Rigid C3-Symmetric Scaffolds Based on Adamantane
[5] M. de Loos, J. H. van Esch, R. M. Kellogg, B. L. Feringa, Tet-
rahedron 2007, 63, 7285–7301.
[6] a) J. Van Gestel, A. R. A. Palmans, B. Titulaer, J. A. J. M. Vek-
emans, E. W. Meijer, J. Am. Chem. Soc. 2005, 127, 5490–5494;
b) M. L. Bushey, T.-Q. Nguyen, W. Zhang, D. Horoszewski, C.
Nuckolls, Angew. Chem. 2004, 116, 5562–5570; Angew. Chem.
Int. Ed. 2004, 43, 5446–5453.
[7] a) S. Fournel, S. Wieckowski, W. Sun, N. Trouche, H. Dumort-
ier, A. Bianco, O. Chaloin, M. Habib, J. C. Peter, P. Schneider,
B. Vray, R. E. Toes, R. Offringa, C. J. Melief, J. Hoebeke, G.
Guichard, Nat. Chem. Biol. 2005, 1, 377–382; b) H. Li, Y.
Guan, A. Szczepanska, A. J. Moreno-Vargas, A. T. Carmona,
I. Robina, G. K. Lewis, L. X. Wang, Bioorg. Med. Chem. 2007,
15, 4220–4228.
(10.3 mmol; 91%) of the amine 26 as a colorless oil. IR (film): ν
˜
= 3283, 2923, 2844, 1579, 1451, 1386, 1317, 818 cm–1. 1H NMR
3
(400 MHz, [D6]DMSO): δ = 2.35 (t, J = 7.0 Hz, 6 H), 1.91 (br. s,
1 H), 1.13–1.23 (m, 12 H), 0.92–1.02 (m, 12 H) ppm. 13C NMR
(100 MHz, [D6]DMSO): δ = 46.8, 42.9, 41.4, 41.0, 33.0, 29.0, 26.8
ppm. HR-MS (ESI): calcd. (MH+: C19H38N3) 308.3057, found
308.3060.
1,3,5-Tris[2-(methoxycarbonyl)ethyl]adamantane
(27):
6.5 mL
(13.0 mmol) of a 2 solution of (trimethylsilyl)diazomethane in
diethyl ether was added dropwise, at room temperature, to a solu-
tion of 1.00 g (2.8 mmol) of 23 in 20 mL of toluene/methanol (1:3).
The resulting suspension was stirred for 40 h at room temperature
and 0.5 mL acetic acid was added. The solvent was evaporated in
vacuo and the residue was dissolved in 100 mL of 1 aqueous
NaOH. The resulting suspension was extracted three times with
100 mL of dichloromethane. The combined extracts were dried
with Na2SO4, filtered and the solvent was removed in vacuo to give
[8]
[9]
G. Parkin, Chem. Rev. 2004, 104, 699–767.
a) R. Wyatt, J. Sodroski, Science 1998, 280, 1884–1888; b)
D. M. Eckert, P. S. Kim, Annu. Rev. Biochem. 2001, 70, 777–
810; c) D. W. Banner, A. D’Arcy, W. Janes, R. Gentz, H. J.
Schoenfeld, C. Broger, H. Loetscher, W. Lesslauer, Cell 1993,
73, 431–445.
0.70 g (1.8 mmol; 63%) of pure triester 27 as an oil. IR (film): ν =
˜
[10]
[11]
[12]
J. Rao, J. Lahiri, L. Isaacs, R. M. Weis, G. M. Whitesides, Sci-
ence 1998, 280, 708–711.
P. Misra, V. Humblet, N. Pannier, W. Maison, J. V. Frangioni,
J. Nucl. Med. 2007, 48, 1379–1389.
a) N. Weibel, L. Charbonniere, R. Ziessel, Tetrahedron Lett.
2006, 47, 1793–1796; b) P. R. Ashton, S. E. Boyd, C. L. Brown,
N. Jayaraman, S. A. Nepogodiev, J. F. Stoddart, Chem. Eur. J.
1996, 2, 1115–1128; c) G. R. Newkome, R. K. Behera, C. N.
Moorefield, G. R. Baker, J. Org. Chem. 1991, 56, 7162–7167.
a) D. S. Kemp, K. S. Petrakis, J. Org. Chem. 1981, 46, 5140–
5143; b) E. A. Jefferson, E. Locardi, M. Goodman, J. Am.
Chem. Soc. 1998, 120, 7420–7428.
2911, 2845, 1739, 1452, 1436, 1310, 1167 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 3.65 (s, 9 H), 2.24 (t, 3J = 8.3 Hz, 6 H),
3
2
2.09 (sept, J = 2.9 Hz, 1 H), 1.13 (d, J = 11.9 Hz, 3 H), 1.04 (d,
2J = 11.8 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 175.0,
51.7, 46.2, 40.9, 38.4, 33.4, 29.2, 28.2 ppm. HR-MS (EI): calcd.
(C22H34O6) 394.2355, found 394.2356.
