Synthesis of Ketones From Acids

1. Synthesis of Ketones From Acids Dry THF RCOO- Li+ RCOOH LiOH + Dry THF + R’- Li+ RCOO- Li+ DIANION IMPORTANT: NO WATER TO HERE HOH H+ GEM DIOL

2. Example of Ketone from Acid

3. Synthesis Using Acid and RLi Convert PhEt to Cyclopropyl ethyl ketone LiOH 2. EtLi 3. HOH H+ How could one prepared benzoic acid From ethyl benzene? Side-chain oxidation!!!! Appears as if we could start with benzoic acid and introduce ethyl group by EtLi.

4. Synthesis of Aldehydes and Ketones from Acid Chlorides 1.Preparation of acid chlorides R = almost anything!! H, Alkyl, Aryl, etc 2. Preparation of aldehydes - bulky reducing reagents Reduction to ROH does not occur - steric -

5. Synthesis of Ketones Recall that ketones react with acid chlorides to give alcohols. TO STOP AT KETONE STAGE, NEED A MILDER ORGANOLITHIUM

6. USE OF ORGANO CUPRATES Rli + CuI --------> R2CuLi + STOPS: addition to acid chloride is much faster than addition to ketone.

7. Example

8. Reactions of Carbonyls Nucleophilic addition - pages 797-800 Base-promoted additions Nucleophilic anion attacks C=O to give alkoxide which is neutralized to alcohol by acidic work-up. Acid-catalyzed additions increases electrophilicity of carbonyl group Relative rate of addition: HCHO > RCHO> RCOR

9. WITTIG REACTION + Ph3P-O