4ꢀArylꢀ1,7ꢀdihydroxyalkaneꢀ2,6ꢀdiones
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 3, March, 2016
719
(dd, 1 H, CH2, J = 18.2 Hz, J = 3.6 Hz); 3.54 (q, 1 H, CH,
J = 7.0 Hz); 4.98, 5.16 (both s, in a 1 : 2 intensity ratio, 2 H, OH);
7.10 (q, 1 H, Ph, J = 4.0 Hz); 7.21 (d, 4 H, Ph, J = 3.6 Hz).
13C NMR (DMSOꢀd6), δ: 20.55, 20.71, 24.96 (all CH2), 25.99,
26.12 (both Me); 32.67, 32.77 (both CH2); 34.73 (CH), 41.9,
42.01 (both CH2), 75.75, 76.94 (both CO), 126.82, 127.44, 127.92
(all CH, Ph), 144.98 (C, Ph), 213.89, 214.27 (both C=O). ME,
(ESI), m/z: 355 [M + Na]+, 356 [M + H + Na]+. Ketodiol 3i
was also isolated in 18% yield from the reaction mixture obtained
by the reaction of enone 2a and methyl ketone 1b (method A).
Synthesis of diketo diacetates 4 (general procedure). To
a solution of the corresponding diketo diol 3 (1 mmol) in CH2Cl2
(15—20 mL) containing trimethylamine (2 mL) and 4ꢀdimethylꢀ
aminopyridine (2 mg), acetic anhydride (0.6 mL) was added
dropwise, the reaction mixture was maintained at 20—25 °C for
2 days, and then gently refluxed for 30 min. The reaction mixꢀ
ture was suspended in an iceꢀcold aqueous NaHCO3 and exꢀ
tracted with benzene—ethyl acetate. The organic layer was filꢀ
tered through a silica gel pad (a 3 cm thick). The target acetates
were isolated as described in method A.
The reaction mixture was refluxed for 5—7 h, cooled, and
the solvent was removed in vacuo. The semiꢀdry residue was
triturated with ethyl acetate—hexane. Solid oximes were reꢀ
crystallized.
1,5ꢀBis(1ꢀhydroxycyclohexyl)ꢀ3ꢀphenylpentaneꢀ1,5ꢀdione diꢀ
oxime (5b). Yield 67%, m.p. 179 °C (hexane—EtOAc, 1 : 2).
Found (%): C, 68.47; H, 6.39; N, 6.58. C23H34N2O4. Calculatꢀ
ed (%): C, 68.63; H, 8.51; N, 6.96. IR, ν/cm–1: 3540, 3360,
3212, 1648. 1H NMR (300 MHz, DMSOꢀd6—CDCl3 (1 : 4)), δ:
1.03, 1.14—1.65 (both m, 2 H and 18 H, CH2); 2.36 (br.s, 2 H,
overlaps with the OH group proton); 2.42, 2.89 (both ABX sysꢀ
tem, 2 H each, CH2, JAB = 12.8 Hz, JAX = 4.4 Hz, JBX = 6.8 Hz);
3.72 (q, 1 H, CH, J = 7.5 Hz); 7.06—7.22 (m, 5 H, Ph); 9.58
(br.s, 2 H, NOH). 13C NMR (DMSOꢀd6—CDCl3 (1 : 4)), δ:
21.39, 21.48, 25.33, 31.61, 35.45, 35.81 (all CH2), 39.59 (CH),
73.58 (CO), 126.46, 127.95, 128.05 (all CH, Ph); 145.30 (C, Ph);
163.39 (C=N). MS, m/z (Irel (%)): 403 [M + H]+ (2), 402 [M]+
(13), 385 (17), 384 (24), 367 (16), 352 (14), 319 (18), 269 (100),
229 (18), 228 (33), 226 (19), 171 (24), 139 (19), 131 (27), 130
(67), 124 (23), 122 (25), 103 (20), 99 (82), 98 (36), 81 (62), 69
(20), 55 (78), 43 (20).
