1. 19.12 Reactions of Esters with Grignard Reagents: Synthesis of Tertiary Alcohols Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

2. R MgX Grignard reagents react with esters C O – MgX + –– ++ R C O diethyl ether OCH 3 OCH 3 R' but species formed is unstable and dissociates under the reaction conditions to form a ketone

3. R MgX Grignard reagents react with esters C O – MgX + –– ++ R C O diethyl ether OCH 3 OCH 3 R' –CH 3 OMgX C O R R' This ketone then goes on to react with a second mole of the Grignard reagent to give a tertiary alcohol.

4. Example 2 CH 3 MgBr + (CH 3 ) 2 CHCOCH 3 O 1. diethyl ether 2. H 3 O + (CH 3 ) 2 CHCCH 3 OH CH 3 (73%) Two of the groups attached to the tertiary carbon come from the Grignard reagent.

5. 19.13 Reaction of Esters with Lithium Aluminum Hydride

6. Lithium aluminum hydride preferred for laboratory reductions. Sodium borohydride reduction is too slow to be useful. Catalytic hydrogenolysis used in industry but conditions difficult or dangerous to duplicate in the laboratory (special catalyst, high temperature, high pressure). Reduction of Esters Gives Primary Alcohols

7. Example: Reduction of an Ester 1. LiAlH 4 diethyl ether 2. H 2 O (90%) O COCH 2 CH 3 CH 3 CH 2 OH CH 2 OH +