The Preparation of Single Enantiomer 2-Naphthylalanine Derivatives Using Rhodium−Methyl BoPhoz-catalyzed Asymmetric Hydrogenation

Abstract

The single enantiomers of 2-naphthylalanine and N-tert-butoxycarbonyl 2-naphthylalanine were prepared from 2-naphthaldehyde. The sequence has been optimized and run on multikilogram scale, with the key step the asymmetric hydrogenation of methyl 2-acetamido-3-(2-naphthyl)propenoate using the rhodium complex of the methyl BoPhoz ligand, which proceeded smoothly at scale with 97.9% ee. Enhancement to >99.5% ee was achieved by crystallization of the methyl 2-amino-3-(2-naphthyl)propanoate methanesulfonic acid addition salt, the product of acidic deacylation of the hydrogenation product. This protocol for enantiomeric purity enhancement appears to be general for these types of amino acid derivatives. Subsequent transformations did not effect the enantiomeric purity, affording the desired products in >99.5% ee.

Recent Applications of Chiral Ferrocene Ligands in Asymmetric Catalysis

“…A comparative study on the hydrogenation of methyl 2‐acetamidocinnamate showed the superiority of the BoPhoz ligand 1 a over other well‐established ligands such as Chiraphos, Dipamp, or Josiphos. The same BoPhoz ligand 1 a has been efficiently applied to the synthesis of some nonnatural α‐amino acids, such as cyclopropylalanine52 (up to 98 % ee in the hydrogenation step) and 2‐naphtylalanine 53. In the latter case the asymmetric hydrogenation has been run on a multikilogram scale with an S/C ratio of 2000 and 97 % ee .…”

Chirale Ferrocenliganden in der asymmetrischen Katalyse

“…Eine vergleichende Studie der Hydrierung von Methyl‐2‐acetamidocinnamat bewies, dass der BoPhoz‐Ligand 1 a etablierten Liganden wie Chiraphos, Dipamp oder Josiphos überlegen ist. 1 a wurde auch zur Synthese einiger nichtnatürlicher α‐Aminosäuren wie Cyclopropylalanin52 (bis zu 98 % ee im Hydrierungsschritt) und 2‐Naphthylalanin eingesetzt 53. In letzterem Fall wurde die Hydrierung im Multikilogramm‐Maßstab mit einem S/C‐Verhältnis von 200 ausgeführt und verlief mit 97 % ee .…”

An enantioselective synthesis of a MEM-protected aetheramide A derivative

“…11 Asymmetric hydrogenation of 16 was carried out with chiral rhodium catalyst using conditions developed by Boaz et al to afford an optically active amino acid derivative. 12 Removal of the benzyl protecting group by catalytic hydrogenation furnished amino acid 18 in 75% yield (over two steps) with 98% ee . Deprotection of N -acetyl group of 18 by exposure to methanesulfonic acid followed by reaction of the resulting amine with benzylchloroformate resulted in Cbz-protection of amine as well as formation of O -carbobenzyloxy derivative.…”