PAPER
Stereospecific Synthesis of Substituted Cyclopropanes
1475
and the filtrate was concentrated under vacuum to give the crude
product, which was used in the next step.
4-(Diethoxyphosphoryloxy)octanenitrile (10)
Yield: 85%; colorless oil; Rf = 0.33 (CHCl3–acetone, 90:10).
IR (film): 2225 cm–1.
Ethyl 4-Hydroxyoctanoate (6)
1H NMR (CDCl3): d = 0.92 (t, J = 7.0 Hz, 3 H, CH3), 1.35 (dt,
J = 7.0 Hz, 4JP,H = 0.50 Hz, 6 H, 2 × CH3CH2OP), 1.36–1.48 (m, 2
H, CH2), 1.54–1.75 (m, 2 H, CH2), 1.91–2.03 (m, 2 H, CH2), 2.51
(t, J = 7.5 Hz, 2 H, CH2), 4.12 (dq, 3JP,H = 7.2 Hz, 3JH,H = 7.0 Hz, 2
H, CH3CH2OP), 4.14 (dq, JP,H = 7.2 Hz, JH,H = 7.0 Hz, 2 H,
CH3CH2OP), 4.37–4.45 (m, 1 H, CH).
Yield; 95%; colorless oil.
IR (film): 1748 cm–1.
1H NMR (CDCl3): d = 0.87 (t, J = 6.7 Hz, 3 H, CH3), 1.22 (t, J = 7.0
Hz, 3 H, CH3CH2O), 1.27–1.40 (m, 4 H, 2 × CH2), 1.45–1.70 (m, 2
H, CH2), 1.80–2.04 (m, 3 H, CH2, OH), 2.25 (t, J = 7.2 Hz, 2 H,
CH2), 4.10 (q, J = 7.0 Hz, 2 H, CH3CH2O), 4.15–4.26 (m, 1 H, CH).
13C NMR (CDCl3): d = 13.87 (CH3), 14.08 (CH3CH2O), 22.12
(CH2), 23.89 (CH2), 28.15 (CH2), 29.00 (CH2), 32.69 (CH2), 60.22
(CH3CH2O), 69.40 (CH), 172.93 (C=O),
3
3
13C NMR (CDCl3): d = 13.23 (CH3), 13.84 (CH2), 16.10 (d,
3JC,P = 6.8 Hz, 2 × CH3CH2OP), 22.39 (CH2), 26.86 (CH2), 30.91 (d,
3
3JC,P = 4.8 Hz, CH), 34.59 (d, JC,P = 3.2 Hz, CH2), 63.92 (d,
2JC,P = 7.0 Hz, 2 × CH3CH2OP), 77.34 (CH2), 119.30 (CN).
31P NMR (CDCl3): d = –1.20.
4-Hydroxyoctanenitrile (7)11
Yield: 95%; colorless oil.
1H NMR (CDCl3): d = 0.90 (t, J = 7.0 Hz, 3 H, CH3), 1.22–1.48 (m,
6 H, 3 × CH2), 1.67–1.80 (m, 2 H, CH2), 2.00 (br s, 1 H, OH), 2.48
(t, J = 7.2 Hz, 2 H, CH2), 3.63–3.74 (m, 1 H, CH).
Anal. Calcd for C8H15NO: C, 68.04; H, 10.71; N, 11.25. Found: C,
68.24; H, 10.66; N, 11.29.
Diethyl 3-(Diethoxyphosphoryloxyheptanephosphonate (11)
Yield: 82%; colorless oil; Rf = 0.15 (CHCl3–acetone, 80:20).
IR (film): 1242, 1032 cm–1.
Diethyl 3-(Hydroxy)heptanephosphonate (8)
1H NMR (CDCl3): d = 0.90 (t, J = 7.0 Hz, 3 H, CH3), 1.33 (t, J = 7.0
Hz, 6 H, 2 × CH3CH2OP), 1.34 (t, J = 7.0 Hz, 6 H, 2 × CH3CH2OP),
1.57–1.70 (m, 4 H, 2 × CH2), 1.79–1.92 (m, 2 H, CH2), 4.16 (dq,
3JH,H = 3JP,H = 7.0 Hz, 8 H, 4 × CH3CH2OP), 4.34–4.42 (m, 1 H,
CH).
Yield: 96%; pale-yellow oil.
IR (film): 1224, 1032 cm–1.
1H NMR (CDCl3): d = 0.90 (t, J = 6.7 Hz, 3 H, CH3), 1.33 (t, J = 7.0
Hz, 6 H, 2 × CH3CH2OP), 1.57–1.76 (m, 4 H, 2 × CH2), 1.79–1.92
(m, 3 H, CH2, OH), 4.18 (dq, JH,H = 3JP,H = 7.0 Hz, 4 H, 2 ×
3
3
13C NMR (CDCl3): d = 12.94 (CH3), 15.11 (d, JC,P = 6.7 Hz, 2 ×
CH3CH2OP), 4.20–4.29 (m, 1 H, CH).
3
CH3CH2OP), 15.40 (d, JC,P = 6.0 Hz, 2 × CH3CH2OP), 20.16 (d,
13C NMR (CDCl3): d = 12.94 (CH3), 15.97 (d, JC,P = 6.0 Hz, 2 ×
3
1JC,P = 143.2 Hz, PCH2), 21.48 (CH2), 23.48 (CH2), 26.83 (CH2),
30.58 (CH), 33.72 (d, 2JC,P = 3.80 Hz, CH2), 60.83 (d, 2JC,P = 6.5 Hz,
2 × CH3CH2OP), 62.78 (d, 2JC,P = 5.8 Hz, 2 × CH3CH2OP), 78.19
(dd, 3JC,P = 18.5 Hz, 2JC,P = 6.30 Hz, PCH).
