1796
S. Maas et al.
PAPER
Ethyl 2-Cyano-3,4-dimethylpentanoate (5a)
Colorless oil; Rf 0.32 (PE/EtOAc, 10:1); mixture of diastereomers.
1H NMR: d = 0.85 and 1.01 each (d, 3 H, J = 6.8 Hz, 3-CH3), 0.93
[m, 6 H, CH(CH3)2], 1.62 (m, 1 H, H-3), 1.91 (m, 1 H, H-4), 3.35
and 3.60 each (d, 1 H, J = 4.7 and 7.6 Hz, CHCO2Et].
13C NMR: d = 13.4, 13.9 (CH3CH2O), 42.1, 42.7 (CHCO2Et), 62.4,
62.5 (CH2O), 115.4, 116.1 (CN), 165.9, 166.4 (C=O).
Ethyl 2-Cyano-3,4,4-trimethylpentanoate (5b)21
Colorless oil; Rf 0.35 (PE/EtOAc, 10:1); mixture of diastereomers.
1H NMR: d = 0.94, 0.95 each [s, 9 H, C(CH3)3], 1.06 (d, 3 H,
J = 7.0 Hz, CH3CH), 1.99 and 2.12 each (dq, 1 H, J = 2.1 and 5.0
Hz, CHBu-t), 3.47 and 3.66 each (d, 1 H, J = 2.1 and J = 5.0 Hz,
CHCO2Et).
13C NMR: d = 27.4, 27.6 C(CH3) 3, 33.4, 33.9 C(CH3) 3, 39.8, 40.4
(CHBu-t), 43.8, 44.7 (CHCO2Et), 62.4, 62.7 (CH2O), 116.1, 117.4
(CN), 166.4, 167.0 (C=O).
1H NMR: d = 0.91 (t, 3 H, J = 7.3 Hz, CH3CH2), 1.09 [s, 3 H,
(CH3)2C], 1.59 [s, 3 H, (CH3)2C], 3.62 (m, 1 H, CHPh), 3.70 [d, 1
H, J = 3.2 Hz, CH(CO)2], 7.15–7.31 (m, 5 H, C6H5).
13C NMR: d = 12.4 (CH3), 25.6 (CH2CH3), 27.9, 28.3 [C(CH3)2],
48.1 (CHPh), 50.9 [CH(CO)2], 105.3 (CMe2), 139.5 (C-ipso, C6H5),
164.6, 165.8 (C=O).
2,2-Dimethyl-5-(1-ethyl-2-methylpropyl)-1,3-dioxane-4,6-
dione (11b)
Separated from 12b by flash chromatography; yield: 63%; colorless
crystals; mp 54°C (PE/EtOAc); Rf 0.14 (PE/EtOAc, 10:1).
1H NMR: d = 0.86–0.97 (m, 9 H, CH3), 1.73 [s, 6 H, (CH3)2C], 2.18
(m, 1 H, CHEt), 3.49 [d, 1 H, J = 2.5 Hz, CH(CO)2].
13C NMR: d = 15.1, 20.9, 21.3 (CH3), 23.3 (CH2), 27.6, 28.1
[C(CH3)2], 30.2 (CHMe2), 46.2 (CHEt), 47.9 [CH(CO)2], 104.7
(CMe2), 166.1 (C=O).
2,2-Dimethyl-5-(2-methylpropyl)-1,3-dioxane-4,6-dione (12b)22
Separated from 11b; yield: 23%; colorless crystals; mp 120°C
(PE/EtOAc); Rf 0.18 (PE/EtOAc, 10:1).
1H NMR: d = 0.89 (d, 6 H, J = 6.4 Hz, CH3), 1.70 [s, 3 H, (CH3)2C],
1.75 [s, 3 H, (CH3)2C], 1.92–2.07 (m, 3 H, CH2, CHMe2), 3.42 [t, 1
H, J = 5.4 Hz, CH(CO)2].
(1,2-Dimethylpropyl)malonodinitrile (6)
Colorless oil; Rf 0.26 (PE/EtOAc, 10:1).
