Synlett 2019; 30(01): 69-72
DOI: 10.1055/s-0037-1610351
letter
© Georg Thieme Verlag Stuttgart · New York

Enantioselective Synthesis of 1- and 4-Hydroxytetrahydrocarbazoles through Asymmetric Transfer Hydrogenation

Ömer Dilek
,
Süleyman Patir
,
Institute of Chemical Technology, TÜBITAK Marmara Research Center, 41470 Gebze, Kocaeli, Turkey   Email: erkan.erturk@tubitak.gov.tr
› Author Affiliations
Further Information

Publication History

Received: 22 October 2018

Accepted after revision: 16 November 2018

Publication Date:
04 December 2018 (online)

Abstract

Several 1- and 4-hydroxytetrahydrocarbazoles were prepared in high yields (up to 99%) and excellent enantiomeric excesses (up to >99% ee) from the corresponding 1- and 4-oxotetrahydrocarbazoles through asymmetric transfer hydrogenation by using the commercially available Noyori–Ikariya ruthenium catalyst. The immediate use of the freshly prepared catalyst and the use of a HCO2H–DABCO (11:6) mixture as the hydrogen source are crucial for achieving high activity and enantioselectivity. In this way, a tetrahydrocarbazole heterocycle fused to a lactone moiety was synthesized in 45% yield and 97% ee.

