Asymmetric Organocatalytic Cyclopropanation
bromo-3-keto ester (0.3 mmol, 1.2 equiv.), catalyst (0.05 mmol,
20mol-%), and triethylamine (0.3 mmol, 1.2 equiv.) were added se-
quentially in toluene (1 mL). The reaction was stirred at 4 °C over-
night. Then, the crude product was purified by column chromatog-
raphy to furnish cyclopropane adducts 3.
determined by HPLC with a Chiralpak® IC column: (n-hexane/
iPrOH = 80:20, λ = 220 nm), 1 mL/min; tR = major enantiomer
12.3 min, minor enantiomer 17.6 min.
(1S,2R,3S)-Methyl 1-Acetyl-2-formyl-3-(4-bromophenyl)cycloprop-
anecarboxylate (3f): 75 mg (92% yield). Colorless oil. 1H NMR
(400 MHz, CDCl3 TMSint): δ = 9.73 (d, J = 4.3 Hz, 1 H), 7.63 (d,
J = 8.5 Hz, 2 H), 7.24 (d, J = 8.5 Hz, 2 H), 4.05 (s, 3 H), 4.01 (d,
J = 7.7 Hz, 1 H), 3.92 (d, J = 7.7, JЈ = 4.3 Hz, 1 H), 2.21 (s, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 195.5, 195.4, 167.6, 139.2,
129.6, 129.5, 122.5, 53.8, 52.0, 37.6, 36.7, 29.3 ppm. [α]D = –51.4
(c = 1.0, CHCl3). HRMS (ESI): calcd. for C14H12BrO3 [M + H –
H2O]+ 306.9964; found 306.9963. The enantiomeric excess was de-
termined by HPLC with a Chiralpak® IC column: (n-hexane/
iPrOH = 90:10, λ = 220 nm), 1 mL/min; tR = major enantiomer
11.0 min, minor enantiomer 11.5 min.
(1S,2R,3S)-Ethyl 1-Acetyl-2-formyl-3-phenylcyclopropanecarboxyl-
ate (3a): 58 mg (90% yield). Colorless oil. 1H NMR (400 MHz,
CDCl3, TMSint): δ = 9.50 (d, J = 4.8 Hz, 1 H), 7.35–715 (m, 5 H),
4.38–4.26 (m, 2 H), 3.89 (d, J = 7.6 Hz, 1 H), 3.49 (dd, J = 4.8,
7.6 Hz, 1 H), 1.98 (s, 3 H), 1.33 (t, J = 7.2 Hz, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 196.4, 196.0, 167.1, 131.3, 128.6,
128.2, 128.2, 62.6, 51.6, 37.2, 36.8, 29.2, 14.0 ppm. HRMS: calcd.
for C15H16NaO4 [M + Na]+ 283.0941; found 283.0950. [α]D = –66.8
(c = 1.0, CHCl3). The enantiomeric excess was determined by
HPLC with a Chiralcel® ODH column: (n-hexane/iPrOH = 90:10,
λ = 240 nm), 1 mL/min; tR = major enantiomer 10.8 min, minor
enantiomer 17.3 min.
(1S,2R,3R)-Ethyl 1-Acetyl-2-butyl-3-formylcyclopropanecarboxyl-
ate (3g): 57 mg (95% yield). Colorless oil. 1H NMR (300 MHz.
CDCl3, TMSint): δ = 9.28 (d, J = 5.0 Hz, 1 H), 4.34–4.20 (m, 2
H), 2.82–2.76 (m, 1 H), 2.61–2.52 (m, 1 H), 1.36–1.26 (m,10 H),
0.92–0.84 (m, 5 H) ppm. 13C NMR (100 MHz. CDCl3): δ = 198.8,
196.9, 167.7, 62.3, 52.3, 49.5, 40.0, 34.2, 31.1, 25.4, 22.1, 14.0, 13.9
ppm. HRMS: calcd. for [C13H20NaO4]+ 263.1254; found 263.1255.
