Total syntheses of lysicamine, (±)-nuciferine, (±)-nornuciferine, (±)-zanthoxyphylline iodide, (±)-Omethylisothebaine, and (±)-trimethoxynoraporphine were accomplished by an approach that involves the formation of aporphine cores through reactions between an isoquinoline derivative and silylaryl triflates promoted by CsF. Unprecedented formations of aporphine cores proceeded in good yields presumably through [4 + 2] cycloaddition reactions followed by hydrogen migrations.

A class of aryne precursors, that is, 2-(trimethylsilyl)aryl 4-chlorobenzenesulfonates, has been developed through well-established synthetic routes, which allow the formation of arynes under relatively mild conditions. All the aryne precursors were obtained from phenols and 4-chlorobenzenesulfonyl chloride, an inexpensive and easy-to-handle reagent with relatively low toxicity, and subjected to nucleophilic addition reactions, providing addition products in yields of 24 to 92%, and to cycloaddition reactions, affording cycloadducts in yields up to 80%. This work provides interesting insights into the mechanisms of aryne generation. In addition, 2-(trimethylsilyl)phenyl 4-chlorobenzenesulfonate was successfully employed in the total synthesis of (±)-aporphine.

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.