Convergent total synthesis of (±)-apomorphine hydrochloride was accomplished by an
approach that employs in the key step a sequence of transformations involving a [4+2]-cycloaddition
reaction followed by a hydrogen migration. Through this sequence of transformations,
the desired aporphine core was obtained regioselectively in 75% isolated yield. Since
only one regioisomer was produced in the key step of the synthesis, a polar [4+2]-cycloaddition
mechanism was proposed. Furthermore, NMR experiments and theoretical calculations
were carried out to elucidate the hydrogen migration mechanism. (±)-Apomorphine hydrochloride
was achieved after 9 steps in an overall yield of 8% involving benzyne chemistry.
Key words
(±)-apomorphine - aporphine core - benzyne chemistry - mechanisms - NMR experiments
- theoretical calculations