Supporting Information

 
  • References and Notes

  • 1 Knölker H.-J, Reddy KR. Chem. Rev. 2002; 102: 4303
  • 2 Schmidt AW, Reddy KR, Knölker H.-J. Chem. Rev. 2012; 112: 3193
  • 3 Bonjoch J, Solé D. Chem. Rev. 2000; 100: 3455
  • 4 Kuehne ME, Xu F. J. Org. Chem. 1998; 63: 9427
  • 5 Ohshima T, Xu Y, Takita R, Shibasaki M. Tetrahedron 2004; 60: 9569
  • 6 He W, Hu J, Wang P, Chen L, Ji K, Yang S, Li Y, Xie Z, Xie W. Angew. Chem. Int. Ed. 2018; 57: 3806
  • 7 Müller S, Webber MJ, List B. J. Am. Chem. Soc. 2011; 133: 18534
  • 8 Wang Y, Tu M.-S, Yin L, Sun M, Shi F. J. Org. Chem. 2015; 80: 3223
  • 9 Liu Q.-J, Yan W.-G, Wang L, Zhang XP, Tang Y. Org. Lett. 2015; 17: 4014
  • 10 Jaiswal PK, Biswas S, Singh S, Pathak B, Mobin SM, Samanta S. RSC Adv. 2013; 3: 10644
  • 11 Zhao F, Li N, Zhu Y.-F, Han Z.-Y. Org. Lett. 2016; 18: 1506
  • 12 Wu X, Zhu H.-J, Zhao S.-B, Chen S.-S, Luo Y.-F, Li Y.-G. Org. Lett. 2018; 20: 32
  • 13 Patir S, Ertürk E. J. Org. Chem. 2011; 76: 335
  • 14 Patir S, Ertürk E. Org. Biomol. Chem. 2013; 11: 2804
  • 15 Patir S, Tezeren MA, Salih B, Ertürk E. Synthesis 2016; 48: 4175
  • 16 Hillier MC, Marcoux J.-F, Zhao D, Grabowski EJ. J, McKeown AE, Tillyer RD. J. Org. Chem. 2005; 70: 8385
  • 17 Fujii A, Hashiguchi S, Uematsu N, Ikariya T, Noyori R. J. Am. Chem. Soc. 1996; 118: 2521
  • 18 Noyori R, Hashiguchi S. Acc. Chem. Res. 1997; 30: 97
  • 19 Corey EJ, Helal CJ. Angew. Chem. Int. Ed. 1998; 37: 1986
  • 20 Tietze LF, Kinzel T, Wolfram T. Chem. Eur. J. 2009; 15: 6199
  • 21 Noyori R, Yamakawa M, Hashiguchi S. J. Org. Chem. 2001; 66: 7931
  • 22 Oikawa Y, Yonemitsu O. J. Org. Chem. 1977; 42: 1213
  • 23 Uzgoren A, Uludag N, Okay G, Patir S. J. Heterocycl. Chem. 2009; 46: 1416
  • 24 Xu F, Zacuto MJ, Kohmura Y, Rosen J, Gibb A, Alam M, Scott J, Tschaen D. Org. Lett. 2014; 16: 5422
  • 25 Echeverria P.-G, Ayad T, Phansavath P, Ratovelomanana-Vidal V. Synthesis 2016; 48: 2523
  • 26 Peach P, Cross DJ, Kenny JA, Mann I, Houson I, Campbell L, Walsgrove T, Wills M. Tetrahedron 2006; 62: 1864
  • 27 Bromhead LJ, Visser J, McErlean CS. P. J. Org. Chem. 2014; 79: 1516
  • 28 Ikariya T, Hashiguchi S, Murata K, Noyori R. Org. Synth. Coll. Vol. XI . Wiley; London: 2009: 17
  • 29 (1S)-6-(Trifluoromethoxy)-2,3,4,9-tetrahydro-1H-carbazol-1-ol (3d); Typical ProcedureAn oven-dried 25 mL Schlenk tube A equipped with a magnetic stirrer bar was charged with catalyst 2 (12.7 mg, 20 μmol, 2 mol). The tube was capped with a glass stopper, evacuated for 15 min, and back-filled with N2. The glass stopper was then replaced with a rubber septum under a positive pressure of dry N2, and HCO2H/TEA (5:2) azeotropic mixture (1.1 mL) was added to the tube. In a separate oven-dried 10 mL Schlenk tube B, 6-(trifluoromethoxy)-2,3,4,9-tetrahydro-1H-carbazol-1-one (1d; 269 mg, 1.0 mmol) was dissolved in anhyd THF (5 mL) under N2, and the solution was transferred into Schlenk tube A by means of a cannula. The resulting mixture was stirred at 40 °C for 24 h under N2. THF was removed by rotary evaporation under reduced pressure, and the residue was treated with H2O (20 mL) and extracted with CH2Cl2 (3 × 30 mL). The combined organic phases were dried (Na2SO4), filtered, and concentrated by rotary evaporation in vacuo. Purification of the residue by flash column chromatography (silica gel) gave a pale-pink oil; yield: 271 mg (quant; 98% ee).TLC: Rf = 0.5 (silica gel; hexanes–EtOAc, 3:2). [α]D 23 +16 (c = 0.5, MeOH). HPLC: Chiralcel OD-H; hexane–i-PrOH (90:10), 1.0 mL/min; λ = 254 nm (UV/vis); t R = 8.8 min (3d), 10.8 min (ent-3d). FTIR (KBr): = 3415 (s), 2934 (m), 1870 (w), 1453 (m), 1213 (s), 1057 (m), 914 (m), 820 (m), 685 (m) cm−1. 1H NMR (600 MHz, DMSO): δ = 11.06 (s, 1 H), 7.36 (d, J = 8.7 Hz, 1 H), 7.32 (s, 1 H), 6.99 (dd, J = 8.7, 0.9 Hz, 1 H), 5.21 (d, J = 6.6 Hz, 1 H), 4.85–4.65 (m, 1 H), 2.66–2.58 (m, 1 H), 2.58–2.51 (m, 1 H), 2.04–1.92 (m, 2 H), 1.79–1.68 (m, 2 H). 13C NMR (APT, 150 MHz, DMSO): δ = [141.32, 141.31 (C, 3JC–F = 1.6 Hz)], 139.6 (C), 134.5 (C), 126.6 (C), [123.07, 121.38, 119.70, 118.02 (CF3, 1JC–F = 253.9 Hz)], 114.2 (CH), 112.0 (CH), 110.3 (CH), 110.1 (C), 62.5 (CH), 33.3 (CH2), 20.6 (CH2), 20.1 (CH2). 19F NMR (564 MHz, DMSO): δ = –56.9. HRMS (ESI): m/z [M − H2O + H]+ calcd for C13H11F3NO: 254.0787; found: 254.0781.