1,5ꢀBis(1ꢀhydroxycyclohexyl)ꢀ3ꢀ(4ꢀmethylphenyl)pentaneꢀ1,5ꢀ
dione dioxime (5c). Yield 46%, m.p. 166—167 °C (EtOH—EtOAc,
1 : 3). Found (%): C, 69.06; H, 8.62; N, 6.54. C24H36N2O4.
Calculated (%): C, 69.20; H, 8.71; N, 6.73. IR, ν/cm–1: 3560,
3360, 3228, 1652, 1636. 1H NMR (500 MHz, DMSOꢀd6), δ:
1.06, 1.22, 1.37, 1.49 (all m, 2 H, 4 H, 4 H, 10 H, CH2); 2.23
(s, 3 H, Me); 2.54, 2.68 (both ABX system, 2 H each, CH2,
JAB = 13.2 Hz, JAX = 8.2 Hz, JBX = 7.3 Hz); 3.94 (q, 1 H, CH,
J = 7.6 Hz); 4.19 (s, 2 H, OH); 7.02, 7.13 (both d, 2 H each, ArH,
J = 8.2 Hz); 10.32 (s, 2 H, NOH). MS, (ESI), m/z: 439
[M + Na]+, 455 [M + К]+.
2,8ꢀDiacetoxyꢀ2,8ꢀdimethylꢀ5ꢀphenylnonaneꢀ3,7ꢀdione (4a).
Yield 82%, m.p. 114—115 °C (hexane—EtOAc, 1 : 1). Found (%):
C, 67.02; H, 7.41. C21H28O6. Calculated (%): C, 67.00; H, 7.50.
IR, ν/cm–1: 1738, 1707 sh., 1256 (C—O). 1H NMR (300 MHz,
CDCl3), δ: 1.28, 1.37 (both s, 6 H each, Me); 2.06 (s, 6 H,
MeCO); 2.81, 2.91 (both ABX system, 2 H each, CH2, JAB
=
= 18.0 Hz, JAX = 8.0 Hz, JBX = 6.0 Hz); 3.74 (q, 1 H, CH,
J = 6.8 Hz); 7.14—7.29 (m, 5 H, Ph). 13C NMR (DMSOꢀd6), δ:
20.83, 22.65, 22.83, 35.28, 41.30, 82.82, 126.09, 127.62, 127.91,
144.00, 169.81, 206.47. MS, m/z (Irel (%)): 376 [M]+ (1), 316
(26), 276 (20), 275 (50), 256 (24), 216 (22), 215 (74), 187 (26),
145 (24), 132 (23), 131 (100), 117 (24), 104 (73), 100 (68), 71 (31),
70 (43), 69 (61), 59 (74), 43 (37).
Author is grateful to A. A. Vasil´ev and A. S. Shashkov
(N. D. Zelinsky Institute of Organic Chemistry RAS) for
help in writing this article and especially for fruitful disꢀ
cussion of spectral data.
1,5ꢀBis(1ꢀacetoxycyclohexyl)ꢀ3ꢀphenylpentaneꢀ1,5ꢀdione
(4b). Yield 79%, m.p. 116 °C (hexane—EtOAc, 1 : 1). Found (%):
C, 70.83; H, 7.94. C27H36O6. Calculated (%): C, 71.02; H, 7.95.
IR, ν/cm–1: 1736, 1702. 1H NMR (300 MHz, DMSOꢀd6),
δ: 1.12, 1.34, 1.51, 1.67, 1.82 (all m, 4 H, 6 H, 6 H, 2 H, 2 H,
CH2); 2.06 (s, 6 H, Ac); 2.69, 2.81 (both ABX system, 2 H each,
CH2, JAB = 17.8 Hz, JAX = 6.1 Hz, JBX = 7.9 Hz); 3.53 (q, 1 H,
CH, J = 6.7 Hz); 7.13 (q, 1 H, Ph, J = 3.6 Hz); 7.20, 7.22
(both s, 2 H, Ph). 13C NMR (DMSOꢀd6), δ: 20.55, 20.64, 20.72,
24.32, 29.57, 30.24, 35.17, 41.32, 84.24, 126.01, 127.63, 127.88,
144.13, 169.78, 206.79. MS, (ESI), m/z: 479 [M + Na]+, 480
[M + H + Na]+.
