Synfacts 2021; 17(05): 0577
DOI: 10.1055/s-0040-1719805
Chemistry in Medicine and Biology

The First Total Synthesis of Cocaine

Dirk Trauner
Matthew McLarney DiCairano
Willstätter R, *, Bode A. Ludwig Maximilian University of Munich, Germany
Ueberführung von Tropinon in r-Cocaïn.

Chem. Ber. 1901;
34: 1457-1461
DOI: 10.1002/cber.19010340220.


In 1901, Richard Willstätter and ­Adolf Bode reported one of the first vollständige Synthese (complete or total synthesis) of a complex natural product. In this seminal work, the authors began their synthesis from cycloheptanone and, in 23 linear steps, completed the synthesis of (±)-cocaine. The key step is a bromination followed by an intramolecular transannular SN2 to form the tropane skeleton (Chem. Ber. 1901, 34, 129).



Cycloheptanone was elaborated to allylic bromide A, which was reductively aminated to afford the precursor B to the tropane skeleton. The key intramolecular transannular SN2 reaction was achieved upon exposure to Br2 and the resulting salt C was further manipulated to complete the synthesis of tropinone. Finally, an α-carboxylation, dissolving metal reduction, Fischer esterification, and a benzoylation afforded (±)-cocaine, to complete one of the first examples of a total synthesis.


Publication History

Publication Date:
20 April 2021 (online)

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