Science of Synthesis

Wolkenberg, S. E.; Garbaccio, R. M., Science of Synthesis, (2007) 20, 411.

A method for the asymmetric synthesis of α-amino acids from α-oxo acids has been developed,[‌94‌,‌95‌] based on N-aminodihydroindoles ‌75‌ as chiral auxiliaries. Two-step condensation–cyclization of ‌75‌ with an oxo acid produces hydrazono lactones ‌76‌ in good yields (‌Scheme 23‌). Extensive experimentation has identified aluminum/mercury amalgam as the best reductant for the enantiospecific reduction to the hydrazono lactones ‌77‌. It has been found that inclusion of a methyl group at either R1 or R2 enhances the enantioselectivity versus unsubstituted methylene and that the reduction gives the same antipode in either case. Hydrolysis of the ester in hydrochloric acid/dioxane followed directly by hydrogenation of the N—N bond produces amino acids ‌78‌ in good yield without stereochemical erosion and allows for recovery of the valuable chiral auxiliary.

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References

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• 8.Meeeee-Meee, (8888) M 88e, 8888.