2,8ꢀDiacetoxyꢀ2,8ꢀdimethylꢀ5ꢀ(4ꢀmethoxyphenyl)nonaneꢀ
3,7ꢀdione (4d). Yield (80%), m.p. 112 °C (hexane—EtOAc, 1 : 1).
Found (%): C, 65.10; H, 7.63. C22H30O7. Calculated (%):
C, 65.01; H, 7.44. IR, ν/cm–1: 1738, 1706. 1H NMR (300 MHz,
DMSOꢀd6), δ: 1.15, 1.27, 2.01 (all s, 6 H each, Me); 2.68—2.75
(m, 4 H, CH2), 3.49 (br.t, 1 H, CH, J = 6.0 Hz); 3.69 (s, 3 H,
Me); 6.78, 7.14 (both d, 2 H each, ArH, J = 8.6 Hz). 13C NMR
(DMSOꢀd6), δ: 20.84, 22.66, 22.86, 34.51, 41.49, 54.83, 82.87,
113.31, 128.58, 135.92, 157.57, 169.83, 206.55. MS, m/z (Irel (%)):
407 [M + H]+ (8), 406 [M]+ (63), 346 (13), 305 (19), 292 (39),
287 (16), 286 (41), 263 (15), 246 (17), 245 (30), 216 (22), 203 (43),
175 (72), 161 (16), 134 (46), 129 (28), 101 (48), 91 (100).
Synthesis of dioximes 5 (general procedure). To a stirred soꢀ
lution of the corresponding diketo diol 3 (1—2 mmol) and
NH2OH•HCl (0.49 g, 7 mmol) in aqueous (1 : 4) MeOH
(20 mL), NaOH (0.3 g) was added in one portion at 28—30 °C.
References
1. (a) C. H. Heathcock, in Comprehensive Organic Synthesis,
Eds B. M. Trost, I. Fleming, NewꢀYork, 1993, Vol. 2, Part 2,
p. 133; (b) R. H. Wiley, Org. Synth., Coll. Vol. 3, 1995, 853;
(c) J.ꢀC. Plaquevent, D. Cahard, F. Guillen, Sci. Synth.,
2004, 26, 513; (d) Modern Aldol Reactions, Ed. R. Mahrwald,
Wiley—VCH, Weinheim, 2004.
2. (a) A. L. Marzinzik, E. R. Felder, J. Org. Chem., 1998, 63,
723; (b) V. Henryon, L. W. Liu, R. Lopez, J. Prunet, J. P.
Ferezou, Synthesis, 2001, 2401; (c) R. Antonioletti, P. Boviꢀ
celli, S. Malancona, Tetrahedron, 2002, 58, 589; (d) C. Siꢀ
mon, T. Constantieux, J. Rodriguez, Eur. J. Org. Chem.,
2004, 4957; (e) V. Cadierno, J. Diez, S. E. GarciaꢀGarrido,
J. Gimeno, N. Nebra, Adv. Synt. Catal., 2006, 348, 2125;
(f) H.ꢀM. F. Madkour, A. S. Elgazwy, Curr. Org. Chem.,
2007, 11, 853.
3. (a) H.ꢀC. Guo, J.ꢀA. Ma, Angew. Chem., Int. Ed., 2006, 45,
354; (b) N. Krause, A. HoffmanꢀRoder, Synthesis, 2001, 171;
(c) Domino Reactions in Organic Synthesis, Eds L. F. Tietze,
G. Brasche, К. M. Gericke, WileyꢀWCH, Weinheim,
2006, 631 pp.