Highly Substituted Acylcyclopropanes
FULL PAPER
0.34 mmol, 92%, 92% ee) as colourless oil. RF = 0.63 (PE/Et2O,
128.3 (CH, o-/m-Ph), 132.3 (CH, p-Ph), 138.2 (Cq, i-Ph), 200.0
1
3
3:1). H NMR (300 MHz, CDCl3): δ [ppm] = 1.38 (d, J3Ј,3Ј-CH3
6.6 Hz, 3 H, 3Ј-CH3), 2.14 (ddq, J3Ј,3Ј-CH3 = 6.6 Hz, J1Ј,3Ј = 4.5,
=
(CO). IR (film) ν [cm–1] = 2960, 2930, 2869 ν(Caliph–H), 1665
˜
3
3
ν(C=O). C13H16O (188.12): calcd. C 82.94, H 8.57, found C 82.78,
H 8.72. [α]2D0 = –85.0 (c = 0.59, CHCl3). rac-5m (41 mg, 0.22 mmol,
88%) was obtained from rac-2m (84 mg, 0.25 mmol, 1.0 equiv.) by
3
3
3J2Ј,3Ј = 9.3 Hz, 1 H, H-3Ј), 3.00 (t, J1Ј,2Ј = 4.5, J1Ј,3Ј = 4.5 Hz, 1
3
3
H, H-1Ј), 3.20 (dd, J1Ј,2Ј = 4.5, J2Ј,3Ј = 9.3 Hz, 1 H, H-2Ј), 7.39–
8.17 (m, 12 H, o-,m-,p-Ph, Naphthyl). 13C NMR (75 MHz, CDCl3): method B as colourless liquid.
δ [ppm] = 13.4 (CH3, 3Ј-CH3), 27.5 (CH, C3Ј), 32.4 (CH, C2Ј);
(1S,2S,3R)-1-(2-Isopropyl-3-methylcyclopropyl)-1-phenylmethanone
35.7 (CH, C-1Ј), 125.9, 126.5, 127.5, 127.9, 128.1, 128.2, 128.5,
(5n): Method B: Sodium hydride (60 % in mineral oil, 15 mg,
0.38 mmol 1.2 equiv.) and carbamate 2n (113 mg, 0.32 mmol, 96%
ee, 1.0 equiv.), suspended in DMF (5 mL), were treated according
to method B. Purification by FCC yielded (–)-5n (40 mg,
0.20 mmol, 62%, 96% ee) as colourless liquid. RF = 0.85 (PE/Et2O,
3:1). 1 H NMR (300 MHz, CDCl3 ): δ [ pp m] = 0 . 97 [ d,
3JCH(CH3)2,CH(CH3)2 = 6.0 Hz, 6 H, 2Ј-CH(CH3)2], 1.17 (d,
3J3Ј,3Ј-CH3 = 6.3 Hz, 3 H, 3Ј-CH3), 1.33–1.50 [m, 2 H, 2Ј-CH(CH3)
129.0, 132.7, 133.2, 133.8, 135.0, 138.5 (CH and Cq, C-Ph, C-Naph-
thyl), 199.6 (CO). IR (film) ν [cm–1] = 2919, 2882, 2874 ν(C
–
˜
aliph
H), 1647 ν(C=O). C21H18O (286.37): calcd. C 88.08, H 6.34, found
C 87.76, H 6.13. [α]2D0 = +206.0 (c = 0.77, CHCl3) at 92% ee (er =
96:4). rac-5j (46 mg, 0.16 mmol, 80%) was obtained from carba-
mate rac-2j (82 mg, 0.20 mmol, 1.0 equiv.) by method B as colour-
less oil.
