Cyclohexylamine → 1-Phenethylamine, (+)-

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Reaction Steps

3-Substituted 2-sulfonylmethylpropionic acids have been prepared in moderate e.e. (enantiomeric excess), i.e. up to around 80% e.e. in two steps, from the corresponding allyl sulfides, by sequential asymmetric hydrogenation and oxidation at sulfur (DE-A-4233100; Jendralla, Tetrahedron: Asymmetry (1994) 5:1183-1186; Beck et al, Tetrahedron (1994) 50:4691-4698; Jendrella, Proceedings of Chira Tech '97 (The Catalyst Group). The requisite allyl sulfides are normally prepared as E/Z mixtures by a Wittig olefination reaction; subsequent separation of geometric isomers is required to give optimum results in the asymmetric hydrogenation process. For example, (E)-2-tert-butylthiomethyl-3-(1-naphthyl)acrylic acid was hydrogenated in methanol using a catalyst prepared from (S)-(−)-BINAP, benzeneruthenium (II) chloride dimer and NaOAc at 150° C. and 13800 kPa (2000 psi), followed by peracid oxidation to give (S)-3-tert-butylsulfonyl-2-(1-naphthylmethyl)propionic acid. Similar results were achieved via hydrogenation of the corresponding cyclohexylamine salt form. To access (S)-3-tert-butylsulfonyl-2-(1-naphthylmethyl)propionic acid in >99% e.e. required additional processing, with concomitant loss of yield, by crystallisation of diastereomeric salts formed with (R)-1-phenylethylamine.

Provenance & Evidence