Kinetic Resolution of dl-Hydrobenzoins Catalyzed by Copper(II) Complexes of C2-Symmetric Thiophene-Derived Ligands
Woraluk Mansawat
a
Organic Synthesis Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Phayathai Road, Pathumwan, Bangkok 10330, Thailand
b
Institute of Organic Chemistry, University of Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany
,
Phanomsak Yukhet
a
Organic Synthesis Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Phayathai Road, Pathumwan, Bangkok 10330, Thailand
,
Worawan Bhanthumnavin
a
Organic Synthesis Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Phayathai Road, Pathumwan, Bangkok 10330, Thailand
a
Organic Synthesis Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Phayathai Road, Pathumwan, Bangkok 10330, Thailand
› Author AffiliationsFinancial support from the Thailand Research Fund through the Royal Golden Jubilee Ph.D. Program (Grant No. PhD/0206/2547 to W.M.) is acknowledged.
C2-Symmetrical chiral amino alcohol ligands with a central thiophene moiety were shown to be effective in combination with CuCl2 for the asymmetric acylation of dl-hydrobenzoins. In contrast to previously developed chiral ligands, readily available acetyl chloride and acetic anhydride can be used as reagents, in addition to benzoyl chloride, giving rise to the corresponding monoacylated products in up to 99% ee (S = 532).
Supporting Information
Supporting information for this article is available online at https://doi.org/10.1055/a-1815-7091.
31Ligands 1a–1l; General Procedure
A mixture of the appropriate chiral amino alcohol (1.0 or 2.0 mmol) and aldehyde (1.0 mmol) in EtOH (5 mL) was refluxed for 4 h. The mixture was cooled to 0 °C and NaBH4 (5.0 mmol) was added. When the amine had been consumed (TLC), the reaction was quenched with 10% aq HCl. The mixture was neutralized with sat. aq NaHCO3, then concentrated under reduced pressure. The residue was extracted with EtOAc and washed with H2O. The organic layer was dried (Na2SO4) and concentrated to give a crude product that was purified by flash column chromatography (silica gel, PE–EtOAc gradient).
(2R,2'R)-2,2'-[Thiene-2,5-diylbis(methyleneimino)]bis(2-phenylethanol) (1g)
Prepared according to the general method from thiophene-2,5-dicarbaldehyde (0.140 g, 1.0 mmol) and (R)-phenylglycinol (0.274 g, 2.0 mmol) as a white solid; yield: 0.325 g (85%); mp 103–105 °C; [α]D25 = –58.4 (c 1.0, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 7.41–7.28 (m, 10 H), 6.66 (s, 2 H), 3.89 and 3.73 (AB, J = 14.0 Hz, 2 × 2 H), 3.85 (ABX, JBX = 9.0, JAX = 4.2 Hz, 2 H), 3.69 (ABX, JAB = 10.9, JAX = 4.3 Hz, 2 H), 3.57 (ABX, JAB = 10.9, JBX = 8.9 Hz, 2 H), 2.72 (br s, 4 H). 13C NMR (101 MHz, CDCl3): δ = 142.8, 139.9, 128.8, 127.8, 127.4, 124.9, 66.7, 63.3, 45.9. HRMS (ESI+): m/z [M + H]+ calcd for C22H27N2O2S: 383.1793; found: 383.1809. Anal. Calcd for C22H26N2O2S: C, 69.08; H, 6.85; N, 7.32. Found: C, 69.16; H, 6.86; N, 7.38
32Screening of Catalytic Activities: General Procedure
The appropriate chiral ligand (0.025 mmol) and Cu(II) salt (0.025 mmol) were dissolved in CH2Cl2 (1.5 mL) and the mixture was stirred at rt for 2 h to afford a green homogeneous solution. The racemic 1,2-diol (0.25 mmol) and DIPEA (42.5 μL, 0.25 mmol) were added, and the mixture was cooled to 0 °C for 1 h. The appropriate acylating agent (0.125 mmol, 0.5 equiv) was added, and the mixture was stirred at 0 °C for 2 h then diluted with H2O and extracted with CH2Cl2 (×3). The combined organic layers were dried (MgSO4), concentrated under reduced pressure, and purified by chromatography (silica gel, PE–EtOAc). Enantioselectivities were determined by chiral HPLC (Chiralcel OJ-H® column, heptane–i-PrOH).
(1R,2R)-1,2-Bis(4-bromophenyl)-2-hydroxyethyl Acetate (5e)
White solid; yield: 44% (99% ee). HPLC [OD-H column, heptane–i-PrOH (9:1), λ = 215 nm, flow rate: 0.5 mL/min]: TR: 19.3 min (minor isomer); 23.9 min (major isomer). 1H NMR (300 MHz, CDCl3): δ = 7.42–7.33 (m, 4 H), 7.00–6.95 (m, 4 H), 5.72 (d, J = 7.5 Hz, 1 H), 4.85 (d, J = 7.5 Hz, 1 H), 2.62 (br s, 1 H), 2.12 (s, 3 H). 13C NMR (75 MHz, CDCl3): δ = 170.0, 137.7, 135.5, 131.5, 131.4, 129.0, 128.7, 122.5, 122.3, 79.2, 76.2, 21.1. HRMS (EI-MS): m/z [M+] calcd for C16H14Br2O3: 411.9310; found: 411.9314
