Acylative and Silylative Dynamic Kinetic Resolutions of 6-Hydroxy-2H-pyran-3(6H)-one Catalyzed by Chiral Guanidines

Abstract

Chiral guanidine-catalyzed acylative and silylative dynamic kinetic resolutions of 6-hydroxy-2H-pyran-3(6H)-one were achieved. We succeeded in developing a non-enzymatic acylative dynamic kinetic resolution of 6-hydroxy-2H-pyran-3(6H)-one with high enantioselectivity, which could be improved by recrystallization. In contrast, the non-enzymatic silylative dynamic kinetic resolution of 6-hydroxy-2H-pyran-3(6H)-one was accomplished with a moderate selectivity for the first time.

Key words

acylation - guanidines - dynamic kinetic resolution - organocatalysis - silylation - hydroxypyranone

Publication History

Received: 17 October 2023

Accepted after revision: 08 November 2023

Accepted Manuscript online:
08 November 2023

Article published online:
14 December 2023

• References and Notes

• 1 Achmatowicz OJr, Bukowski P, Szechner B, Zwierzchowska Z, Zamojski A. Tetrahedron 1971; 27: 1973
• 2 Guo H, O’Doherty GA. Org. Lett. 2006; 8: 1609

For reviews, see:
• 3a Class YJ, DeShong P. Chem. Rev. 1995; 95: 1843
• 3b Ylijoki KE. O, Stryker JM. Chem. Rev. 2013; 113: 2244
• 3c Palframan MJ, Pattenden G. Chem. Commun. 2014; 50: 7223
• 3d Ghosh AK, Brindisi M. RSC Adv. 2016; 6: 111564
• 3e Mahajan PS, Humne VT, Mhaske SB. Curr. Org. Chem. 2017; 21: 503
• 3f Song W, Wang S, Tang W. Chem. Asian J. 2017; 12: 1027
• 3g Makarov AS, Uchuskin MG, Trushkov IV. Synthesis 2018; 50: 3059
• 3h Liang L, Guo L.-D, Tong R. Acc. Chem. Res. 2022; 55: 2326
• 4 Benkovics T, Ortiz A, Guo Z, Goswami A, Deshpande P. Org. Synth. 2014; 91: 293
• 5 Shimokawa J, Harada T, Yokoshima S, Fukuyama T. J. Am. Chem. Soc. 2011; 133: 17634
• 6 Ortiz A, Benkovics T, Beutner GL, Shi Z, Bultman M, Nye J, Sfouggatakis C, Kronenthal DR. Angew. Chem. Int. Ed. 2015; 54: 7185
• 7 Zhao C, Li F, Wang J. Angew. Chem. Int. Ed. 2016; 55: 1820
• 8 Sugawara K, Imanishi Y, Hashiyama T. Tetrahedron: Asymmetry 2000; 11: 4529
• 9a Isobe T, Fukuda K, Araki Y, Ishikawa T. Chem. Commun. 2001; 243
• 9b Ishikawa T, Isobe T. Chem. Eur. J. 2002; 8: 552

