Tropinone

tropinone is an alkaloid, synthesised in 1917 by Robert Robinson as a synthetic precursor to atropine, a scarce commodity during World War I ^[1] ^[2].

In organic chemistry the synthesis is considered a milestone in total synthesis. Tropinone is a complex bicyclic molecule but the reactants are fairly simple: succindialdehyde (see succinic acid and aldehydes), methyl amine and actone dicarboxylate (or even acetone). The synthesis is a good example of a biomimetic reaction or biogenetic-type synthesis because biosynthesis makes use of the same building blocks. It also demonstrates a tandem reaction is a one-pot synthesis.

[edit] Reaction mechanism

The main features apparent from the reaction sequence below are:

step 1: Nucleophilic addition of secondary amine to aldehyde followed by loss of water to create an imine
step 2: nucleophilic addition of the imine to the second aldehyde unit and first ring closure
step 3: intermolecular mannich reaction of the enolate of actone dicarboxylate
step 4: new enolate formation and new imine formation with loss of water for
step 5: second intramolecular mannich reaction and second ring closure
step 6: loss of 2 carboxylic groups to tropinone

A more detailed reaction mechanism is displayed below:

↑ R. Robinson, J. Chem. Soc. 1917, 111, 762 ± 768.
↑ The Art and Science of Total Synthesis at the Dawn of the Twenty-First Century K. C. Nicolaou, Dionisios Vourloumis, Nicolas Winssinger, and Phil S. Baran Angew. Chem. Int. Ed. 2000, 39, 44 ± 122