The enantiomeric excess was determined by Chiral GC analysis:
alpha-DEX, 120, 30 m, 0.25 mm, Supelco, initial temperature
50 °C, 10 °C/min rate 50–200 °C, hold time 1 min, 2 °C/min rate
(1S,2R,3S)-Methyl 1-Acetyl-2-formyl-3-phenylcyclopropanecarbox-
1
ylate (3b): 55 mg (90% yield). Colorless oil. H NMR (400 MHz,
CDCl3, TMSint): δ = 9.57 (d, J = 4.5 Hz, 1 H), 7.35–7.20 (m, 5
H), 3.93 (d, J = 7.6 Hz, 1 H), 3.91 (s, 3 H), 3.49 (dd, J = 7.6, JЈ =
4.5 Hz, 1 H), 2.02 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 196.4, 196.0, 168.9, 131.6, 128.9, 128.5, 128.4, 64.0, 53.5, 51.7,
37.5, 37.2, 29.4 ppm. HRMS: calcd. for C14H14NaO4 [M +
Na]+ 283.0891; found 283.0791. [α]D = –56.2 (c = 1.0, CHCl3). The
enantiomeric excess was determined by HPLC with a Chiralpak®
200–240 °C, hold time 10 min. Linear velocity 25.4 cm/s. tR
=
IC column: (n-hexane/iPrOH = 95:5, λ = 254 nm), 1 mL/min; tR
=
major enantiomer 26.7 min, minor enantiomer 29.2 min.
major enantiomer 26.2 min, minor enantiomer 28.0 min.
(1S,2R,3R)-Ethyl 1-Acetyl-2-ethyl-3-formylcyclopropanecarboxylate
(3h): 48 mg (91% yield). Colorless oil. 1H NMR (300 MHz.
CDCl3, TMSint): δ = 9.41 (d, J = 4.8 Hz, 1 H), 4.45–4.30 (m, 2
H), 2.91 (dd, J = 7.1, JЈ = 5.0 Hz, 1 H), 2.70–2.65 (m, 1 H), 2.46
(s, 3 H), 1.60–1.40 (m, 5 H), 1.10 (t, J = 7.2 Hz, 3 H) ppm. 13C
NMR (100 MHz. CDCl3): δ = 198.7, 197.6, 168.4, 63.0, 50.3, 40.6,
36.5, 30.2, 20.0, 14.7, 14.0 ppm. HRMS: calcd. for [C9H11NaO4]+
235.0941; found 235.0943. The enantiomeric excess was determined
by Chiral GC analysis: alpha-DEX, 120, 30 m, 0.25 mm, Supelco,
initial temperature 50 °C, 10 °C/min rate 50–200 °C, hold time
1 min, 2 °C/min rate 200–240 °C, hold time 10 min. Linear velocity
25.4 cm/s. tR = major enantiomer 22.3 min, minor enantiomer
22.1 min.
(1S,2R,3S)-Ethyl 1-Acetyl-2-formyl-3-(4-nitrophenyl)cyclopropane-
carboxylate (3c): 67 mg (88% yield). Colorless oil. 1H NMR
(400 MHz, CDCl3 TMSint): δ = 9.58 (d, J = 3.8 Hz, 1 H), 8.17 (d,
J = 8.9 Hz, 2 H), 7.36 (d, J = 8.9 Hz, 2 H), 4.40–4.30 (m, 2 H),
3.92 (d, J = 7.6 Hz, 1 H), 3.92 (d, J = 7.6, JЈ = 3.8 Hz, 1 H), 2.05
(s, 3 H), 1.35 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3 TMSint): δ = 199.1, 195.4, 166.7, 147.8, 139.4, 129.7, 124.0,
63.2, 52.2, 37.6, 36.5, 29.5, 14.29 ppm. [α]D = –75.4 (c = 1.0,
CHCl3). HRMS (ESI): calcd. for C15H15NNaO6 [M + Na]+
328.0792; found 328.0788. The enantiomeric excess was determined
by HPLC with a Chiralcel® ODH column: (n-hexane/iPrOH =
90:10, λ = 240 nm), 1 mL/min; tR = major enantiomer 10.8 min,
minor enantiomer 17.3 min.
