Q12P - Organic Chemistry (Mcmurry)

Question

How would you carry out the following transformation, a step used in the commercial synthesis of (S)-ibuprofen?

Step-by-Step Solution

Answer

The transformation occurs in the commercial synthesis of (S)-ibuprofen is,

Step 1: Conversion of alcohols into Tosylates

The ${\mathbf{S}}_N\mathbf{2}$ reaction of alcohol via a tosylate occurs with only one inversion, and the stereochemistry of the product has the opposite stereochemistry to the starting alcohol compound.

Step 2: The commercial synthesis of (S)-ibuprofen

We know that the reactions which run under ${\text{S}}_{\text{N}}\text{2}$ conditions have OH as a poor leaving group. The p-TosCl is an excellent leaving group, and the reaction of toluenesulfonate of alcohol with ${\text{CN}}^{\text{-}}$ occurs rapidly under ${\text{S}}_{\text{N}}\text{2}$ conditions. This gives the desired product with the inversion of configuration at the chiral carbon.

Synthesis of (S)-ibuprofen