Synthesis 2017; 49(16): 3546-3557
DOI: 10.1055/s-0036-1588855
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© Georg Thieme Verlag Stuttgart · New York

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

Ana Carolina A. Muraca
Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Rua Prof. Artur Riedel, 275, Diadema, SP 09972-270, Brazil   Email: raminelli@unifesp.br
,
Givago P. Perecim
Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Rua Prof. Artur Riedel, 275, Diadema, SP 09972-270, Brazil   Email: raminelli@unifesp.br
,
Alessandro Rodrigues
Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Rua Prof. Artur Riedel, 275, Diadema, SP 09972-270, Brazil   Email: raminelli@unifesp.br
,
Cristiano Raminelli*
Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Rua Prof. Artur Riedel, 275, Diadema, SP 09972-270, Brazil   Email: raminelli@unifesp.br
› Author Affiliations
We are grateful to São Paulo Research Foundation (FAPESP) for financial support (Grant No. 2015/09984-9). A.C.A.M thanks FAPESP and Coordination for the Improvement of Higher Education Personnel (CAPES) and G.P.P. thanks CAPES for their fellowships.
Further Information

Publication History

Received: 18 March 2017

Accepted after revision: 04 May 2017

Publication Date:
20 June 2017 (online)


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.

Supporting Information

 
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