1H NMR: d = 0.93–1.01 [m, 6 H, CH(CH3)2], 1.20 (d, 3 H, J = 5.6
Hz, CHCH3), 3.75 [dd, 1 H, 3J = 5.6 Hz, 4J = 1.2 Hz, CH(CN)2].
13C NMR: d = 13.5, 18.0, 20.6 (CH3), 27.5 (CHMe2), 30.4 (C-b),
41.4 (CCN), 111.9, 112.8 (CN).
2,2-Dimethyl-5-(1-phenylethyl)1,3-dioxane-4,6-dione(8a)22
Yield: 88%; colorless crystals; mp 101°C (); Rf 0.25 (PE/EtOAc,
10:1).
1H NMR: d = 3.68 [d, 1 H, J = 3.2 Hz, CH(CO)2], 3.98 (dq, 1 H,
J = 7.3, 3.0 Hz, CHPh), 7.20–7.34 (m, 5 H, C6H5).
13C NMR: d = 22.1 (CH3), 25.9 (CHMe2), 26.8, 28.6 [C(CH3)2],
44.2 [CH(CO)2], 35.3 (CH2), 104.8 (CMe2), 166.0 (C=O).
Ethyl 2-Cyano-3-ethyl-4-methylpentanoate (13a)
Colorless oil; mixture of diastereomers; Rf 0.30 (PE/EtOAc, 10:1).
1H NMR: d = 0.87–0.97 (m, 9 H, CH3) 1.25–1.95 (m, 4 H, CHEt,
CH2, CHMe2), 3.59 and 3.60 each (d, 1 H, J = 5.4 and 6.8 Hz,
CHCO2Et).
13C NMR: d = 11.9, 12.1 (CH3), 13.9 (CH3CH2O), 18.5, 19.2 (CH3),
20.2, 21.2 (CH3), 21.5, 22.6 (CH2), 39.5, 40.3 (CHEt), 46.7, 46.8
(CHCO2Et), 62.5, 62.6 (CH2O), 115.9, 116.1 (CN), 166.8, 167.0
(C=O).
13C NMR: d = 17.8 (CH3), 28.0, 28.3 [C(CH3)2], 38.7 (CHPh),
105.2 [C(CH3)2], 164.7, 165.0 (C=O).
2,2-Dimethyl-5-(1,2-dimethylpropyl)-1,3-dioxane-4,6-dione
(8b)
Yield: 93%; colorless crystals; mp 89°C (PE/EtOAc); Rf 0.18 (PE/
EtOAc, 10:1).
Ethyl 2-Cyano-3-ethyl-4,4-dimethylpentanoate (13b)
Colorless oil; mixture of diastereomers; Rf 0.35 (PE/EtOAc, 10:1).
1H NMR: d = 0.89 [d, 3 H, J = 7.1 Hz, CH(CH3)2], 0.91 [d, 3 H,
J = 6.7 Hz, CH(CH3)2], 1.00 (d, 3 H, J = 6.7 Hz, CH3), 1.69 and
1.70 each [s, 3 H, C(CH3)2], 2.02 (m, 1 H, CHMe2), 2.16 (m, 1 H,
CHCH3), 3.55 [d, 1 H, J = 2.9 Hz, CH(CO)2].
13C NMR: d = 15.1, 20.9, 21.3, (CH3), 27.8, 28.2 [C(CH3)2], 41.3
(CHMe), 48.8 [CH(CO)2], 104.6 (CMe2), 164.7, 166.3 (C=O).
1H NMR: d = 0.87 (t, 3 H, J = 7.5 Hz, CH3), 0.96 and 0.97 each [s,
9 H, C(CH3)3], 1.53–1.75 (m, 2 H, CH2), 1.89–1.95 (m, 1 H, CHBu-
t), 3.61 and 3.69 each (d, 1 H, J = 1.0 and 3.0 Hz, CHCO2Et).
