Job/Unit: O40045
/KAP1
Date: 30-04-14 16:45:13
Pages: 7
A Recyclable Organocatalyst of the Asymmetric Michael Reaction
+
1.09 mmol) in water (8 mL) was added to a stirred solution of 5-
Br (0.73 g, 0.95 mmol) in the same solvent (12 mL) at ambient tem-
perature. The precipitate was filtered off, washed with water (2ϫ
10 mL) and dried in vacuo (0.5 Torr) at 50 °C for 2 h to afford 5-
PF6 (0.62 g, 88%) as a colorless solid. M.p. 124 °C. [α]2D0 = +2.6 (c
26.3, 26.1, 26.00 ppm. HRMS (ESI): calcd. for C19H23O4 [M +
H]+ 315.1591; found 315.1595 and for C19H22O4Na+ [M + Na]+
337.1410; found 337.1404.
(S)-3-[1-(Ferrocenyl)-3-oxo]-4-hydroxy-2H-chromen-2-one (8f): Yel-
low solid (29.1 mg, 70%). M.p. 104 °C (dec.). 51% ee; the ee value
of the product was determined by HPLC by using an AD-H col-
umn (n-hexane/iPrOH = 99:1), flow rate 0.7 mL/min–1, λ = 254 nm,
tR = 9.19 (minor), 13.08 (major) min. [α]2D5 = +23.20 (c = 1.0,
MeOH). 1H NMR (CDCl3): δ = 9.27 (m, 0.3 H), 7.88 (m, 1 H),
7.48 (m, 2 H), 7.25 (m, 2 H), 4.49–3.92 (m, 11 H), 3.40 (m, 1 H),
2.41–1.94 (m, 4 H), 1.64 (m, 2 H), 1.26 (m, 3 H) ppm. 13C NMR
(CDCl3): δ = 212.8, 160.3, 131.7, 123.9, 116.5, 116.2, 107.9, 88.6,
69.8–67.3 (9 C), 46.9, 28.2–31.3 (3 C) ppm. HRMS (ESI): calcd.
for C23H20O4Fe+ [M + H]+ 416.0706; found 416.0702.
1
= 1, MeOH). H NMR ([D6]DMSO): δ = 9.10–9.04 (s, 1 H), 8.30
(m, 1 H), 7.94–7.58 (m, 3 H), 7.55–7.02 (m, 20 H), 5.31 (m, 1 H),
5.08 (m, 4 H), 4.99–4.94 (m, 1 H), 4.33–4.15 (m, 2 H), 4.13–3.83
(m, 2 H), 2.45–2.30 (m, 4 H), 2.07 (m, 2 H), 2.06–1.51 (m, 8 H)
ppm. 13C NMR ([D6]DMSO): δ = 172.3, 170.9, 155.6, 140.7, 138.4,
136.9, 135.8, 127.9, 125.5–121.1 (Ar), 65.3, 59.0, 56.6, 48.5, 39.7,
39.5, 34.4, 33.1, 32.6, 31.8, 28.6, 24.4, 21.6, 20.9 ppm. HRMS:
calcd. for C42H47N4O5 [M]+ 687.3541; found 687.3548.
+
3-{5-[(1S,2S)-2-Amino-1,2-diphenylethylamino]-5-oxopentyl}-1-(4-
carboxybutyl)-1H-imidazol-3-ium Hexafluorophosphate(V) (3): A
mixture of 5% Pd/C (50 mg), 5-PF6 (0.61 g, 0.82 mmol) and MeOH
(10 mL) was stirred under H2 (1 bar) at ambient temperature for
24 h. The catalyst was filtered off and washed with MeOH (10 mL).
