Science of Synthesis

Jautze, S.; Peters, R., Science of Synthesis: Stereoselective Synthesis, (2011) 3, 460.

The development of the catalytic enantioselective isomerization of achiral allylic amines ‌52‌ to form chiral enamines ‌53‌ is one of the most significant milestones in the field of asymmetric catalysis. This process is used for the industrial-scale isomerization of diethyl(geranyl)amine to produce (−)-menthol and other terpenes using a rhodium(I)/2,2′-bis(diphenylphosphino)-1,1′-binaphthyl catalyst.[‌43‌] The product is formed in high yield and in almost enantiopure form (‌Table 1‌, entry 2).[‌44‌] Interestingly, the reaction is relatively general, for example, secondary amines (entry 3) and substrates carrying aromatic (entry 5) or additional substituents (entries 1–4) can be utilized.[‌45‌] Spectroscopic and kinetic measurements, in combination with deuterium labeling experiments, reveal that the reaction proceeds via iminium formation through β-hydride elimination, and that this hydride is then transferred in an intramolecular fashion. Enantioselection is accomplished by an efficient differentiation of the enantiotopic C1 hydrogens.[‌46‌] Consequently, the reaction is stereospecific and requires geometrically pure starting materials for high enantiomeric excesses to be obtained. Enamines ‌53‌ with an E-configuration are formed regardless of the geometry of the starting allylic amine ‌52‌.

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References