13C NMR: d = 13.1, 13.2 (CH3). 13.8, 13.9 (CH3CH2O) 20.9, 21.7
(CH2), 27.8, 28.0 [C(CH3)3], 34.0, 34.4 (CMe3), 37.8, 38.5 (CHBu-
t), 50.7, 51.3 (CHCO2Et), 62.6, 62.7 (CH2O), 116.2, 116.6 (CN),
167.4, 167.6 (C=O).
Diethyl (1-Methylpropyl)malonate (9a)
Identical to 4b; Rf 0.49 (PE/EtOAc, 10:1).
Diethyl (1-Ethylpropyl)malonate (9b)23
Ethyl 2-Cyano-3,3-dimethylpentanoate (13c)
Colorless oil; Rf 0.35 (PE/EtOAc, 10:1).
1H NMR: d = 0.86 (t, 3 H, CH2CH3),1.04 (s, 3 H, CH3), 1.08 (s, 3 H,
CH3), 1.46 (m, 2 H, CH2), 3.31 (s, 1 H, CHCO2Et).
13C NMR: d = 8.1 (CH3CH2C) 14.0 (CH3CH2O), 24.1, 24.7 (CH3),
33.0 (CH2), 37.7 (EtCMe2), 47.8 (CHCO2Et), 62.3 (CH2O), 116.0
(CN), 165.4 (C=O).
Colorless oil; Rf 0.55 (PE/EtOAc, 10:1).
1H NMR: d = 0.83 (t, 6 H, J = 7.5 Hz, CH3CH2CH), 2.00 (m, 1 H,
CHEt2), 3.34 [d, 1 H, J = 8.1 Hz, CH(CO2Et)2].
13C NMR. d = 10.8 (CH3), 14.0 (CH3CH2O), 23.0 (CH2), 40.9
(CHEt2), 55.1 [CH(CO2Et)2], 60.9 (CH2O), 169.0 (C=O).
Diethyl (1-Phenylpropyl)malonate (9g)24
Colorless oil; Rf 0.60 (PE/EtOAc, 5:1).
Ethyl 2-Cyano-3-ethyl-3-methylpentanoate (13d)
Colorless oil; Rf 0.41 (PE/EtOAc, 10:1).
1H NMR: d = 0.83 (t, 3 H, J = 7.6 Hz, CH3CH2), 0.84 (t, 3 H, J = 7.3
Hz, CH3CH2), 1.04 (s, 3 H, CH3), 1.39 (dq, 2 H, J = 7.5, 1.7 Hz,
CH2), 1.50 (q, 2 H, J = 7.5 Hz, CH2), 3.41 (s, 1 H, CHCO2Et).
13C NMR: d = 7.6, 7.8 [(CH3CH2)2C] 13.9 (CH3CH2O), 21.7 (CH3),
28.8 (CH2), 29.5 (CH2), 40.3 (Et2CMe), 46.1 (CHCO2Et), 62.2
(CH2O), 116.1 (CN), 165.5 (C=O).
1H NMR: d = 0.68 (t, 3 H, J = 6.0 Hz, CH3CH2CH), 3.22 (dt, 1 H,
J = 3.7, 10.9 Hz, CHPh), 3.60 [d, 1 H, J = 11.0 Hz, CH(CO2Et)2],
3.84 (q, 2 H, J = 7.1 Hz, CH2O), 4.19 (q, 2 H, J = 7.1 Hz, CH2O),
7.11–7.26 (m, 5 H, C6H5).
13C NMR: d = 11.7 (CH3), 13.6, 14.1 (CH3CH2O), 47.3 (CHPh),
61.0, 61.4 (CH2O), 140.6 (C-ipso, C6H5), 167.8, 168.5 (C=O).
Ethyl 2-Cyano-3-ethyl-3,4-dimethylpentanoate (13e)
Colorless oil; mixture of diastereomers; Rf 0.43 (PE/EtOAc, 10:1).
2,2-Dimethyl-5-(1-phenylpropyl)-1,3-dioxane-4,6-dione (11a)
Yield: 83%; colorless oil; Rf 0.46 (PE/EtOAc, 5:1).
Synthesis 1999, No. 10, 1792–1798 ISSN 0039-7881 © Thieme Stuttgart · New York