The combined filtrate and washings were concentrated under re-
duced pressure (10 Torr), and the residue was dried in vacuo
(0.5 Torr) at 50 °C for 2 h to afford 3 (0.48 g, 96%) as a colorless
(S)-3-[1-(Cymantrenyl)-3-oxo]-4-hydroxy-2H-chromen-2-one (8g):
Yellow solid (30.5 mg, 70%). M.p. 110 °C (dec.). 72% ee; the ee
value of the product was determined by HPLC by using an AD-H
column (n-hexane/iPrOH = 7:3), flow rate 0.7 mL/min–1, λ =
220 nm, tR = 5.99 (minor), 7.80 (major) min. [α]2D5 = +18.47 (c =
1
1.0, MeOH). H NMR (CDCl3): δ = 9.60 (m, 1 H), 7.96 (m, 1 H),
7.79 (m, 1 H), 7.52 (m, 2 H), 7.28 (m, 4 H), 5.30 (m, 1 H), 5.07
(m, 1 H), 4.80–4.46 (m, 5 H), 4.29–4.07 (m, 2 H), 3.89–3.53 (m, 2
H), 3.26–2.96 (m, 2 H), 2.52–2.12 (m, 5 H), 2.09–1.68 (m, 4 H),
1.43–1.13 (m, 3 H) ppm. 13C NMR ([D6]DMSO): δ = 215.8 (4 C),
162.9, 142.3, 134.2, 126.8, 96.7, 90.5, 90.0, 53.2 ppm. HRMS (ESI):
calcd. for C21H15MnO7Na+ [M + Na]+ 457.0090; found 457.0039.
solid. M.p. 103–105 °C. [α]2D0 = –24.58 (c = 1, MeOH). H NMR
1
([D6]DMSO): δ = 9.16 (s, 1 H), 8.45 (d, J = 8.1 Hz, 1 H, NH), 7.80
(d, J = 19.4 Hz, 2 H, CH), 7.31–7.07 (m, 10 H), 5.00 (t, J = 8.1 Hz,
1 H, CH), 4.29–3.81 (m, 5 H, CH2, CH), 2.28–1.86 (m, 4 H, CH2),
1.80–1.36 (m, 8 H, CH2) ppm. 13C NMR ([D6]DMSO): δ = 174.6,
171.3, 141.7, 135.9, 128.9–126.5 (Ar), 122.4, 71.3, 59.3, 58.6, 48.6,
34.3, 33.3, 28.9, 26.6, 25.3, 22.3, 21.3 ppm. HRMS: calcd. for
Catalyst Recovery: The catalyst that had remained after extraction
of product 8 with Et2O was dried under reduced pressure (1.0 Torr)
for 30 min; fresh portions of 6 (16.2 mg, 0.10 mmol), 7a (17.5 mg,
0.12 mmol), AcOH (30 μL) and THF (150 μL) were added, and the
reaction was performed at ambient temperature for 24 h.
+
C27H35N4O3 [M]+ 463.2700; found 463.2704.
General Procedure for the Michael Reaction: A mixture of 4-hy-
droxy-2H-chromen-2-one (6; 16.2 mg, 0.1 mmol), α,β-unsaturated
ketone 7 (0.12 mmol), catalyst 3 (12.2 mg, 0.02 mmol), AcOH
(30 μL) and THF (150 μL) was stirred at ambient temperature for
the period specified in Tables 1 and 2. After the reaction was com-
plete (TLC monitoring), the solvent and AcOH were removed un-
der reduced pressure, and the residue was extracted with Et2O (5ϫ
10 mL). The combined extracts were concentrated under reduced
pressure (10 Torr), and products 8 were purified by column
chromatography (silica gel; eluent n-hexane/EtOAc = 3:1, then
EtOAc). Analytical data for new compounds 8c–g are given below.
Supporting Information (see footnote on the first page of this arti-
cle): Procedures for the preparation of each compound; 1H, 13C
NMR and HR mass spectra as well as HPLC data.
Acknowledgments
Financial support by the Russian Academy of Sciences (Basic Re-
search Program No. 1 of the Department of Chemistry and Mate-
rial Sciences) and by the Russian Foundation of Basic Research
(Project 12-03-00420) are gratefully acknowledged.
