Convergent Total Synthesis of (+/-)-Apomorphine via Benzyne Chemistry: Insights into the Mechanisms Involved in the Key Step

Author(s)

Muraca, Ana Carolina A. ; Perecim, Givago P. ; Rodrigues, Alessandro ; Raminelli, Cristiano

• Document type: Journal article
• Source: SYNTHESIS-STUTTGART; v. 49, n. 16, p. 3546-3557, AUG 2017.
• Web of Science Citations: 4

Abstract

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. (AU)

• FAPESP's process: 15/09984-9 - Development of new routes for preparation of aryne precursors with application in stereoselective syntheses of bioactive alkaloids
• Grantee: Cristiano Raminelli
• Support Opportunities: Regular Research Grants