For reviews, see:
• 10a Rendler S, Oestreich M. Angew. Chem. Int. Ed. 2008; 47: 248
• 10b Weickgenannt A, Mewald M, Oestreich M. Org. Biomol. Chem. 2010; 8: 1497
• 10c Xu L.-W, Chen Y, Lu X. Angew. Chem. Int. Ed. 2015; 54: 9456
• 10d Seliger J, Oestreich M. Chem. Eur. J. 2019; 25: 9358
• 11 Hoveyda AH, Snapper ML. In Organosilicon Chemistry: Novel Approaches and Reactions, Chap. 13. Hiyama T, Oestreich M. Wiley-VCH; Weinheim: 2020: 459
• 12 Seliger J, Oestreich M. Angew. Chem. Int. Ed. 2021; 60: 247
• 13 Dong X, Weickgenannt A, Oestreich M. Nat. Commun. 2017; 8: 15547
• 14a Baratta W, Chelucci G, Gladiali S, Siega K, Toniutti M, Zanette M, Zangrando E, Rigo P. Angew. Chem. Int. Ed. 2005; 44: 6214
• 14b Baratta W, Ballico M, Chelucci G, Siega K, Rigo P. Angew. Chem. Int. Ed. 2008; 47: 4362
• 14c Bertoli M, Choualeb A, Lough AJ, Moore B, Spasyuk D, Gusev DG. Organometallics 2011; 30: 3479
• 15a Nakata K, Shiina I. Org. Biomol. Chem. 2011; 9: 7092
• 15b Yamada A, Nakata K, Shiina I. Tetrahedron: Asymmetry 2017; 28: 516
• 16a Yoshimatsu S, Yamada A, Nakata K. J. Org. Chem. 2018; 83: 452
• 16b Yoshimatsu S, Nakata K. Adv. Synth. Catal. 2019; 361: 4679
• 16c Suzuki T, Iwakura M, Nakata K. ChemistrySelect 2021; 6: 11261
• 16d Miyazaki K, Nakata K. J. Org. Chem. 2022; 87: 10509
• 16e Manaya I, Ikeue T, Nakata K. ChemistrySelect 2022; 7: e202202511
• 17 When using Ph₂MeSiCl, the yield of 1 was 7% with 71% ee; when using PhMe₂SiCl, the yield of 1 was 25% with 41% ee; and when using TBSCl, no reaction occurred.
• 18 Acylative Dynamic Kinetic Resolution of Lactol 1; Typical Procedure (Table [2], Entry 5) Catalyst C (3.1 mg, 9.9 μmol) and cyclohexanecarboxylic anhydride (54.5 μL, 0.24 mmol) were added successively to a solution of lactol 1 (22.8 mg, 0.20 mmol) in Et₂O (1.0 mL) at r.t., and the mixture was stirred for 24 h. The reaction was then quenched with sat. aq NaHCO₃ at 0 °C. The organic layer was separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na₂SO₄), filtered, and concentrated, and the resulting residue was purified by column chromatography [silica gel, hexane–EtOAc (9:1)] to give (R)-7 as a colorless oil; yield: 38.1 mg (85%, 94% ee). 1 mmol Scale Acylative Dynamic Kinetic Resolution of Lactol 1 (Table [2], Entry 6) The above procedure was followed using lactol 1 (114.2 mg, 1.00 mmol) in Et₂O (5.0 mL) with catalyst C (15.7 mg, 0.05 mmol) and cyclohexanecarboxylic anhydride (272.4 μL, 1.20 mmol) to give (R)-7 as a pale-yellow oil; yield: 211.2 mg (94% yield, 94% ee). Recrystallization of Acylate (R)-7 (Table [2], entry 6) The oily acylate product (R)-7 (127.2 mg, 97:3 er) was stored in a refrigerator (4 °C) overnight to give crystals that were recrystallized from hexane with a small amount of CH₂Cl₂ to afford a white solid; yield: 66.2 mg (52% recovered yield, >98.5:1.5 er); mp 58–60 °C. Silylative Dynamic Kinetic Resolution of Lactol 1; Typical Procedure (Table [3], Entry 7) Catalyst B (3.9 mg, 10.0 μmol) and i-Pr₂NEt (51.3 μL, 0.30 mmol) were successively added to a solution of lactol 1 (22.8 mg, 0.20 mmol) in toluene (4.0 mL) at r.t., and the mixture was cooled to 0 °C. A 0.20 mM solution of Ph₃SiCl in toluene (1.50 mL, 0.30 mmol) was slowly added to the mixture over 15 h by using a syringe pump. The reaction was additionally stirred for 7 h at 0 °C, and then the reaction was quenched with sat. aq NaHCO₃ at 0 °C. The organic layer was separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na₂SO₄), filtered, and concentrated to give a residue that was purified by column chromatography [silica gel, toluene–EtOAc (100:1)] to give (S)-8 as a colorless oil; 88% NMR yield (59% ee). 1 mmol Scale Silylative Dynamic Kinetic Resolution of Lactol 1 (Table [3], entry 8) The above procedure was followed using lactol 1 (114.1 mg, 1.00 mmol) in toluene (20 mL), catalyst B (19.4 mg, 0.05 mmol), and i-Pr₂NEt (256.4 μL, 1.50 mmol), with slow addition (15 h) of a 0.20 mM solution of Ph₃SiCl in toluene (7.50 mL, 1.50 mmol). The product was purified by flash column chromatography [silica gel, toluene to toluene–EtOAc (99:1)] to give (S)-8 as a white solid: 348.0 mg (93%, 47% ee).