Organic I - nucleophilic addition to carbonyls

NO MECHANISMS JUST CONDITIONS AND EXPLANATIONS

What are the two main steps in a nucleophilic addition to a carbonyl?

• Nucleophilic attack on the carbonyl group (nucleophilic addition)

• Protonation of the anion

What are the electronic changes during a nucleophilic addition reaction?

• Pi bonds are lost to form a new sigma bond - usually energetically favourable

• sp2 centres (unsaturated) in carbon and oxygen are changed to sp3 centres (saturated)

From which angles can a nucleophile attack the carbonyl carbon?

• Above the plane

• Below the plane

• 109° to the C=O bond from behind the atom - Burgi-Dunitz trajectory

Why is the nucleophile restricted to these locations when attacking a carbonyl carbon?

• The pi* antibonding orbital is the LUMO

• The nucleophile puts two electrons into the LUMO when forming a bond

How do structural differences between aldehydes and ketones affect their nucleophilic reactivity?

• Both will undergo nucleophilic addition

• Aldehydes will be more reactive with nucleophiles / ketones will be less reactive with nucleophiles

• Aldehydes have less crowded centres - less steric hindrance / ketones have more crowded centres - more steric hindrance

• +I inductive effect from R groups reduces the delta+ carbon centre - occurs more in ketones

How are cyanohydrins formed using nucleophilic addition?

• HCN components are added to C=O in either an aldehyde or ketone

• Conditions: NaCN + H2O in HCl

• NaCN dissociates into Na+ and CN- : CN- reacts initially

• Reaction exists in an equilibrium

How is the cyanohydrin formation equilibrium affected by the reagents?

• Reaction is less favourable with ketones than aldehydes (lower Keq)

• More difficult to form cyanohydrins with ketones

What are the benefits of using H- versus BH4-?

• H-: not a good nucleophile; only used as a base from either NaH or KH

• BH4-: good source of nucleophilic hydrogen (‘softer’ source); used as NaBH4 in alcohol solvents or water

Which reducing agents are used to protonate compounds, and what solvents does either use?

• NaBH4: used to protonate aldehydes and ketones; used in an alcohol solvent or water

• LiAlH4: used to protonate less reactive carbonyls; used in an aprotic solvent

What does protonation of aldehydes and ketones form?

• Aldehydes: primary alcohol (terminal)

• Ketones: secondary alcohol