3
3
(1S,2S,3R)-1-[2-(Furan-2-yl)-3-methylcyclopropyl]-1-phenylmeth- 2/2Ј-H], 1.71–1.82 (m, 1 H, 3Ј-H), 2.07 (t, J1Ј,2Ј = 4.2, J1Ј,3Ј
=
anone (5k): Method B: From sodium hydride (60% in mineral oil,
4.2 Hz, 1 H, 1Ј-H), 7.35–7.48 (m, 3 H, p-/m-Ph), 7.86–7.91 (m, 2
13 mg, 0.32 mmol, 92% ee, 1.2 equiv.) and carbamate 2k (101 mg, H, o-Ph). 13C NMR (75 MHz, CDCl3): δ [ppm] = 12.8 (CH3, 3Ј-
0.27 mmol, 1.0 equiv.), suspended in THF (10 mL), (+)-5k (61 mg, CH3), 22.6, 23.3 [CH3, CH(CH3)2], 26.8 [CH, CH(CH3)2], 28.2
0.27 mmol, 98%, 92% ee) was obtained as colourless oil after puri-
(CH, C1Ј), 33.5 (CH, C2Ј), 41.1 (CH, C1Ј), 128.3, 128.8 (CH, o-/
1
fication by FCC. RF = 0.78 (PE/Et2O, 3:1). H NMR (300 MHz, m-Ph), 132.8 (CH, p-Ph), 138.7 (Cq, i-C-Ph), 200.4 (CO). IR (film)
CDCl3): δ [ppm] = 1.11 (d, 3J3Ј,3Ј-CH3 = 6.0 Hz, 3 H, 3Ј-CH3), 1.86–
ν [cm–1] = 2948, 2920, 2865 ν(Caliph–H), 1660 ν(C=O). C14H18O
˜
1.98 (m, 1 H, 3Ј-H), 2.7–2.83 (m, 1 H, 1Ј/2Ј-H), 6.08 (d, J1ЈЈ,2ЈЈ
=
(202.13): calcd. C 83.12, H 8.97, found C 82.95, H 9.17. [α]2D0
=
3
3
3
3.3 Hz, 1 H, Fu-H), 6.24 (dd, J1ЈЈ,2ЈЈ = 3.3, J2ЈЈ,3ЈЈ = 1.8 Hz, 2 H, –19.0 (c = 0.70, CHCl3) at 96 % ee (er = 98:2). rac-5n (75 mg,
4
3
Fu-H), 7.25 (dd, J1ЈЈ,3ЈЈ = 0.6, J2ЈЈ,3ЈЈ = 1.8 Hz, 1 H,Fu-H), 7.36–
7.50 (m, 3 H, m-,p-Ph), 7.92–7.95 (m, 2H o-Ph). 13C NMR
(75 MHz, CDCl3): δ [ppm] = 13.3 (CH3, 3Ј-CH3), 26.6 (CH, C3Ј),
27.9 (CH, C2Ј), 32.6 (CH, C1Ј), 107.6, 110.8 (CH, C-Fu), 128.5,
128.9 (CH, o-,m-Ph), 133.3 (CH, p-Ph), 138.2 (Cq, i-Ph), 141.8,
0.37 mmol, 58%) was obtained from carbamate rac-2n (224 mg,
0.64 mmol, 1.0 equiv.) by method B as colourless liquid.
(1S,2S,3R)-1-(2-Cyclopropyl-3-methylcyclopropyl)-1-phenylmeth-
anone (5o): Method B: From sodium hydride (60% in mineral oil,
33 mg, 0.83 mmol 1.3 equiv.) and carbamate 2o (218 mg,
0.64 mmol, 95% ee, 1.0 equiv.), suspended in THF (5 mL), (–)-5o
(95 mg, 0.47 mmol, 74%, 95% ee) was obtained after purification
by FCC as colourless oil. RF = 0.58 (PE/Et2O, 3:1). 1H NMR
(300 MHz, CDCl3): δ [ppm] = 0.11–0.17 (m, 2 H, H-c-Pr), 0.34–
152.4 (CH and C , C-Fu), 199.8 (CO). IR (film) ν [cm–1] = 2960,
˜
q
2926, 2873 ν(Caliph–H), 1669 ν(C=O). C15H14O2 (226.09): calcd. C
79.62, H 6.24, found C 79.69, H 6.42. [α]2D0 = +177.0 (c = 0.53,
CHCl3) at 92% ee (er = 96:4). rac-5k (134 mg, 0.59 mmol, 80%)
was obtained from carbamate rac-2k (277 mg, 0.75 mmol,
1.0 equiv.) by method B as colourless oil.
3
0.48 (m, 2 H, H-c-Pr), 0.52–0.62 (m, 1 H, H-c-Pr), 1.15 (d, J3Ј,3Ј-
3
3
= 7.5 Hz, 3 H, 3Ј-CH3), 1.24–1.30 (ddd, J1Ј,2Ј = 4.5, J2Ј,3Ј
=
CH3
3
(1r,2t,3t)-1-(2,3-Dimethylcyclopropyl)-1-phenylmethanone (5l):
9.3 Hz, 1 H, 2Ј-H), 1.63–1.73 (m, 1 H, 3Ј-H), 2.07 (t, J1Ј,2Ј = 4.5,
Method B: Sodium hydride (60% in mineral oil, 27 mg, 0.68 mmol
3J1Ј,3Ј = 4.5 Hz, 1 H, 1Ј-H), 7.27–7.40 (m, 3 H, p-/m-Ph), 7.78–7.81
1.2 equiv.) and carbamate 2l (183 mg, 0.57 mmol, 91 % ee, (m, 2 H, o-Ph). 13C NMR (75 MHz, CDCl3): δ [ppm] = 5.3, 5.4,
1.0 equiv.), suspended in THF (5 mL), were treated according to
method B. Purification by FCC yielded 5l (83 mg, 0.48 mmol, 84%)
as colourless oil. RF = 0.44 (PE/Et2O, 3:1). 1H NMR (300 MHz,
8.8 (CH and CH2, c–Pr–C), 13.36 (CH3, 3Ј-CH3), 26.7 (CH, C-3Ј),
33.2 (CH, C-2Ј), 36.5 (CH, C-1Ј), 128.3, 128.8 (CH, o-/m-Ph), 132.8
(CH, p-C-Ph), 138.7 (C , i-C-Ph), 200.4 (CO). IR (film) ν [cm–1] =
˜
q
CDCl3): δ [ppm] = 1.42 (m, 6 H, 2Ј-CH3, 3Ј-CH3), 1.98 (m, 2 H, 2956, 2926, 2865 ν(Caliph–H), 1656 ν(C=O). C14H16O (200.12):
3
2Ј/3Ј-H), 2.26 (t, 3J1Ј,2Ј = 4.5, J1Ј,3Ј = 4.5 Hz,1 H, 1Ј-H), 7.62–7.77 calcd. C 83.96, H 8.05, found C 83.83, H 8.27. [α]2D0 = –50.0 (c =
(m, 3 H, Ph-H), 8.14–8.18 (m, 2 H, Ph-H). 13C NMR (75 MHz,
0.57, CHCl3) at 95% ee (er = 97.5:2.5). rac-5o (28 mg, 0.14 mmol,
CDCl3): δ [ppm] = 12.5 (CH, C2Ј, C3Ј), 26.5 (CH3, 2Ј/3Ј-CH3), 70 %) was obtained from carbamate rac-2o (68 mg, 0.20 mmol,
30.1 (CH, C1Ј), 128.3, 128.8 (CH, o-, m-Ph), 132.8 (CH, p-Ph),
1.0 equiv.) by method B as colourless oil.
