Aziridination of Cyclic Enones
8:2) in 84% yield and 98% ee. HPLC analysis on a Chiralcel AD-H
column: 90:10 hexane/iPrOH, flow rate 0.75 mLminÀ1, l=214, 254 nm:
tminor =5.98 min, tmajor =6.86 min. [a]RDT =À106.7 (c=0.98, CHCl3, 98%
ee); 1H NMR: d=1.03 (s, 3H), 1.21 (s, 3H), 1.26–1.38 (m, 1H), 1.44 (s,
9H), 1.88–1.95 (m, 1H), 2.12–2.20 (m, 1H), 2.35 (ddd, J=19.23, 8.93,
19.11 Hz, 1H), 2.64–2.67 (dd, J=5.89, 1.47 Hz, 1H), 2.92 ppm (d, J=
5.91 Hz, 1H); 13C NMR: d=23.4 (CH3), 27.8 (CH3), 28.0 (CH3), 30.42
(CH2), 33.82 (CH2), 44.25 (CH), 50.2 (CH), 82.3 (C), 160.5 (C),
204.8 ppm (C); ESIMS: m/z: 262 [M+Na]+, 240 [M+1]+.
Experimental Section
General Methods
The H and 13C NMR spectra were recorded at 600 and 150 MHz, respec-
1
1
tively. The chemical shifts (d) for H and 13C are given in ppm relative to
residual signals of the solvents (CHCl3). Coupling constants are given in
Hz. Carbon types were determined from distortionless enhancement by
polarization transfer (DEPT) 13C NMR spectroscopy experiments. The
following abbreviations are used to indicate the multiplicity: s, singlet; d,
doublet; t, triplet; q, quartet; m, multiplet; brs, broad signal. Purification
of the reaction products was carried out by flash chromatography (FC)
on silica gel (230–400 mesh). For thin-layer chromatography (TLC) anal-
ysis throughout this work, Merck precoated TLC plates (silica gel 60
GF254, 0.25 mm) were used. Optical rotations are reported as follows:
[a]RDT (c in g per 100 mL, solvent). The diastereomeric ratio (d.r.) was de-
termined by 1H NMR spectroscopic analysis of the crude reaction mix-
ture, and confirmed by HPLC analysis on chiral stationary phases col-
umns. High-performance liquid chromatography (HPLC) was performed
3 f: Prepared by following the general procedure using catalyst salt A to
furnish the crude product as a single diastereomer. The title compound
was isolated as a colorless oil by column chromatography (hexane/ethyl
acetate 8:2) in 33% yield and 98% ee. The ee was determined by HPLC
analysis on a Chiralcel AD-H column: 99:1 hexane/iPrOH, flow rate
0.650 mLminÀ1
, l=214, 254 nm: tminor =18.44 min, tmajor =20.47 min.
[a]RDT =+43.4 (c=0.65, CHCl3, 98% ee); 1H NMR: d=0.88 (s, 3H), 1.00
(s, 3H), 1.44 (s, 9H), 1.78–1.83 (m, 2H), 1.94 (d, J=14.60 Hz, 1H), 2.58
(d, J=14.00 Hz, 1H), 2.87 (d, J=6.46 Hz, 1H), 2.97 ppm (t, J=6.18 Hz,
1H); 13C NMR: d=27.4 (CH3), 27.8 (CH3), 30.8 (CH3), 36.8 (CH2), 37.7
(C), 41.0 (CH), 42.8 (CH), 48.8 (CH2), 82.3 (C), 160.3 (C), 206.0 ppm
(C); ESIMS: m/z: 262 [M+Na]+, 240 [M+1]+.
an Agilent 1100 series instrumentation.
A Daicel Chiralpak AD-H
column with iPrOH/hexane as the eluent proved to be effective for all
the aziridines synthesized. HPLC traces were compared with racemic
samples obtained by carefully mixing the two product antipodes obtained
by performing the individual reactions with 9-aminoACHTNUTRGNEUNG(9-deoxy)epi-hydro-
quinine (catalyst salt A) and its pseudoenantiomer 9-amino
hydroquinidine (catalyst salt B) separately.
