Total Synthesis of (±)-Kainic Acid with an Aza-[2,3]-Wittig Sigmatropic Rearrangement as the Key Stereochemical Determining Step.

A flexible route to the kainoid skeleton is exemplified by the synthesis of (±)-kainic acid from 3-butyn-1-ol. The route relies on the aza-[2,3]-Wittig sigmatropic rearrangement to efficiently install the relative stereochemistry between C2-C3. The C4 stereocenter was derived from a diastereocontrolled iodolactonization. The aza-[2,3]-Wittig rearrangement potentially allows structural diversity at C3 and the displacement of the tosyloxy group with retention of stereochemistry allows structural diversity at C4. The trans-C2 carboxylic acid functional group was found to be the most important for retention of stereochemistry at C4 upon treatment with a higher order cyano cuprate reagent. [ABSTRACT FROM AUTHOR]