138.8 (C , i-Ph), 200.4 (CO). IR (film) ν [cm–1] = 2953, 2928, 2871
˜
q
(1S,2S,3R)-1-(2-Cyclohexyl-3-methylcyclopropyl)-1-phenylmeth-
anone (5p): Method B: Sodium hydride (60% in mineral oil, 17 mg,
0.43 mmol, 1.3 equiv.) and carbamate 2p (145 mg, 0.37 mmol, 95%
ee, 1.0 equiv.), suspended in THF (5 mL), were treated according
to method B. Purification by FCC yielded (–)-5p (70 mg,
0.29 mmol, 78%, 95% ee) as colourless solid. M.p. 111–112°C (PE/
ν(Caliph–H), 1665 ν(C=O). C12H14O (174.10): calcd. C 82.72, H
8.10, found C 82.52, H 8.02.
(1S,2S,3R)-1-(2-Ethyl-3-methylcyclopropyl)-1-phenylmethanone
(5m): Method B: Sodium hydride (60 % in mineral oil, 26 mg,
0.66 mmol 1.2 equiv.) and carbamate 2m (185 mg, 0.55 mmol, 96%
ee, 1.0 equiv.), suspended in THF (5 mL), were treated according to
method B. Purification by FCC yielded (–)-5m (101 mg, 0.53 mmol,
1
Et2O). RF = 0.83 (PE/Et2O, 3:1). H NMR (300 MHz, CDCl3): δ
3
[ppm] = 1.12–1.31, 1.51–1.89 (m, J3Ј,3Ј-CH3 = 6.6 Hz, 16 H, 2Ј/3Ј-
3
3
96 %) as colourless oil. RF = 0.50 (PE/Et2O, 3:1). 1H NMR
H/3Ј-CH3/H-c-Hex), 2.14 (t, J1Ј,2Ј-H = 4.2, J1Ј,3Ј = 4.2 Hz, 1 H,
(300 MHz, CDCl3): δ [ppm] = 1.04 (t, JCH2CH3,CH2CH3 = 5.7 Hz, 1Ј-H), 7.42–7.56 (m, 2 H, H-Ph), 7.96–8.00 (m, 2 H, o-Ph). 13C
3
3 H, CH2CH3), 1.22 (d, 3J3Ј,3Ј-CH3 = 4.8 Hz, 3 H, 3Ј-CH3), 1.53 (m,
2 H, CH2CH3), 1.68–1.75 (m, 1 H, 3Ј-H), 1.78–1.87 (m, 1 H, 2Ј- 32.9, 33.4 (CH and CH2, C2Ј, C3Ј, C-c-Hex), 37.4, 39.7 (CH and
NMR (75 MHz, CDCl3): δ [ppm] = 12.9, 26.3, 26.4, 26.6, 26.7,
3
3
H), 2.11 (t, J1Ј,2Ј = 3.9, J1Ј,3Ј = 3.9 Hz, 1 H, 1Ј-H), 7.44–7.57 (m, CH2, C1Ј, C-c-Hex), 128.6, 128.8 (CH, o-/m-Ph), 132.8 (CH, p-Ph),
2 H, Ph-H), 7.96–7.98 (m, 2 H, o-Ph). 13C NMR (75 MHz, CDCl3): 138.7 (C , i-Ph), 200.5 (CO). IR (KBr) ν [cm–1] = 2978, 2886, 2843
˜
q
δ [ppm] = 12.2 (CH3, CH2CH3), 13.8 (CH3, 3Ј-CH3), 20.8 (CH2,
CH2CH3), 26.0 (CH, C3Ј), 33.4 (CH, C2Ј), 34.0 (CH, C1Ј), 127.8,
ν(Caliph–H), 1656 ν(C=O). C17H22O (242.16): calcd. C 84.25, H
9.15, found C 83.91, H 8.84. [α]2D0 = –9.0 (c = 0.57, CHCl3) at 95%
Eur. J. Org. Chem. 2005, 4571–4580
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4577