3g: Prepared by following the general procedure over the course of 48 h
using catalyst salt A to furnish the crude product as a single diastereo-
mer. The title compound was isolated as a colorless oil by column chro-
matography (hexane/Et2O 7:3) in 93% yield and 95% ee. The ee was de-
termined by HPLC analysis on a Chiralcel AD-H column: 95:5 hexane/
ACHTUNGTREN(NUNG 9-deoxy)epi-
Syntheses
iPrOH, flow rate 0.75 mLminÀ1
, l=214, 254 nm: tminor =12.52 min,
tmajor =15.15 min. [a]RDT =À59.7 (c=0.73, CHCl3, 95% ee); 1H NMR: d=
1.48 (s, 9H), 1.51–1.59 (m, 2H), 1.86–1.98 (m, 2H), 2.01–2.07 (m, 1H),
2.35–2.41 (m, 1H), 2.46 (d, J=14.45 Hz, 1H), 3.05 (s, 1H), 3.23 (d, J=
14.53 Hz, 1H), 7.20 (d, J=7.79 Hz, 2H), 7.23–7.27 (m, 1H), 7.28–
7.32 ppm (m, 2H); 13C NMR: d=1.2 (CH3), 17.6 (CH2), 26.3 (CH2), 28.2
(CH), 36.3 (CH2), 41.5 (CH2), 48.9 (CH), 51.3 (C), 82.4 (C), 127.4 (CH),
128.9 (CH), 129.6 (CH), 136.5 (C), 205.2 ppm (C); ESIMS: m/z: 324
[M+Na]+.
General procedure for the organocatalytic asymmetric aziridination of
cyclic enones (Table 2): All the reactions were carried out with no pre-
cautions to exclude air or moisture and using the appropriate catalytic
salt combination A or B. In an ordinary vial equipped with a Teflon-
coated stirrer bar, the chiral primary amine (0.04 mmol, 13 mg,
20 mol%) was dissolved in CHCl3 (0.8 mL). After addition of N-Boc
phenylglycine (0.06 mmol, 15 mg, 30 mol%), the solution was stirred for
10 min at room temperature. Cyclic enone 1 (0.24 mmol, 1.2 equiv) was
added, and stirring continued for an additional 10 min. Then nucleophile
2 (0.2 mmol) was added followed by the addition of NaHCO3 (0.4 mmol,
32 mg, 2 equiv) in one portion. Stirring was continued for 1 d, then the
crude reaction mixture was diluted with CH2Cl2 (1 mL) and flushed
through a short plug of silica, using CH2Cl2/Et2O 1:1 as the eluent. The
solvent was removed in vacuo, and the residue was purified by flash chro-
matography (FC) to yield the desired aziridine 3.
3h: Prepared by following the general procedure using catalyst salt A to
furnish the crude product as a single diastereomer. The title compound
was isolated as a colorless oil by column chromatography (hexane/Et2O
7:3) in 90% yield and 98% ee. The ee was determined by HPLC analysis
on
a
Chiralcel AD-H column: 95:5 hexane/iPrOH, flow rate
0.75 mLminÀ1, l=214, 254 nm: tmajor =8.07 min, tminor =8.88 min. [a]RDT
=
À103.2 (c=0.8, CHCl3, 98% ee); 1H NMR: d=0.92–1.01 (m, 1H), 1.44
(s, 9H), 1.60–1.67 (m, 1H), 1.67–1.68 (m, 2H), 1.79–1.85 (m, 1H), 2.23–
2.30 (m, 1H), 2.39–2.46 (m, 1H), 2.72–2.78 (m, 1H), 2.84–2.88 (m, 1H),
3.00–3.02 ppm (dd, J=1.61, 7.22 Hz, 1H); 13C NMR: d=23.67 (CH2),
23.85 (CH2), 28 (CH2), 28.08 (CH3), 40.57 (CH2), 40.99 (CH), 47.57
(CH), 82.20 (C), 161.11 (C), 209.50 ppm (C); ESIMS: m/z: 248
3b: Prepared by following the general procedure using catalyst salt A to
furnish the crude product as a single diastereomer. The title compound
was isolated as a colorless oil by column chromatography (hexane/ace-
tone 8:2) in 73% yield and 99% ee. The ee was determined by HPLC
analysis on a Chiralcel AD-H column: 90:10 hexane/iPrOH, flow rate
AHCTUNGTRENNUNG
[M+Na]+, 226 [M+1]+.
