Iridium/f-Amphox-Catalyzed Asymmetric Hydrogenation of Styrylglyoxylamides

Abstract

We report an iridium-catalyzed asymmetric hydrogenation reaction for the preparation of chiral homophenylalanine derivatives. Catalyzed by an iridium/f-amphox complex, the asymmetric hydrogenation of styrylglyoxylamides was conducted smoothly with turnover numbers of up to 10,000 and up to 98% ee. This method was successfully applied in a synthesis of a fragment of benazepril, a drug used for the treatment of high blood pressure.

Key words

homophenylalanines - asymmetric catalysis - iridium catalysis - hydrogenation - benazepril

• References and Notes

• 1 Parmley WW. Am. J. Med. 1998; 105: 27S
• 2a Hou FF, Zhang X, Zhang GH, Xie D, Chen PY, Zhang WR, Jiang JP, Liang M, Wang GB, Liu ZR, Geng RW. N. Engl. J. Med. 2006; 354: 131
• 2b Frampton JE, Peters DH. Drugs 1995; 49: 440
• 2c Chrysant SG, Chrysant GS. Expert Rev. Cardiovasc. Ther. 2003; 1: 345
• 2d Yasunari K, Maeda K, Nakamura M, Watanabe T, Yoshikawa J, Asada A. Cardiovasc. Drug Rev. 2004; 22: 189
• 2e McCormack PL, Keating GM. Drugs 2006; 66: 961
• 3 Ahmad AL, Oh PC, Abd Shukor SR. Biotechnol. Adv. 2009; 27: 286
• 4a Blaser H.-U, Jalett HP, Wiehl J. J. Mol. Catal. 1991; 68: 215
• 4b Blaser U.-H, Jalett H.-P, Spindler F. J. Mol. Catal. A: Chem. 1996; 107: 85
• 4c Blaser H.-U, Studer M. Acc. Chem. Res. 2007; 40: 1348
• 5 The Handbook of Homogeneous Hydrogenation . de Vries JG, Elsevier CJ. Wiley-VCH; Weinheim: 2008
• 6 Wu W, Liu S, Duan M, Tan X, Chen C, Xie Y, Lan Y, Dong X.-Q, Zhang X. Org. Lett. 2016; 18: 2938
• 7 Yu J, Long J, Yang Y, Wu W, Xue P, Chung LW, Dong X.-Q, Zhang X. Org. Lett. 2017; 19: 690
• 8 Yu J, Duan M, Wu W, Qi X, Xue P, Lan Y, Dong X.-Q, Zhang X. Chem. Eur. J. 2017; 23: 970
• 9 Zhao B, Han Z, Ding K. Angew. Chem. Int. Ed. 2013; 52: 4744
• 10 Denmark SE, Fan Y. J. Org. Chem. 2005; 70: 9667
• 11 CCDC 1862847 contains the supplementary crystallographic data for compound 2g. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
• 12 Thaper RK, Kumar Y, De S, Kumar DS. M. WO 02076375, 2002
• 13 Asymmetric Hydrogenation of Styrylglyoxylamides 1a–r; General ProcedureIn an argon-filled glove box, a 10 mL vial was charged with [Ir(COD)Cl]₂ (4.0 mg, 5.9 ×10^–3 mmol), f-amphox (7.3 mg, 13.1 × 10^–3 mmol), and anhyd i-PrOH (3 mL). The mixture was stirred for 2 h at 25 °C to give an orange-red solution. The resulting solution (50 μL, c = 4 × 10^–3 mmol/mL) and a solution of KOH in i-PrOH (40 μL, c = 0.05 mmol/mL) were transferred by a syringe into a 5 mL vial charged with the appropriate α-keto β-enamide (0.2 mmol) in DCE (2 mL). The vial was transferred to an autoclave, which was then charged with 20 atm of H₂ and the mixture was stirred at r.t. for 12 h. The hydrogen gas was released slowly in a well-ventilated hood, and the solution was passed through a short column of silica gel to remove the metal complex. The product was analyzed by ¹H NMR for conversion, and the ee was determined by HPLC.
• 14 (S,3E)-N-(tert-Butyl)-2-hydroxy-4-phenylbut-3-enamide (2c)White solid; yield: 46 mg (99%; conversion: 99%; 98% ee); mp 71–74 °C; [α]_D ²⁴ –7.8 (c 0.5, MeOH). HPLC: Chiracel AD-3 column [254 nm, 25 °C, hexane–i-PrOH (80:20); flow: 1.0 mL/min]; t _R ¹ = 4.0 min, t _R ² = 4.4 min. ¹H NMR (400 MHz, CDCl₃): δ = 7.36–7.29 (m, 2 H), 7.25 (dd, J = 9.9, 4.7 Hz, 2 H), 7.21–7.15 (m, 1 H), 6.65 (d, J = 15.9 Hz, 1 H), 6.18 (dd, J = 15.9, 7.0 Hz, 1 H), 5.97 (s, 1 H), 4.51 (d, J = 6.9 Hz, 1 H), 3.52 (s, 1 H), 1.29 (s, 9 H). ¹³C NMR (101 MHz, CDCl₃): δ = 171.5, 136.3, 132.6, 128.6, 128.0, 127.4, 126.8, 73.0, 51.4, 28.8. HRMS-ESI: m/z [M + Na]⁺ calcd for C₁₄H₁₉NNaO₂: 256.1305; Found: 256.1308.