Synthesis of Chiral Fluorides by Sequential Organocatalyzed Desymmetrization of Glutaric Anhydrides and Photoredox-Catalyzed Decarboxylic Fluorination

Abstract

We have developed an efficient method for the preparation of chiral fluorinated compounds by sequential organocatalyzed desymmetrization of 3-substituted glutaric anhydrides and photoredox-catalyzed decarboxylic fluorination. Chiral fluorides can be prepared in yields of up to 58% and with excellent enantioselectivities of up to 98% ee.

Key words

sequential catalysis - organocatalysis - photoredox catalysis - fluoro compounds - asymmetric catalysis - desymmetrization

• References and Notes

• 1a Wang J, Sánchez-Roselló M, Aceña JL, del Pozo C, Sorochinsky AE, Fustero S, Soloshonok VA, Liu H. Chem. Rev. 2014; 114: 2432
• 1b Mei H, Han J, Fustero S, Medio-Simon M, Sedgwick DM, Santi C, Ruzziconi R, Soloshonok VA. Chem. Eur. J. 2019; 25: 11797
• 1c Zhou Y, Wang J, Gu Z, Wang S, Zhu W, Aceña JL, Soloshonok VA, Izawa K, Liu H. Chem. Rev. 2016; 116: 422
• 2 Bégué J.-P, Bonnet-Delpon D, Croussea B, Legrosa J. Chem. Soc. Rev. 2005; 34: 562
• 3 Purser S, Moore PR, Swallow S, Gouverneur V. Chem. Soc. Rev. 2008; 37: 320

For reviews on asymmetric alcoholysis of cyclic anhydrides, see:
• 4a Atodiresei I, Schiffers I, Bolm C. Chem. Rev. 2007; 107: 5683
• 4b Chen Y, McDaid P, Deng L. Chem. Rev. 2003; 103: 2965
• 4c Spivey AC, Andrews BI. Angew. Chem. Int. Ed. 2001; 40: 3131
• 4d Rodriguez-Docampo Z, Connon SJ. ChemCatChem 2012; 4: 151
• 4e Díaz de Villegas MD, Gálvez JA, Etayo P, Badorrey R, López-Ram-de-Víu P. Chem. Soc. Rev. 2011; 40: 5564
• 5a Fryszkowska A, Komar M, Koszelewskia D, Ostaszewski R. Tetrahedron: Asymmetry 2005; 16: 2475
• 5b Peschiulli A, Gun’k Y, Connon SJ. J. Org. Chem. 2008; 73: 2454
• 5c Oh SH, Rho HS, Lee JW, Lee JE, Youk SH, Chin J, Song CE. Angew. Chem. Int. Ed. 2008; 47: 7872
• 5d Wang S.-X, Chen F.-E. Adv. Synth. Catal. 2009; 351: 547
• 5e Park SE, Nam EH, Jang HB, Oh JS, Some S, Lee YS, Song CE. Adv. Synth. Catal. 2010; 352: 2211
• 5f Yan L.-J, Wang H.-F, Chen W.-X, Tao Y, Jin K.-J, Chen F.-E. ChemCatChem 2016; 8: 2249

For reviews on decarboxylative reactions, see:
• 6a Dzik WI, Lange PP, Gooßen LJ. Chem. Sci. 2012; 3: 2671
• 6b Shang R, Liu L. Sci. China: Chem. 2011; 54: 1670
• 6c Weaver JD, Recio AIII, Grenning AJ, Tunge JA. Chem. Rev. 2011; 111: 1846
• 6d Rodríguez N, Gooßen LJ. Chem. Soc. Rev. 2011; 40: 5030
• 6e Gooßen LJ, Rodríguez N, Gooßen K. Angew. Chem. Int. Ed. 2008; 47: 3100
• 7 Ventre S, Petronijevic FR, MacMillan DW. C. J. Am. Chem. Soc. 2015; 137: 5654
• 8 Leung JC. T, Sammis GM. Eur. J. Org. Chem. 2015; 2197
• 9 Rueda-Becerril M, Mahé O, Drouin M, Majewski MB, West JG, Wolf MO, Sammis GM, Paquin J.-F. J. Am. Chem. Soc. 2014; 136: 2637
• 10 Wu X, Meng C, Yuan X, Qian X, Jia X, Ye J. Chem. Commun. 2015; 51: 11864
• 11 Chen D.-F, Han ZY, Zhou X.-L, Gong L.-Z. Acc. Chem. Res. 2014; 47: 2365
• 12 Alkyl 3-Aryl-4-fluorobutanoates 3; General Procedure MTBE (15 mL) was added to a mixture of the appropriate 3-arylglutaric anhydride 1 (0.5 mmol) and catalyst A4 (0.05 mmol), and the mixture was stirred at –20 °C for 30 min. MeOH (5 mmol) was added, and stirring was continued at –20 °C for 24 h. When the reaction was complete, the solvent was evaporated under reduced pressure without further purification. The residue was dissolved in 1:1 MeCN–H₂O (5.0 mL) and Ir(ppy)₂(dtbbpy)PF₆ (I) (0.010 mmol, 2 mol%), Selectfluor (1.5 mmol), and Na₂HPO₄ (1 mmol) were added. The mixture was irradiated by 40 W (456 nm) blue LEDs for 12 h at 25 °C under N₂ until the reaction was complete. The reaction was then quenched with aq NaCl, the mixture was extracted with Et₂O, and the extracts were purified by preparative TLC.
• 13 Methyl (R)-4-Fluoro-3-phenylbutanoate (3a) Purified by preparative TLC (PE–EtOAc, 10:1) to give a white oil; yield: 56.8 mg (58%, ee 92%); [α]_D ²⁰ = –37.9 (c 2.15, CHCl₃). HPLC [Daicel Chiralpak OD-H, hexane–i-PrOH (98:2), flow rate: 1.0 mL/min, T = 25 °C, λ = 220 nm]: t _R = 8.292 min (major), t _R = 14.765 min (minor). ¹H NMR (400 MHz, CDCl₃): δ = 7.36–7.29 (m, 2 H), 7.28–7.22 (m, 3 H), 4.68–4.41 (m, 2 H), 3.62 (s, 3 H), 3.59–3.46 (m, 1 H), 2.89 (dd, J = 16.0, 6.9 Hz, 1 H), 2.70 (dd, J = 16.0, 8.0 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 172.2, 139.5, 128.7, 127.8, 127.4, 86.1 (J = 173.0 Hz), 51.7, 42.6, 36.3. ¹⁹F NMR (376 MHz, CDCl₃): δ = –219.8. ESI (FTMS): m/z [M + Na]⁺ calcd for C₁₁H₁₃FNaO₂: 219.0798; found: 219.0801.