Copyright 2012 James Ashenhurst masterorganicchemistry.

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RMgX Grignard

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O M OR Ester enolate OH R O OR R

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O M R Ketone enolate OH O R R

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NR2 R Enamine OH NR2 R RO R RO O

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O M R

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RNH2 amine (primary amine) N R R R H R

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MCN Cyanide OH H CN

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ROH/ ROM alcohol/ alkoxide RO R OR H

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H2O/ MOH water/ hydroxide HO R OH H R

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NaBH4 Sodium borohydride OH H H R

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LiAlH4 Lithium aluminum hydride OH H H

keto ester enolate

O O

OH H R R

Aldehyde

2 alcohol

Aldol Reaction

Aldol Reaction

heating under basic conditions will lead to elimination of OH - Aldol condensation also note that reaction can be reversible under basic conditions : Retro-aldol reaction O OH Cl R 3 alcohol R R R O O OR R O O R R O NR2 R

Knoevenagel Condensation

Imine (aldimine)

Cyanohydrin

Acetal Requires acid catalysis to form

Hydrate (usu. thermodynaically disfavored, except for electron poor aldehydes) If aldehyde is enolizable, hydroxide can form enolate. O

1 alcohol

1 alcohol

O RO O

OH R R R

O NHR R

O CN R

O OR R

OH OH H 2 alcohol R H R

OH H H 2 alcohol

Acyl chloride

keto ester

Amide (Schotten-Bauman reaction) O R R NHR

Acid nitrile

Ester

Carboxylic acid

O O R'

OH R R R 3 alcohol OH R

O OR R

O R R

NR2 R RO

O R CN R

O OR R

O OH Borderline R

OH H H

Anhydride O

O OH R R' O OR R OH R' O R R OH R NR2 R RO R O

R O OR R

Amide N R R R'

Acid nitrile OH R CN R' Cyanohydrin

Ester RO R OR R'

Carboxylic Acid HO R OH R R OH R' H

1 alcohol OH R R' H

R'

R'

Ketone

3 alcohol

Aldol Reaction

Aldol Reaction

Note: best when ketones are identical or when only one can enolize (to avoid scrambling) O O R O OR R O O R R O NR2 R RO O OH R

Imine (ketimine)

Acetal Requires acid catalysis

Hydrate see above: even less favored than with aldehydes due to sterics O

2 alcohol

2 alcohol

R , unsaturated ketone (enone) O

Varies with conditions: 1,2 adduct is kinetic pdt.

O R RHN NC

O R RO

O R RO

Varies with conditions: 1,2 adduct is kinetic product, 1,4 adduct is thermodynamic.

Michael Reaction

Michael Reaction O R

Note: in both cases, very prone to the reverse reaction (elimination) O O NHR NR R OR'

Note: Easily reversible O R OH NR R OH H H

OH OR R R R R

O OR R

O R Borderline Borderline R

Ester O

3 alcohol

keto ester: Claisen Condensation

1,3 diketone: Claisen Condensation

Amide

O OH Deprotonation Deprotonation Deprotonation NR Deprotonation R NHR NR

Transesterification Saponification Can be done under basic (basic conditions) or acidic conditions. Can also hydrolyze with aqueous acid O R OR' NR

1 alcohol OH H H 1 alcohol R

Carboxylic acid

Usually requires dehydration agent (e.g. DCC) 1 and 2 amides: deprotonation 3amides: NR 1 and 2 amides: deprotonation 3amides: NR NR

Fischer esterification (requires acid, heat) Borderline reaction: requires strong acid, alcohol as solvent, heat O R OH NR

H R NH2 H Amine

NH2

Deprotonation

NR

NR

NR

Amide O O OR Enolate Alkylation R R R NR2 R RO R Alkyl halide Enolate Alkylation Stork enamine reaction note: capable of alkylating a second time Amine caution! product is a good nucleophile; can obtain multiple alkylations Williamson Ether Synthesis requires basic conditions O O R R NHR R CN R OR

Amide Hydrolysis Requires strong conc. acid, heat R OH NR

Mix of addition /deprotonation

requires basic conditions

Alkane