(S)-4-Hydroxy-3-[3-oxo-1-(pyridin-3-yl)butyl]-2H-chromen-2-one
(8c): Colorless solid (29.9 mg, 97%). M.p. 193–195 °C. 70% ee; the
ee value of the product was determined by HPLC by using an AD-
H column (n-hexane/iPrOH = 7:3), flow rate 0.7 mL/min–1, λ =
254 nm, tR = 6.35 (minor), 8.38 (major) min. [α]2D5 = +1.55 (c =
[1] a) Science of Synthesis: Asymmetric Organocatalysis (Eds.: B.
List, K. Maruoka), Thieme, Stuttgart, 2012; b) Comprehensive
Enantioselective Organocatalysis: Catalysts, Reactions, and Ap-
plications (Ed.: P. I. Dalco), Wiley-VCH, Weinheim, 2013; c) H.
Pellissier, Recent Developments in Asymmetric Organocatalysis,
RSC Publishing, Cambridge, 2010.
[2] a) E. Marqués-López, R. P. Herrera, M. Christmann, Nat.
Prod. Rep. 2010, 27, 1138–1167; b) P. Melchiorre, M. Marigo,
A. Carlone, G. Bartoli, Angew. Chem. Int. Ed. 2008, 47, 6138–
6171; Angew. Chem. 2008, 120, 6232–6265; c) M. Rueping, J.
Dufour, F. R. Schoepke, Green Chem. 2011, 13, 1084–1105.
[3] a) U. Eder, R. Wiechert, G. Sauer. Germ. Pat. DE 2014757,
1971; b) Z. G. Hajos, D. R. Perrish. Germ. Pat. DE 2102623,
1971; c) X. Huang, S. Broadbent, C. Dvorak, S.-H. Zhao, Org.
Process Res. Dev. 2010, 14, 612–616; d) K. M. Belyk, B. Xiang,
P. G. Bulger, W. R. Leonand, J. Balsells, J. Yin, C.-Y. Chen,
Org. Process Res. Dev. 2010, 14, 692–700; e) D. E. Patterson,
S. Xie, L. A. Jones, M. H. Osterhout, C. G. Henry, T. D. Roper,
Org. Process Res. Dev. 2007, 11, 624–627; f) T. Ikemoto, Y.
Watanabe, US Pat. 2009176199, 2009.
1
1.0, CH2Cl2). H NMR ([D6]DMSO): δ = 8.50 (m, 1 H), 8.39 (m,
1 H), 7.85 (m, 1 H), 7.64 (m, 2 H), 7.50–7.19 (m, 4 H), 4.06 (m, 1
H), 2.34 (m, 1 H), 1.96 (s, 1 H), 1.67–1.61 (s, 2 H) ppm. 13C NMR
([D6]DMSO): δ = 211.2, 152.4, 148.7–146.7 (2 C), 139.5, 135.0,
131.9, 123.9–122.9 (3 C), 116.2, 102.7–100.4 (2 C), 42.4, 32.9, 30.6,
+
27.3 ppm. HRMS (ESI): calcd. for C18H16NO4 [M + H]+
310.1074; found 310.1088.
(S)-3-(1-Cyclohexyl-3-oxobutyl)-4-hydroxy-2H-chromen-2-one (8e):
Colorless solid (23.5 mg, 75 %). M.p. 63–64 °C. 90% ee; the ee
value of the product was determined by HPLC by using an AD-H
column (n-hexane/iPrOH = 7:3), flow rate 0.7 mL/min–1, λ =
220 nm, tR = 7.32 (major), 5.83 (minor) min. [α]2D5 = –61.07 (c =
1
1.0, MeOH). H NMR (CDCl3): δ = 7.93 (m, 1 H), 7.48 (m, 1 H),
7.26 (m, 2 H), 3.36–3.17 (m, 1 H), 3.09–2.74 (m, 2 H), 2.28–2.10
(m, 4 H), 1.95–1.83 (m, 1 H), 1.82–1.44 (m, 7 H), 1.37–1.07 (m, 6
H) ppm. 13C NMR (CDCl3): δ = 214.4, 161.7, 152.7, 131.5, 123.9,
116.7–116.1 (2 C), 107.3, 44.9, 36.9, 36.1, 32.9, 32.0, 31.8, 29.9,
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5