Diastereoselective Synthesis of an Industrially Relevant 4-Aminopentanoic Acid by Asymmetric Catalytic Hydrogenation in a Biphasic­ System Using Aqueous Sodium Hydroxide as Substrate Phase

Dedicated to Prof. Dieter Enders on the occasion of his 70^th birthday, in deep respect for his groundbreaking contributions to asymmetric catalysis.

Abstract

A ’basic solution' for multiphase catalysis: The diastereoselective synthesis of a pharmaceutically relevant 4-aminopentanoic acid derivative has been studied using a chiral homogeneous catalyst in tailored biphasic reaction media. Different polar solvents were investigated as the stationary phase for the well-established Ru–Mandyphos catalyst in combination with aqueous NaOH as the substrate and product phase. Facile product isolation and effective recycling of the catalyst phase were demonstrated at gram-scale. In particular, up to 3200 turnovers have been achieved in seven repetitive batches with a diastereoselectivity of 87–96% using [EMIM][NTf₂]/NaOH_aq as the biphasic system.

Key words

asymmetric hydrogenation - aqueous biphasic catalysis - ruthenium - Mandyphos - ionic liquid - catalyst immobilization

• References

• 1 Keim W. Green Chem. 2003; 5: 105
• 2 Multiphase Homogeneous Catalysis . Cornils B, Herrmann WA, Horváth IT, Leitner W, Mecking S, Olivier-Bourbigou H, Vogt D. Wiley-VCH; Weinheim: 2005
• 3 Herrmann WA, Kohlpaintner CW. Angew. Chem., Int. Ed. Engl. 1993; 32: 1524
• 4 Aqueous-Phase Organometallic Catalysis: Concepts and Applications . 2nd ed.; Cornils B, Herrmann WA. Wiley-VCH; Weinheim: 2004
• 5 Prat D, Hayler J, Wells A. Green Chem. 2014; 16: 4546
• 6 Joó F, Kathó Á. Two-Phase Aqueous Hydrogenations . In Handbook of Homogeneous Hydrogenation . de Vries JG, Elsevier CJ. Wiley-VCH; Weinheim: 2008: 1327
• 7a Verspui G, Elbertse G, Sheldon FA, Hacking MA. P. J, Sheldon RA. Chem. Commun. 2000; 1363
• 7b McCarthy M, Stemmer H, Leitner W. Green Chem. 2002; 4: 501
• 8a Burgemeister K, Franciò G, Hugl H, Leitner W. Chem. Commun. 2005; 6026
• 8b Burgemeister K, Franciò G, Gego VH, Greiner L, Hugl H, Leitner W. Chem. Eur. J. 2007; 13: 2798
• 9 Pugin B, Studer M, Kuesters E, Sedelmeier G, Feng X. Adv. Synth. Catal. 2004; 346: 1481
• 10 von Lueder TG, Atar D, Krum H. Pharmacol. Ther. 2014; 144: 41
• 11 Hook D, Wietfeld B, Lotz M. WO 2008031567, 2008
• 12 Please note that the olefin moiety has a higher CIP priority as compared to the aryl substituent in (R)-1-CO₂H. After hydrogenation of the olefinic double bond, however, the priority sequence at C-4 reverses accordingly to the CIP rule. Thus the stereodescriptor for carbon 4 switches from (4R)-1-CO₂H to (4S)-2-CO₂H without the relative spatial orientation at the (preexisting) stereocenter being affected.
• 13a Perea JJ. A, Lotz M, Knochel P. Tetrahedron: Asymmetry 1999; 10: 375
• 13b Lotz M, Ireland T, Perea JJ. A, Knochel P. Tetrahedron: Asymmetry 1999; 10: 1839
• 14 Spindler F, Malan C, Lotz M, Kesselgruber M, Pittelkow U, Rivas-Nass A, Briel O, Blaser HU. Tetrahedron: Asymmetry 2004; 15: 2299
• 15 (2R,4S)-3-CO₂H =
• 16 For the isolation of pure (2R,4S)-2-CO₂H from a similar mixture, a reliable purification procedure through crystallyzation is reported: see ref. 11.
• 17 Huebner S, de Vries JG, Farina V. Adv. Synth. Catal. 2016; 358: 3