1,3,5-Tris(3-hydroxypropyl)adamantane (28):
A solution of 27
(0.67 g, 1.70 mmol) in 15 mL dry THF was cooled to 0 °C and
LiAlH4 (0.58 g, 15.3 mmol) were added. The reaction mixture was
heated to reflux for 4 h and the resulting solution was poured on
ice/HCl. The aqueous phase was extracted three times with ethyl
acetate, the combined organic phases was washed with 1 NaOH
and water, dried with Na2SO4, filtered and the solvent was evapo-
rated in vacuo to give 0.52 g (1.67 mmol; 99%) of pure 28 as a
[13]
[14]
[15]
J. B. Bialecki, L.-H. Yuan, B. Gong, Tetrahedron 2007, 63,
5460–5469.
a) R. Welti, F. Diederich, Helv. Chim. Acta 2003, 86, 494–503;
b) K. H. Lee, J.-I. Hong, Tetrahedron Lett. 2000, 41, 6083–
6087; c) A. Vacca, C. Nativi, M. Cacciarini, R. Pergoli, S. Roe-
lens, J. Am. Chem. Soc. 2004, 126, 16456–16465; d) W. C. Still,
R. Liu, Philos. Trans. R. Soc. London, Ser. A 1993, 345, 97–
104.
colorless oil. IR (film): ν = 3289, 2920, 2840, 1449, 1055, 1011
˜
3
cm–1. 1H NMR (400 MHz, [D4]MeOH): δ = 3.35 (t, J = 6.8 Hz, 6
3
3
H), 2.07 (sept, J = 2.8 Hz, 1 H), 1.45–1.53 (m, 6 H), 1.38 (d, J =
2.8 Hz, 6 H), 1.11–1.22 (m, 12 H) ppm. 13C NMR (100 MHz, [D4]-
MeOH): δ = 64.0, 48.3, 42.7, 41.2, 34.4, 31.1, 26.9 ppm. HR-MS
(EI): calcd. (C19H34O3) 310.2508, found 310.2505.
[16]
a) A. Bianco, S. Fournel, S. Wieckowski, J. Hoebeke, G. Guich-
ard, Org. Biomol. Chem. 2006, 4, 1461–1463; b) J. Bitta, S. Ku-
bik, Org. Lett. 2001, 3, 2637–2640.
[17]
[18]
W. Maison, J. V. Frangioni, N. Pannier, Org. Lett. 2004, 6,
Supporting Information (see also the footnote on the first page of
4567–4569.
1
this article): H and 13C-NMR spectra of all new compounds.
Q. Li, C. Jin, P. A. Petukhov, A. V. Rukavishnikov, T. O. Zai-
kova, A. Phadke, D. H. LaMunyon, M. D. Lee, J. F. W. Keana,
J. Org. Chem. 2004, 69, 1010–1019.
Acknowledgments
[19]
a) M. V. Gil, M. J. Arevalo, O. Lopez, Synthesis 2007, 1589–
1620; b) D. Fournier, R. Hoogenboom, U. S. Schubert, Chem.
Soc. Rev. 2007, 36, 1369–1380; c) J. E. Moses, A. D. Moor-
house, Chem. Soc. Rev. 2007, 36, 1249–1262; d) V. D. Bock, H.
Hiemstra, J. H. van Maarseveen, Eur. J. Org. Chem. 2006, 51–
68; e) H. C. Kolb, M. G. Finn, K. B. Sharpless, Angew. Chem.
2001, 113, 2056–2075; Angew. Chem. Int. Ed. 2001, 40, 2004–
2021.
Review: I. K. Moiseev, N. V. Makarova, M. N. Zemtsova, Russ.
Chem. Rev. 1999, 68, 1001–1020.
H. Stetter, C. Wulff, Chem. Ber. 1960, 93, 1366–1371.
R. C. Fort, P. v. R. Schleyer, Chem. Rev. 1964, 64, 277–300.
Notable exceptions are: a) A. A. Fokin, P. R. Schreiner, Adv.
Synth. Catal. 2003, 345, 1035–1052; b) M. Ohno, K. Ishizaki,
S. Eguchi, J. Org. Chem. 1988, 53, 1285–1288.
We gratefully acknowledge support from the Deutsche Forschungs-
gemeinschaft (DFG) (MA 2529/3).
[1] a) S. E. Gibson, M. P. Castaldi, Chem. Commun. 2006, 3045–
3062; b) C. Moberg, Angew. Chem. 1998, 110, 260–281; Angew.
Chem. Int. Ed. 1998, 37, 228–268.
[2] a) S. E. Gibson, M. P. Castaldi, Angew. Chem. 2006, 118, 4834–
4837; Angew. Chem. Int. Ed. 2006, 45, 4718–4720.
[3] a) S. Bellemin-Laponnaz, L. H. Gade, Actualite Chimique 2007,
307, 16–20; b) G. Bringmann, R.-M. Pfeifer, C. Rummey, K.
Hartner, M. Breuning, J. Org. Chem. 2003, 68, 6859–6863; c)
T. Fang, J. Xu, D.-M. Du, Synlett 2006, 10, 1559–1563.
[4] a) F. Fabris, L. Pellizzaro, C. Zonta, O. De Lucchi, Eur. J. Org.
Chem. 2007, 283–291; b) G. Haberhauer, T. Oeser, F. Rominger,
Chem. Eur. J. 2005, 11, 6718–6726; c) M. C. Schopohl, C. Sier-
ing, O. Kataeva, S. R. Waldvogel, Angew. Chem. 2003, 115,
2724–2727; Angew. Chem. Int. Ed. 2003, 42, 2620–2623; d)
D. Q. McDonald, W. C. Still, J. Am. Chem. Soc. 1996, 118,
2073–2077; e) S.-G. Kim, K.-H. Kim, J. Jung, S. K. Shin, K. H.
Ahn, J. Am. Chem. Soc. 2002, 124, 591–596.
[20]
[21]
[22]
[23]
[24]
H. Stetter, C. Wulff, Chem. Ber. 1960, 93, 1366–1371. For an
alternative oxidation procedure see: R. Mello, L. Cassidei, M.
Fiorentino, C. Fusco, R. Curci, Tetrahedron Lett. 1990, 31,
3067–3070.
Y. Ishii, T. Nakano, N. Hirai, PCT Int. Appl. (1998), WO
9840337.
[25]
[26]
H. Newman, Synthesis 1972, 692–693.
Eur. J. Org. Chem. 2008, 1278–1284
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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