Reduction of Aldehydes and Ketones 1 19.8 Reduction of Aldehydes and Ketones to Alcohols

Reduction of Aldehydes and Ketones

119.8 Reduction of Aldehydes and Ketones to Alcohols

Reduction with LiAlH4 and NaBH4

219.8 Reduction of Aldehydes and Ketones to Alcohols

Reduction with LiAlH4

• LiAlH4 serves as a source of hydride ion (H:-)

• LiAlH4 is very basic and reacts violently with water; anhydrous solvents are required

319.8 Reduction of Aldehydes and Ketones to Alcohols

Reduction with LiAlH4

• Like other strong bases, LiAlH4 is also a good nucleophile

• Additionally, the Li+ ion is a built-in Lewis-acid

419.8 Reduction of Aldehydes and Ketones to Alcohols

Reduction with LiAlH4

• Each of the remaining hydrides become activated during the reaction

519.8 Reduction of Aldehydes and Ketones to Alcohols

Reduction with NaBH4

• Na+ is a weaker Lewis acid than Li+ requiring the use of protic solvents

• Hydrogen bonding then serves to activate the carbonyl group

619.8 Reduction of Aldehydes and Ketones to Alcohols

Reduction with LiAlH4 and NaBH4

• Reactions by these and related reagents are referred to as hydride reductions

• These reactions are further examples of nucleophilic addition

719.8 Reduction of Aldehydes and Ketones to Alcohols

Selectivity with LiAlH4 and NaBH4

• LiAlH4 reduces all carbonyl groups

• NaBH4 is less reactive– Reduces

• Aldehydes• Ketones• Esters (slowly)

– Does not reduce• Carboxylic acids• Amides• Nitro groups• Alkyl halides• Alkyl tosylates

819.8 Reduction of Aldehydes and Ketones to Alcohols

Problems

• Which reducing agent, LiAlH4 or NaBH4 is more appropriate for reduction of the following reagents? Draw the products.

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Reduction by Catalytic Hydrogenation

• Hydride reagents are more commonly used• However, catalytic hydrogenation is useful for

selective reduction of alkenes

1019.8 Reduction of Aldehydes and Ketones to Alcohols

Grignard Addition

• Grignard reagents with carbonyl groups is the most important application of the Grignard reagent in organic chemistry

1119.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents

Grignard Addition

1219.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents

Importance of the Grignard Addition

• This reaction results in C-C bond formation

• The synthetic possibilities are almost endless

1319.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents

Importance of the Grignard Addition

1419.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents

Grignard Addition

• R-MgX reacts as a nucleophile; this group is also strongly basic behaving like a carbanion

• The addition is irreversible due to this basicity

1519.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents

Problems

• Give the products for the following Grignard reactions:

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Organolithium and Acetylide Reagents

• These reagents react with aldehydes and ketones analogous to Grignard reagents

1719.9 Reactions of Aldehydes and Ketones with Grignard and Related Reagents

Problems

• Give the products for the following rxns:

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Reactions with Amines

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Secondary Amine

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Reactions with Primary Amines

• Dehydration is typically the rate-limiting step

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Reactions with Secondary Amines

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Problems

1) Draw the products for the following reactions:

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2) Draw the mechanism for the formation of the imine in the previous question

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