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CARBANIONES

1,2-addition (direct addition)

nucleophile attacks carbon of C=O

1,4-addition (conjugate addition)

nucleophile attacks -carbon

Nucleophilic Addition to

-Unsaturated Aldehydes and Ketones

H Y+C C

C

O

1,2-addition

C C

C

OH

Y

formed faster

major product under

conditions of kinetic

control (i.e. when

addition is not readily

reversible)

H Y+C C

C

O

1,4-addition

C C

C

OH

Y

- enol goes to keto form under

reaction conditions

- keto form is isolated product of

1,4-addition is more stable than

1,2-addition product

observed with strongly basic nucleophiles

Grignard reagents

LiAlH4

NaBH4

Sodium acetylide

strongly basic nucleophiles add irreversibly

1,2-Addition

Example

O

CH3CH CHCH + HC CMgBr

1. THF

2. H3O+

OH

CH3CH CHCHC CH

(84%)

observed with weakly basic nucleophiles

cyanide ion (CN–)

thiolate ions (RS–)

ammonia and amines

azide ion (N3–)

weakly basic nucleophiles add reversibly

1,4-Addition

Example

KCNethanol,

acetic acid

(93-96%)

O

C6H5CH CHCC6H5

O

C6H5CHCH2CC6H5

CN

via

C6H5CH CC6H5

CN

••

–

O••••

CH

C6H5CH CC6H5

CN

–O•••••

•

CH

Example

O

CH3

C6H5CH2SH HO–, H2O

(58%)

O

CH3

SCH2C6H5

via

–

O•••••

•

CH3

SCH2C6H5

CH3

SCH2C6H5

–

O••••

••

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The Michael AdditionThe Michael reaction is a useful method for forming C-C bonds.

It is also useful in that the product of the reaction can undergo

an intramolecular aldol condensation to form a six-membered

ring. One such application is called the Robinson annulation.

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Michael reactions form 1,5-dicarbonyl compounds:

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Mechanism for the Michael

Addition Reaction

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Example

O

H2C CHCCH3

CH3

O

O

KOH, methanol

+

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The Robinson Annulation

The Robinson annulation affords a product with a

fused 2-cyclohexenone ring:

Annulation: addition of a new ringfused 2-cyclohexenone

ring

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Robinson annulation mechanism:

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The Stork Enamine Reaction

Enamines are used in place of enolates in these Michael

addition reactions:

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Intramolecular Condensation

and Addition Reaction

The Dieckmann condensation:

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Intramolecular Aldol Additions

1,4-Diketones afford five-member rings:

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1,6-Diketones also afford five-member rings:

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1,5- and 1,7-diketones afford six-member rings:

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Decarboxylation of

3-Oxocarboxylic Acids

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Acid catalyzes the intramolecular transfer of the proton:

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The Malonic Ester Synthesis: preparation of

carboxylic acids.

A malonic ester synthesis forms a carboxylic acid with

two more carbon atoms than the alkyl halide:

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Mechanism for the malonic ester synthesis:

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Preparation of Carboxylic Acids with Two

Substituents Bonded to the -Carbon

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The Acetoacetic Ester Synthesis: preparation of

ketones

Synthesis of Methyl Ketone by Acetoacetic Ester

Synthesis

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Mechanism for the acetoacetic ester synthesis:

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Enolate

Reactions of

Carboxylic Acids

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Decarboxylation and Synthesis

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Designing a Synthesis to Make New

Carbon–Carbon Bonds

Synthetic goal:

Strategies:

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Solution:

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Synthetic goal:

Solution:

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Synthetic goal:

Solution: