Full Paper
KH2PO4 (136 g), solid NaOH (23.3 g) and both were dissolved in
H2O (1000 cm3). Extracts were dried over technical grade Na2SO4 or
MgSO4. Analytical thin layer chromatography (TLC) was performed
on pre-coated Merck silica gel 60 F254 plates (0.25 mm). Visualisa-
tion was achieved using ultraviolet light (l=254 nm) or by dipping
in cerium ammonium molybdate (CAM) stain [(NH4)6Mo7O24·4H2O
(50 g), Ce(SO4)2 (10 g) and H2SO4 (100 cm3) in water (900 cm3)] or
potassium permanganate stain [KMnO4 (10 g), K2CO3 (65 g) and
aqueous NaOH solution (1N, 15 cm3) in water (1000 cm3)] followed
by heating. Flash column chromatography was carried out on
Fluka silica gel 60 (230–400 mesh). Concentration in vacuo was
performed at ~20 mbar and 408C, drying at ~10ꢀ2 mbar and rt
unless otherwise stated (caution: some intermediates and products
a mixture of n-pentane:EtOAc 4:1 was used). The resulting solution
was concentrated in vacuo and the crude product was then puri-
fied by flash-column chromatography on silica gel (n-pentane:E-
tOAc).
5.0 mmol scale: To a solution of the freshly purified (flash column
chromatography, n-pentane:EtOAc) aldehyde (5.0 mmol) in n-hep-
tane (40 cm3) at ambient temperature were added (S)-2-(fluorodi-
phenylmethyl)-pyrrolidine (S)-1 (1.0 mmol) in n-heptane (10 cm3),
tert-butyl p-tolyloxycarbamate (6.0 mmol) and sodium acetate
(7.5 mmol), consecutively. The resulting suspension was then
stirred at ambient temperature for the specified time. The progress
of the reaction was monitored by TLC analysis. Upon consumption
of the starting material, the, thick white suspension was filtered
through a short plug of silica gel and eluted with a mixture of n-
pentane:EtOAc 7:1 (~250 cm3). The resulting solution was concen-
trated in vacuo and the crude product was then purified by flash-
column chromatography on silica gel (n-pentane:EtOAc).
1
are volatile). H NMR, 19F NMR and 13C NMR spectra were recorded
by the NMR service at the Institute of Organic Chemistry (WWU
Mꢃnster) on a Bruker AV 300 MHz, a Bruker AV 400 MHz, Agilent
VVMRS 500 MHz or an Agilent DD2 600 MHz spectrometer at ambi-
ent temperature. Chemical shifts d are reported in ppm relative to
the residual solvent. Coupling constants J are reported in Hz. The
multiplicities are reported as: s=singlet, bs=broad singlet, d=
doublet, t=triplet, q=quartet, qu=quintet, m=multiplet. Melting
points were measured on a Bꢃchi B540 melting point apparatus
and are uncorrected. IR spectra were measured on a PerkinElmer
Spectrum 100 FTIR spectrometer and reported in cmꢀ1. The intensi-
ties of the bands are reported as: w=weak, m=medium, s=
strong. Optical rotations were obtained using a JASCO P-2000 po-
larimeter. HPLC spectra were recorded on an Agilent 1100 series
(DAD, Agilent technologies 1200 series) using Reprosil Chiral-AM
(5 mm, 250ꢂ4.6 mm) and n-hexane/i-propanol as the eluent. GC
spectra were recorded on an Agilent 7890A system using a Supelco
b-DEX 120 column. High-resolution mass spectra (HR ESI MS) were
performed by the MS service at the Institute of Organic Chemistry
(WWU Mꢃnster) on a Bruker Daltonics MicroTof.
General procedure for organocatalytic, enantioselective aziridi-
nation of substrates 19 and 20 (Method B): To a solution of fresh-
ly purified aldehyde (250 mmol) in n-heptane (0.5 cm3) at ambient
temperature were added (S)-2-(fluorodiphenylmethyl)-pyrrolidine
(S)-1 (20 mmol) in n-heptane (0.5 cm3), tert-butyl p-tolyloxycarba-
mate (100 mmol) and sodium acetate (150 mmol), consecutively.
The resulting white suspension was then stirred at ambient tem-
perature for the specified time. The progress of the reaction was
1
monitored by H NMR analysis. Upon consumption of the starting
material, the thick, white suspension was filtered through a short
plug of silica gel and eluted with a mixture of n-pentane:EtOAc 7:1
(~20 cm3). The solution was concentrated in vacuo and the result-
ing crude product was then purified by flash-column chromatogra-
phy on silica gel (n-pentane : EtOAc).
Full experimental procedures are provided in the Supporting Infor-
mation.
General procedure for the enantioselective, organocatalytic
aziridination of a,b-unsaturated enals
Acknowledgements
General procedure for the optimisation reactions (Tables 1–3):
To a solution of 2-benzylacrylaldehyde (100 mmol) in the specified
solvent (0.5 cm3) at ambient temperature were added (S)-2-(fluoro-
diphenylmethyl)-pyrrolidine (S)-1 (20 mmol) in the specified solvent
(0.5 cm3), tert-butyl p-tolyloxycarbamate (120 mmol) and the speci-
fied base (150 mmol). The resulting suspension was then stirred at
the specified temperature for the specified time. The progress of
the reaction was monitored by TLC. Upon consumption of the
starting material, the thick, white suspension was directly loaded
on a silica gel column and eluted with a mixture of n-pentane:E-
tOAc/10:1 to obtain the crude product (In cases in which the con-
centrations were c=0.05 mol·Lꢀ1 and 0.01 mol·Lꢀ1, the reaction
mixtures were first filtered and then concentrated in vacuo).
We gratefully acknowledge generous financial support from
the WWU Mꢃnster Graduate School of Chemistry (IGM), and
the Deutsche Forschungsgemeinschaft, DFG EXC 1003 “Cells in
Motion - Cluster of Excellence, Mꢃnster”, Germany.
Keywords: aziridination
·
catalysis
·
enantioselectivity
·
fluorine · gauche effect · pre-organisation
[1] a) R. Hili, A. K. Yudin, Chem. Eur. J. 2007, 13, 6538–6542; b) N. Assem, R.
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General procedure for the organocatalytic, enantioselective azir-
idination of substrates 15, 16, 17, 18 and 21 (Method A):
0.1 mmol scale: To a solution of the freshly purified (flash column
chromatography, n-pentane:EtOAc) aldehyde (100 mmol) in n-hep-
tane (0.5 cm3) at ambient temperature were added (S)-2-(fluorodi-
phenylmethyl)-pyrrolidine (S)-1 (20 mmol) in n-heptane (0.5 cm3),
tert-butyl p-tolyloxycarbamate (120 mmol) and sodium acetate
(150 mmol). The resulting suspension was then stirred at ambient
temperature for the specified time. The progress of the reaction
was monitored by TLC analysis. Upon consumption of the starting
material, the thick, white suspension was filtered through a short
plug of silica gel and eluted with a mixture of n-pentane:EtOAc 7:1
(approximately 20 cm3, in the case of the five-membered ring
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gull, G. Dickmeiss, K. L. Jensen, P. T. Franke, N. Holub, K. A. Jørgensen,
7904–7917; g) A. Desmarchelier, D. P de Sant’Ana, V. Terrasson, J. M.
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