Coniine is a toxic compound found in the plant hemlock (conium maculatum), with which the ancient Gr — Physical Chemistry — Kinetics Chemistry Question
Chemical Structure and Absolute Stereochemistry of Coniine
Coniine is a toxic compound found in the plant hemlock (conium maculatum), with which the ancient Greek philosopher Socrates was poisoned. Coniine is a nitrogenous compound belonging to the alkaloid family.
Find the chemical structure and absolute stereochemistry of coniine by completing the following series of reactions. Also, draw the structures of the intermediates A, B, and C.
[VISUAL]
Model Answer
Coniine is (S-2-propylpiperidine.
Intermediate A is (S-N,N-dimethyloct-7-en-4-amine (optically active, C10H21N).
Intermediate B is (S)-benzyl 2-propylpiperidine-1-carboxylate (Z-protected coniine).
Intermediate C is (S-5-(((benzyloxy)carbonyl)amino)octanoic acid.
Reaction steps:
1) Coniine is subjected to Hofmann exhaustive methylation (1. CH3I, 2. Ag2O, H2O, delta) to yield Intermediate A. Repeating this Hofmann elimination on A yields a mixture of 1,4-octadiene and 1,5-octadiene.
2) Coniine is reacted with benzyl chloroformate (C6H5CH2OCOCl, Z-Cl) in NaOH at 0 °C to yield Intermediate B (Z-protected coniine). B is oxidized with KMnO4 and heat (delta) to yield Intermediate C. Hydrogenolysis of C over Pd/C (H2/Pd/C) removes the Z protecting group to yield (S-5-aminooctanoic acid.
The KMnO4 oxidation reaction step is based on A. M. Castano, J. M. Cuerva, A.M Echawarren, Tetrahedron Letters, 35, 7435–7438 (1994).