0.75 mLminÀ1, l=214, 254 nm: tmajor =7.6 min, tminor =8.2 min. [a]RDT
=
À95.5 (c=0.74, CHCl3, 99% ee); 1H NMR: d=1.45 (s, 9H), 1.63–1.68
(m, 1H) 1.74–1.82 (m, 1H), 1.92–1.08 (m, 2H), 2.20–2.27 (m, 1H), 2.47–
2.52 (m, 1H), 2.88 (d, J=5.89 Hz, 1H), 3.05–3.09 ppm (m, 1H);
13C NMR: d=17.5 (CH2), 22.8 (CH2), 28.0 (CH3), 37.1 (CH2), 40.6 (CH),
43.4 (CH), 82.5 (C), 160.8 (C), 204.5 ppm (C); ESIMS: m/z: 234
[M+Na]+, 212 [M+1]+.
3i: Prepared by following the general procedure using catalyst salt A to
furnish the crude product as a single diastereomer. The title compound
was isolated as a pale yellow oil by column chromatography (hexane/
ethyl acetate 8:2) in 39% yield and 93% ee. The ee was determined by
HPLC analysis on a Chiralcel AD-H column: 90:10 hexane/iPrOH, flow
rate 0.750 mLminÀ1, l=214, 254 nm: tminor =10.66 min, tmajor =11.42 min.
1
[a]RDT =+43.4 (c=0.72, CHCl3, 93% ee); H NMR: d=1.46 (s, 9H), 1.93–
3d: Prepared by following the general procedure using catalyst salt A to
furnish the crude product as a single diastereomer. The title compound
was isolated as a white solid by column chromatography (hexane/Et2O/
CHCl3 5:3:2) in 75% yield and 92% ee. The ee was determined by
HPLC analysis on a Chiralcel AD-H column: 95:5 hexane/iPrOH, flow
2.03 (m, 1H), 2.07–2.22 (m, 2H), 2.47–2.51 (m, 1H), 3.01 (d, J=3.09 Hz,
1H), 3.38 ppm (t, J=3.11 Hz, 1H); 13C NMR: d=21.5 (CH2), 28.1 (CH3),
31.7 (CH2), 44.1 (CH), 44.3 (CH), 129.9 ppm (C) ; ESIMS: m/z: 220
[M+Na]+, 198 [M+1]+.
rate 0.75 mLminÀ1
, l=214, 254 nm: tminor =8.20 min tmajor =10.38 min.
3j: Prepared by following the general procedure over the course of 72 h
to furnish the crude product as a single diastereomer. The title compound
was isolated as a colorless oil by column chromatography (hexane/ace-
tone 8:2) in 52% yield and 85% ee. The ee was determined by HPLC
analysis on a Chiralcel AD-H column: 90:10 hexane/iPrOH, flow rate
1H NMR: d=1.44 (s, 3H), 1.51 (s, 9H), 1.64–1.75 (m, 2H), 2.01–2.10 (m,
2H), 2.14–2.22 (m, 1H), 2.44–2.52 (m, 1H), 2.83 ppm (s, 1H); 13C NMR:
d=17.4 (CH), 20.2 (CH3), 27.9 (CH3), 29.1 (CH), 36.0 (CH), 47.4 (C),
49.5 (CH), 81.9 (C), 158.9 (C), 205.4 ppm (C); ESIMS: m/z: 248
[M+Na]+, 226 [M+1]+.
0.750 mLminÀ1
,
l=214, 254 nm: tminor =6.83 min, tmajor =12.54 min.
3e: Prepared by following the general procedure using catalyst salt A to
furnish the crude product as a single diastereomer. The title compound
was isolated as a white solid by column chromatography (hexane/acetone
[a]RDT =+39.9 (c=0.90, CHCl3, 85% ee); 1H NMR: d=1.45 (s, 9H), 1.51
(s, 3H), 1.94–2.04 (m, 2H), 2.19–2.28 (m, 1H), 2.46–2.54 (m, 1H),
2.83 ppm (s, 1H); 13C NMR: d=19.5 (CH3), 26.3 (CH2), 28.1 (CH3), 33.6
Chem. Asian J. 2010, 5, 1652 – 1656
ꢄ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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