(1S,2R,3S)-tert-Butyl 1-Acetyl-2-formyl-3-phenylcyclopropanecarbo-
xylate (3i): 49 mg (68% yield). Colorless oil. H NMR (400 MHz,
(1S,2R,3S)-Methyl
1-Acetyl-2-formyl-3-(4-nitrophenyl)cycloprop-
1
anecarboxylate (3d): 64 mg (88% yield). Colorless oil. 1H NMR
(400 MHz, CDCl3 TMSint): δ = 9.60 (d, J = 3.6 Hz, 1 H), 8.17 (d,
J = 8.8 Hz, 2 H), 7.36 (d, J = 8.9 Hz, 2 H),3.89 (s, 3 H), 3.87 (d, J
= 7.6 Hz, 1 H), 3.60 (d, J = 7.6, JЈ = 3.6 Hz, 1 H), 2.06 (s, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 207.3, 195.4, 166.5, 148.8,
139.2, 129.7, 124.0, 53.8, 52.0, 37.6, 36.7, 29.5 ppm. [α]D = –59.2
(c = 1.0, CHCl3). HRMS (ESI): calcd. for C14H14NO6 [M + H]+
292.0816; found 292.0806. The enantiomeric excess was determined
by HPLC with a Chiralpak® IC column: (n-hexane/iPrOH = 95:5,
λ = 254 nm), 1 mL/min; tR = major enantiomer 62.9 min, minor
enantiomer 70.8 min.
CDCl3 TMSint): δ = 9.70 (d, J = 4.8 Hz, 1 H), 7.35–7.25 (m, 5 H),
4.06 (d, J = 7.6 Hz, 1 H), 3.66 (d, J = 7.6, JЈ = 4.8 Hz, 1 H), 2.22
(s, 3 H), 1.75 (s, 9 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
202.4, 196.6, 166.1, 131.9, 128.8, 128.5, 128.2, 84.2, 53.0, 49.9, 37.4,
36.6, 28.1 ppm. [α]D = –5.2 (c = 1.0, CHCl3). HRMS (ESI): calcd.
for C17H20NaO4 [M + Na]+ 311.1254; found 311.1253. The enan-
tiomeric excess was determined by HPLC with a Chiralpak® IC
column: (n-hexane/iPrOH = 90:10, λ = 254 nm), 1 mL/min; tR
=
major enantiomer 31.5 min, minor enantiomer 38.5 min.
(1S,2R,3S)-Ethyl 2-Formyl-3-phenyl-1-pivaloylcyclopropanecarbox-
ylate (3j): 57 mg (76% yield). Colorless oil. 1H NMR (400 MHz,
CDCl3 TMSint): δ = 9.41 (d, J = 5.1 Hz, 1 H), 7.40–7.25 (m, 5 H),
(1S,2R,3S)-Methyl 1-Acetyl-2-formyl-3-(4-cyanophenyl)cycloprop-
anecarboxylate (3e): 63 mg (93% yield). Colorless oil. 1H NMR
(400 MHz, CDCl3 TMSint): δ = 9.57 (d, J = 3.6 Hz, 1 H), 7.60 (d, 4.40–4.30 (m, 2 H), 3.97 (d, J = 7.5 Hz, 1 H), 3.54 (d, J = 7.5, JЈ
J = 8.4 Hz, 2 H), 7.29 (d, J = 8.4 Hz, 2 H), 3.88 (s, 3 H), 3.87 (d,
= 5.1 Hz, 1 H), 1.25 (t, J = 7.2 Hz, 3 H), 0.92 (s, 9 H) ppm. 13C
J = 7.6 Hz, 1 H), 3.55 (d, J = 8.0, JЈ = 3.6 Hz, 1 H), 2.04 (s, 3 H) NMR (100 MHz, CDCl3): δ = 204.6, 196.6, 167.0, 128.8, 128.4,
ppm. 13C NMR (100 MHz, CDCl3): δ = 208.4, 195.5, 167.3, 137.2,
132.5.8, 129.5, 118.4, 112.3, 53.8, 51.9, 37.4, 36.9, 29.5 ppm. [α]D
= –62.2 (c = 1.0, CHCl3). HRMS (ESI): calcd. for C15H13NO4
[M + H]+ 272.0917; found 272.0906. The enantiomeric excess was
128.4, 62.8, 52.2, 36.9, 35.6, 29.5, 14.2 ppm. [α]D = –51.1 (c = 1.0,
CHCl3). HRMS (ESI): calcd. for C18H22NaO4 [M
+
Na]+
325.1410; found 325.1415. The enantiomeric excess was determined
by HPLC with a Chiralpak® IC column: (n-hexane/iPrOH = 90:10,
Eur. J. Org. Chem. 2009, 3075–3080
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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