Carbonyl chemistry- reduction Flashcards
What allows one carbonyl to react over another
- Difference in reactivity
2. Chemoselectivity
Would NaOH react more readily with ester or amide functional group in compound
- Ester over amide
2. Ester is more reactive as donates less back into the carbon so the carbon is more electrophilic
What are metal hydrides
- One of the most common reducing agents
- Source of ‘H’ nucleophile
- Have different reactivities
- The more reactive the less selective it is
Order LiAlH4, LiBH4 and NaBH4 by reactivity
- LiAlH4 is most reactive as it has a lewis acidic carbanion and a nucleophilic anion
- Then LiBH4
- Then NaBH4
What are Lewis acid hydrides
- Charge neutral lewis acids
- Only source of H when they form Lewis acid-base complex
- Useful for reduction of electron rich carbonyl derivatives
Give two examples of lewis acid hydrides
- DIBAL- forms a bridged dimer
2. BH3 (borane)- forms a bridged dimer
What reducing reagents react with Aldehydes
- LiAlH4- readily reacts
- LiBH4- readily reacts
- NaBH4- readily reacts
- BH3- slowly reacts
What reducing reagents react with ketones
- LiAlH4- readily reacts
- LiBH4- readily reacts
- NaBH4- readily reacts
- BH3- slowly reacts
What reducing reagents react with esters
- LiAlH4- readily reacts
- LiBH4- readily reacts
- NaBH4- slowly reacts
- BH3- slowly reacts
What reducing reagents react with amides
- LiAlH4- readily reacts
- LiBH4- no reaction
- NaBH4- no reaction
- BH3- readily reacts
What reducing reagents react with carboxylic acids
- LiAlH4- slowly reacts
- LiBH4- no reaction
- NaBH4- no reaction
- BH3- readily reacts
Describe the reactivity of LiAlH4
- Reacts with everything
- Best with higher reactivity carbonyls
- Slow reaction with carboxylic acids
Describe reactivity of LiBH4
- Reacts with the most reactive carbonyls
2. Doesn’t react at all with amides or carboxylic acids
Describe reactivity of NaBH4
- Reacts with most reactive carbonyls
- Slow react with esters
- Doesn’t react with amides or carboxylic acids
Describe reactivity of BH3
- Reacts best with less reactive carbonyls
2. Slow reactions with esters, ketones and aldehydes
What is BH3 useful for
- Good at reducing less electron rich in presence of more reactive carbonyls
How are aldehydes and ketones reduced to primary and secondary alcohols
- Nucleophilic addition
- One hydrogen equivalent
- Secondary alcohol produced contains a stereogenic centre
How are esters, amides and carboxylic acids reduced
- Nucleophilic substitution first
- Then nucleophilic addition
- 2 hydrogen equivalents
How can aldehydes and ketones be reduced to alkanes
- Clemmensen reaction
2. Wolff-Kishner reaction
Describe the clemmensen reaction
- Zn(Hg) and concentrated HCl- very harsh conditions
2. Very harsh conditions
Describe the Wolff- Kishner reaction
- N2H4.H2O (>10 eq)
- KOH (>5 eq)
- > 180 degrees
- Very harsh conditions
What can cyanide be used for
- Generate a new c-c bond and cyanohydrin functionality
2. It is a carbon based nucleophile
Describe how cyanide can be used to convert an aldehyde or ketone
- Reaction is reversible
- Add NaCN, H2O and HCl to aldehyde or ketone
- Produces a alcohol with a CN group
Why is the conversion of an aldehyde/ketone using cyanide reversible
- The CN group is a good leaving group
2. This means it is reversible
What is formed if you add acid and water to a nitrile
- A carboxylic acid is produced
2. Need to be around 100 degrees
How can a nitrile undergo functional group interconversion to become a carboxylic acid
- Add acid (H2SO4), Water and 100 degrees
2. Forms a carboxylic acid containing the same R group
How can alkyl groups be added to carbonyls
- Organometallic reactions
2. Most common are either lithium or magnesium derived
What are the properties of Li/Mg organometallics
- Not ionic but covalent
- Very strong nucleophiles
- Very strong bases- pKa of conjugate acid >40
- Therefore can deprotonate acid C-H bonds to form new organometallic reagents
What is a grignard reagent
- Organomagnesium compounds with the general formula RMgX
2. X is a halide
How is a Grignard reagent formed
- Addition of magnesium to alkyl halides (I,Br,Cl) in etheric solvents (Et2O)
- Addition to aryl halides (I,Br) in tetrahydrofuran (THF)
- Involves insertion of magnesium into carbon-halogen bond (oxidative insertion)
Why are the particular solvents used in formation of Grignard
- Et2O used for alkyl halides- don’t need high boiling solvent to keep heat in as not a lot of heat is needed
- THF for aryl halides- holds heat in solution for aryl halides which need a higher heat
How can you make organolithium reagents
- Uses an oxidative insertion process
- substitution of Lithium in alkyl halides (I,Br,Cl) in etheric solvents (Et2O)
- Substitution of lithium in aryl halides (I,Br) in tetrahydrofuran (THF)
- Replaces the halide completely
- Also can use lithium halogen exchange as another method
What do you need to be careful about when making Mg/Li organometallic reagents
- Cannot have any acidic or carbonyl functional groups present
- As the reagents are very basic and reactive
- These need to be protected
How are aldehydes and ketones reduced using organometallic reagents
- Nucleophilic addition
2. Form secondary and tertiary alcohols
How is an ester reduced using an organometallic reagent
- First reduction of OR group to form ketone by nucleophilic substitution
- Then reduced further
- 2 equivalents of reducing agent
- Forms a tertiary alcohol
How is an amide reduced using an organometallic reagent
- First nucleophilic substitution to form aldehyde or ketone
- Then react further
- One reducing equivalent
How is a carboxylic acid reduced using an organometallic reagent
- It isn’t
What is a Wittig reaction
- Use of phosphonium salts to convert aldehydes/ketones to alkenes
- Utilises phosphorous ylide as the key reagent which is prepared in situ from phosphonium salt
- Phosphonium salt is easily prepared from alkyl halide and phosphine - SN2 reaction
How can the nature of the substituent on the ylid control E/Z geometry
- R groups= H, OR, alkyl = Z-alkene
2. R groups= alkyl = E-alkene
Why does the difference in R-groups affect the stereochemistry
- If R group= H, OR, alkyl, the phosphorous ylid is stabilised by delocalisation of -ve charge
- If R group= alkyl only, the phosphorous ylid is unstabilised as the -ve charge can’t be delocalised by conjugation
What is a ylide
- A ylide is a species which contains two oppositely charged atoms bonded directly to each other.
