244
STOCKINGER AND TRAPP
J = 16.78 Hz, J = 2.82Hz, -COCH2-) ppm. 13C-NMR (125.77MHz, CDCl3):
δ = 192.33, 163.35, 137.95, 129.09, 129.00, 126.24, 107.52, 81.24, 43.53ppm.
ATR-FTIR: υ = 3031, 1670, 1592, 1267, 1226, 1037, 932, 756cm-1. HR-MS
(EI+, m/z): calc. for C11H10O2 [M]: 174.0681, found: 174.0672.
material, but to create rapid screening platforms,34 where cat-
alysts are prepared by complexing metals to the immobilized
ligand at an analytical level, which lowers costs in the high-
throughput screening of new catalysts and reactions.35–39
Off-Column Diels-Alder-Reaction
MATERIALS AND METHODS
A mixture of (E)-1-Methoxy-3-trimethylsilyloxy-1,3-butadiene (Danishefsky’s
diene, 52.2 mg, 0.34 mmol), freshly distilled benzaldehyde (28.9 mg,
0.29 mmol), and tetradecene (7.68 μmol) in pentane (1.5 mL) was added
to the catalyst (5 mol%, Eu(hfc)3: 18.5 mg, Gd(hfc)3: 18.6 mg). The flask
was sealed and stirred under the given conditions. For the GC analysis,
0.10 mL was taken from the flask, filtered, and mixed with TFA (50% in
DCM, 25.0 μL) and diluted with pentane. For quantitative analysis the
free induction decay (FID) signal was used and to calculate conversions
the integral was corrected by the number of carbon atoms.
General
All solvents and reagents were obtained from ABCR, Acros, Sigma-
Aldrich, or VWR and were used without further purification unless
otherwise noted. Nuclear magnetic resonance (1H NMR and 13C
NMR) spectra were recorded at 500 and 125 MHz, respectively, on a
Bruker Avance 500 spectrometer (Rheinstetten, Germany) at room
temperature. Chemical shifts (in ppm) were referenced to residual
solvent protons.40 GC-MS measurements were performed on a Trace GC
Ultra single quadrupole ISQ mass spectrometer (Thermo Scientific, San
Jose, CA) equipped with a split injector (250°C), an on-column cold injector
(2min secondary N2-cooling time), and a flame ionization detector (250°C).
Electron impact mass spectra were recorded at 70 eV. IR spectra were
recorded on a Nicolet 6700 FT-IR with smart iTR ATR device (Thermo
Scientific). [(1R,4S)-3-Heptafluorobutanoyl-10-propylenoxycamphor]-
polysiloxane in selector concentrations of 20% were prepared as
reported previously.17 Fused silica capillaries (0.25 mm I.D.), obtained
from Microquartz (Munich, Germany), were coated by the static
method described by Grob.41 For cryo-focusing a cryogenic CO2 cold
trap system by SGE Analytical Science (Victoria, Australia) was
installed according to the experimental setup outlined in Figure 2.
On-Column Diels-Alder-Reaction (ocRGC)
For the on-column measurements freshly distilled benzaldehyde
(1 eq), (E)-1-Methoxy-3-trimethylsilyloxy-1,3-butadiene (Danishefsky’s
diene, 0.9 eq) and tetradecene were mixed in 1 mL pentane. At regular in-
tervals the sample was checked with a reference column (Chirasil-β-Dex,
17 m, 250 nm, 250 μm I.D.) to exclude changes or decomposition of the
sample. The reaction mixture was injected with an on-column syringe
from SGE following the general on-column cold injection techniques with
a secondary N2-cooling time of 2 min. The cryogenic CO2 cooling was
activated and deactivated according the measurement process outlined in
Figure 2 or mentioned in the text. For quantitative analysis the FID signal
was used and to calculate conversions the integral was corrected by the
number of carbon atoms. For the unambiguous assignment of the formed
hetero-Diels-Alder product, pyron 5 was dissolved in n-pentane and
injected via split injection onto the metal(hfc) column (25 m, 250nm,
250 μm I.D.) without cryogenic cooling or additional separation column.
Synthesis of Gadolinium(III)-tris[(1R,4S)-3-
heptafluorobutanoyl-camphor] (Gd(hfc)3) 1
Gadolinium(II)-acetate hydrate (337 mg, 1,00 mmol) was added to a so-
lution of [(1R,4S)-3-Heptafluorobutanoyl-camphor] (200 mg, 574 μmol)
and sodium carbonate (120 mg, 1.13 mmol) in dichloromethane
(25.0 mL) and refluxed for 3 h. The reaction mixture was diluted with wa-
ter and extracted with pentane. The organic extracts were washed with
water, dried over MgSO4, and the solvent was removed under vacuum
to yield gadolinium(III)-tris[(1R,4S)-3-heptafluorobutanoyl-camphor] (1,
405 mg, 338 μmol, 58%) as a yellow solid. ATR-FTIR: υ = 2965, 1647,
1522, 1342, 1200, 1212, 1115, 896, 748 cm-1. HR-MS (FAB+, m/z): calc.
