Dr. Hitesh D. Patel 28

http://en.wikipedia.org/wiki/Oxidanthttp://en.wikipedia.org/wiki/Alcoholhttp://en.wikipedia.org/wiki/Hydroxidehttp://en.wikipedia.org/wiki/Ligandhttp://en.wikipedia.org/wiki/Ligandhttp://en.wikipedia.org/wiki/Hydroxidehttp://en.wikipedia.org/wiki/Alcoholhttp://en.wikipedia.org/wiki/Oxidant

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Its effectiveness as an oxidant is also due to itsversatility; having a broad scope of being able toconvert alcohols to carbonyl derivatives.

Its reactions and yield are also known to be clean andhigh respectively.

Work up is also clean and simple.

By products from the reaction can be removed easilyby precipitation, filtration or chromatography.

2/21/2011 Dr. Hitesh D. Patel 29

http://en.wikipedia.org/wiki/Carbonylhttp://en.wikipedia.org/wiki/Chromatographyhttp://en.wikipedia.org/wiki/Chromatographyhttp://en.wikipedia.org/wiki/Carbonyl

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2/21/2011 Dr. Hitesh D. Patel 30

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Dess-Martin Oxidation

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Mechanism of the Dess-Martin Oxidation

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2/21/2011 Dr. Hitesh D. Patel 33

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Name Reactions (Dess-Martin-Oxidation )

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http://www.organic-chemistry.org/namedreactions/dess-martin-oxidation.shtm

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Alcohols are oxidized to the corresponding carbonylcompounds

2/21/2011 Dr. Hitesh D. Patel 35

http://www.organic-chemistry.org/abstracts/literature/600.shtm

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2/21/2011 Dr. Hitesh D. Patel 36

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2/21/2011 Dr. Hitesh D. Patel 37

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2/21/2011 Dr. Hitesh D. Patel 38

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oxidation of secondary amides to imides

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http://www.organic-chemistry.org/abstracts/literature/984.shtm

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2/21/2011 Dr. Hitesh D. Patel 40

http://www.organic-chemistry.org/abstracts/literature/984.shtm

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2-substituted benzothiazoles from cyclization ofthioformanilides

http://www.organic-chemistry.org/abstracts/lit1/450.shtm