CH3CH2OP), 20.34 (d, 1JC,P = 144.7 Hz, PCH2), 21.41 (CH2), 23.86
2
(CH2), 26.57 (CH2), 30.58 (CH), 33.61 (d, JC,P = 3.9 Hz, CH2),
62.78 (d, 2JC,P = 7.0 Hz, 2 × CH3CH2OP), 71.08 (d, 3JC,P = 17.2 Hz,
CH).
31P NMR (CDCl3): d = 32.30, –1.20.
31P NMR (CDCl3): d = 31.21.
Anal. Calcd for C15H34O7P2: C, 46.39; H, 8.82. Found: C, 46.17; H,
8.78.
Phosphates 9, 10, and 11; General Procedure
To a solution of a corresponding alcohol 6, 8, or 9 (3 mmol) in
CH2Cl2 (10 mL) were added Et3N (0.63 mL, 4.5 mmol) and diethyl
chlorophosphite (0.64 g, 4.2 mmol) at 0 °C. The reaction mixture
was stirred for 2 h at r.t. Then 2 M N2O4 in CH2Cl2 (2.1 mL, 9 mmol)
was added at 0 °C. The stirring was continued for 20 h at r.t. Et2O
(10 mL) was added, the solid formed was collected by filtration, and
the filtrate was evaporated. The residue was purified by column
chromatography (eluent: CHCl3–acetone 90:10).
Cyclopropanes 12, 13, and 14; General Procedure
To a suspension of NaH (0.072g, 3 mmol) in THF (10 mL) was add-
ed the ester 9, 10, or 11 (3 mmol) at r.t. and the mixture was stirred
at reflux for 5 h. H2O (5 mL) was added and THF was evaporated
under reduced pressure. The residue was extracted with Et2O
(3 × 10 mL) and dried (MgSO4). Evaporation of the solvent afford-
ed crude product, which was purified by column chromatography.
Ethyl trans-n-Butylcyclopropanecarboxylate (12)7
Yield: 75%; colorless oil; Rf = 0.63 (CHCl3).
Ethyl 4-(Diethoxyphosphoryloxy)octanoate (9)
Yield: 88%; colorless oil; Rf = 0.30 (CHCl3–acetone, 90:10).
1H NMR (CDCl3): d = 0.68 (ddd, 3J = 9.7 Hz, 3J = 5.7 Hz, 2J = 4.0
Hz, 1 H, CHH), 0.89 (t, 3J = 6.7 Hz, 3 H, CH3), 1.11–1.17 (m, 1 H,
CHH), 1.26 (t, 3J = 7.2 Hz, 3 H, CH3CH2O), 1.30–1.38 (m, 8 H, CH,
CH, 3 × CH2), 4.11 (q, 3J = 7.2 Hz, 2 H, CH2O).
IR (film): 1764, 1254, 1024 cm–1
.
1H NMR (CDCl3): d = 0.90 (t, J = 6.7 Hz, 3 H, CH3), 1.26 (t, J = 7.0
Hz, 3 H, CH3CH2O), 1.34 (t, J = 7.2 Hz, 6 H, 2 × CH3CH2OP),
1.30–1.40 (m, 4 H, 2 × CH2), 1.48–1.70 (m, 2 H, CH2), 1.80–2.16
(m, 2 H, CH2), 2.45 (t, J = 7.5 Hz, 2 H, CH2), 4.11 (dq,
(1S,2S)-12
3JP,H = 3JH,H = 7.2 Hz,
2
H, CH3CH2OP), 4.12 (dq,
[a]D20 +72.2 (c = 1.00, CHCl3).
3JP,H = 3JH,H = 7.2 Hz, 2 H, CH3CH2OP), 4.13 (q, 3JH,H = 7.0 Hz, 2
H, CH3CH2O), 4.34–4.46 (m, 1 H, CH).
(1R,2R)-12
13C NMR (CDCl3): d = 13.74 (CH3), 14.02 (CH3CH2O), 15.90
(CH3CH2OP), 16.01 (CH3CH2OP), 22.34 (CH2), 26.80 (CH2),
29.62 (CH2), 29.86 (d, 3JP,C = 4.9 Hz, CH2), 34.63 (d, 3JP,C = 3.7 Hz,
CH2), 60.22 (CH3CH2O), 63.41 (d, 2JP,C = 6.0 Hz, 2 × CH3CH2OP),
78.40 (d, 2JP,C = 6.2 Hz, CH), 172.93 (C=O).
[a]D20 –64.7 (c = 1.00, CHCl3).
trans-2-n-Butylcyclopropanenitrile (13)
Yield: 72%; colorless oil; Rf = 0.38 (CHCl3).
IR (film): 2225 cm–1.
1H NMR (CDCl3): d = 0.87–1.14 (m, 5 H, CH3, CH2), 1.24–1.54 (m,
8 H, 3 × CH2, 2 × CH).
31P NMR (CDCl3): d = –1.18.
Anal. Calcd for C14H29O6P: C, 51.84; H, 9.01. Found: C, 51.94; H,
9.05.
Synthesis 2009, No. 9, 1473–1476 © Thieme Stuttgart · New York