GdC42H42F21O6 [M]: 1199.1887, found: 1199.1866.
RESULTS AND DISCUSSION
To extend the scope of ocRGC of higher-order reactions
to asymmetric catalysis, we shifted our attention to the
Danishefsky-hetero-Diels-Alder-reaction. In a prescreening
we found some interesting activity of gadolinium(III)-tris
[(1R,4S)-3-heptafluorobutanoyl-camphor] (Gd(hfc)3) complexes
as chiral Lewis acid catalyst (Scheme 1).
To perform more systematic studies we developed a strategy
to immobilize Gd(hfc)3 1 to polysiloxane via a propyleneoxy linker
attached to C10 in the camphor moiety, resulting in gadolinium
(III)-tris[(1R,4S)-3-heptafluorobutanoyl-10-propyleneoxycamphor]-
polysiloxane (Gd(hfpc)3@PS) 2. This polymeric catalyst al-
lows fabricating reactor capillaries for ocRGC that enables
a fast and efficient screening of reactions of higher-order
like the Diels-Alder-reaction where a diene and dienophile
reacts to form six-membered rings. For this purpose Gd
(hfc)3@PS 2 (Fig. 1), a polysiloxan bonded version of Gd
(hfc)3 1, was synthesized with 20% selector content and
coated onto the inner surface of fused-silica capillaries
(0.25 mm I.D.) according to the static method described by
Grob, resulting in a defined polymer film thickness of
Synthesis of Gadolinium(III)-tris[(1R,4S)-3-
heptafluorobutanoyl-10-propylenoxycamphor]-
polysiloxane (Gd(hfpc)3@PS) 2
Gadolinium(III)-tris[(1R,4S)-3-heptafluorobutanoyl-10-propylenoxycam-
phor]-polysiloxane (2) was synthesized according to a procedure
previously published.17 Therefore, [(1R,4S)-3-heptafluorobutanoyl-10-
propylenoxycamphor]-polysiloxane (50.0mg) and gadolinium(III)-acetate
hydrate (18.9mg, 56.5μmol) were reacted and purified to yield 49.1 mg
gadolinium(III)-tris[(1R,4S)-3-heptafluorobutanoyl-10-propylenoxycamphor]-
polysiloxane as a red oil. ATR-FTIR: υ = 2962, 1653, 1648, 1559, 1540, 1521,
1507, 1457, 1258, 1231, 1008, 793, 700 cm-1.
Synthesis of 2-Phenyl-2,3-dihydro-4H-pyran-4-one 5
2-Phenyl-2,3-dihydro-4H-pyran-4-one was synthesized based on the
method published by Schurig and colleagues.4 (E)-1-Methoxy-3-
trimethylsilyloxy-1,3-butadiene (Danishefsky’s diene, 107 mg, 0.62 mmol)
and freshly distilled benzaldehyde (62.6 mg, 0.59 mmol) were added to
a solution of europium(III)-tris[(1R,4S)-3-heptafluorobutanoyl-camphor]
(37.0 mg, 5 mol%) in n-hexane (3.00 mL). The reaction mixture was
stirred at room temperature till completion (monitored by thin-layer
chromatography [TLC] and GC) and was quenched by adding of
trifluoroacetic acid (0.5% in trifluoroacetic acid [TFA], 5.00 mL). The desired
product was purified by column chromatography (silica gel, n-hexane/
diethyl ether 3:2) and isolated as a yellow oil (101 mg, 0.58 mmol, 98%).
1H-NMR (500.13MHz, CDCl3): δ = 7.49-7.40 (m, 6H, H-aryl, - = CHO-), 5.53
(d, 1H, J = 6.00Hz, -COCH = -), 5.43 (dd, 1H, J = 14.53Hz, J = 2.73 Hz, -CH-
Ar), 2.92 (dd, 1H, J = 15.73Hz, J = 15.73 Hz, -COCH2-), 2.66 (dd, 1H,
Scheme 1. Danishefsky-hetero-Diels-Alder-reaction of (E)-1-methoxy-3-
trimethylsilyloxy-1,3-butadiene (Danishefsky’s diene, 3) with benzaldehyde 4
forming the chiral pyron 5 after simultaneous elimination of trimethylsilanol
and methanol by traces of water at these low substrate concentrations.
Chirality DOI 10.1002/chir