PAPER
Ring-Opening of a Cyclic 1,2-p-Methoxybenzylidene Acetal
1251
mL) were added successively a soln of NaH2PO4 (62 mg, 0.397
mmol) in H2O (0.5 mL), 2-methyl-2-butene (0.15 mL, 1.42 mmol),
and NaClO2 (80%, 94 mg, 0.831 mmol). The mixture was stirred at
r.t. for 3 h, and then concentrated under reduced pressure. The re-
sulting oil was dissolved in CH2Cl2, dried over MgSO4, and concen-
trated. The crude product was purified by column chromatography
on silica gel (cyclohexane–EtOAc, 1:2) to give the carboxylic acid
1a.
(2) For some representative examples, see: (a) Han, H.; Yoon,
J.; Janda, K. D. J. Org. Chem. 1998, 63, 2045.
(b) Hennings, D. D.; Williams, R. M. Synthesis 2000, 1310.
(c) Davies, S. G.; Epstein, S. W.; Garner, A. C.; Ichihara, O.;
Smith, A. D. Tetrahedron: Asymmetry 2002, 13, 1555.
(d) Sasaki, Y.; Niida, A.; Tsuji, T.; Shigenaga, A.; Fujii, N.;
Otaka, A. J. Org. Chem. 2006, 71, 4969. (e) Kandula, S. R.
V.; Kumar, P. Tetrahedron 2006, 62, 9942. (f) Abraham,
E.; Davies, S. G.; Millican, N. L.; Nicholson, R. L.; Roberts,
P. M.; Smith, A. D. Org. Biomol. Chem. 2008, 6, 1655.
(3) Lee, J. H.; Yang, M. S.; Kang, K. Y.; Moon, Y. H.; Park, K.
H. Biosci. Biotechnol. Biochem. 2004, 68, 714.
(4) (a) McCoull, W.; Davis, F. A. Synthesis 2000, 1347.
(b) Osborn, H. M. I.; Sweeney, J. Tetrahedron: Asymmetry
1997, 8, 1693.
(5) (a) Davoli, P.; Moretti, I.; Prati, F.; Alper, H. J. Org. Chem.
1999, 64, 518. (b) Mahadevan, V.; Getzler, U. D. Y. L.;
Coates, G. W. Angew. Chem. Int. Ed. 2002, 41, 2781.
(6) Andersson, P. G.; Guijarro, D.; Tanner, D. J. Org. Chem.
1997, 62, 7364.
Yield: 47 mg (44%); colorless oil; Rf = 0.15 (cyclohexane–EtOAc,
1:2); [a]D25 +38.9 (c 2.03, CHCl3).
1H NMR (400 MHz, CDCl3): d = 7.30–7.19 (m, 12 H, CHarom),
6.78–6.76 (m, 2 H, CHarom), 4.78 (d, J = 11.4 Hz, 1 H, CHaHbAr),
4.44 (d, J = 11.4 Hz, 1 H, CHaHbAr), 4.36 [d, J = 13.1 Hz, 2 H,
N(CHaHbPh)2], 3.70 (s, 3 H, OCH3), 3.62 (d, J = 3.2 Hz, 1 H,
CHO), 3.36 [d, J = 13.2 Hz, 2 H, (NCHaHbPh)2], 3.17 (qd, J = 3.2,
6.9 Hz, 1 H, CHN), 1.15 (d, J = 6.9 Hz, 3 H, CH3CH).
13C NMR (100 MHz, CDCl3): d = 172.4, 159.4, 134.2, 130.1, 129.8,
129.5, 129.0, 128.6, 113.7, 78.6, 72.7, 55.2, 54.9, 54.6, 8.5.
ESI-MS: m/z = 420.2 [M + H]+.
HRMS (ESI): m/z [M + H]+ calcd for C26H30NO4: 420.2175; found:
(7) Takano, S.; Akiyama, M.; Sato, S.; Ogasawara, K. Chem.
Lett. 1983, 1593.
420.2169.
(8) For other methods for the cleavage of benzylidene and
methoxybenzylidene acetals of 1,2-glycols, see: (a) Greene,
T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis; Wiley: New York, 1999. (b) Kumar, P. S.;
Banerjee, A.; Baskaran, S. Angew. Chem. Int. Ed. 2010, 49,
804; and references cited therein.
(2S,3S)-1-Benzyl-2-{[(4-methoxybenzyl)oxy]methyl}-3-methyl-
aziridine (3a)
DIAD (95%, 0.035 mL, 0.170 mmol) was added to a soln of Ph3P
(48 mg, 0.183 mmol) in THF at 0 °C. The mixture was stirred for 25
min at 0 °C, then alcohol 5 (48 mg, 0.152 mmol) was added. The
soln was allowed to warm to r.t., stirred overnight, and then the sol-
vent was evaporated under reduced pressure. The crude residue was
purified by column chromatography on silica gel (cyclohexane–
EtOAc, 8:1) to give the aziridine 3a.
(9) For examples concerning applications for the synthesis of
complex natural products, see: (a) Solladié, G.; Lohse, O.
J. Org. Chem. 1993, 58, 4555. (b) Nakatsuka, M.; Ragan, J.
A.; Sammakia, T.; Smith, D. B.; Uehling, D. E.; Schreiber,
S. L. J. Am. Chem. Soc. 1990, 112, 5583. (c) Smith, A. B.
III; Hale, K. J.; Laakso, L. M.; Chen, K.; Riera, A.
Tetrahedron Lett. 1989, 30, 6963. (d) DiFranco, E.;
Ravikumar, V. T.; Salomon, R. G. Tetrahedron Lett. 1993,
34, 3247. (e) Barloy-Da Silva, C.; Pale, P. Tetrahedron:
Asymmetry 1998, 9, 3951. (f) Evans, D. A.; Kim, A. S.;
Metternich, R.; Novack, V. J. J. Am. Chem. Soc. 1998, 120,
5921. (g) Mulzer, J.; Mantoulidis, A.; Ohler, E. J. Org.
Chem. 2000, 65, 7456. (h) Munakata, R.; Katakai, H.; Ueki,
T.; Kurosaka, J.; Takao, K.-i.; Tadano, K.-I. J. Am. Chem.
Soc. 2004, 126, 11254.
(10) For examples concerning cleavage at the less hindered side
of ketals, see: (a) Eun, L.; Cheol, M. P.; Yun, J. S. J. Am.
Chem. Soc. 1995, 117, 8017. (b) Sato, I.; Akahori, Y.; Iida,
K.; Hirama, M. Tetrahedron Lett. 1996, 37, 5135.
(c) Hernández-Torres, J. M.; Liew, S.-T.; Achkar, J.; Wei, A.
Synthesis 2002, 487. (d) Balakumar, V.; Aravind, A.;
Baskaran, S. Synlett 2004, 647. (e) Joncke, S.; Liu, K.;
Schmidt, R. R. Chem. Eur. J. 2006, 12, 1274.
(11) (a) Pastó, M.; Moyano, A.; Pericàs, M. A.; Riera, A.
Tetrahedron: Asymmetry 1995, 6, 2329. For other examples
concerning cleavage at the more hindered position, see:
(b) Debenham, S. D.; Toone, E. J. Tetrahedron: Asymmetry
2000, 11, 385. (c) Zheng, B. Z.; Yamauchi, M.; Dei, H.;
Kusaka, S.; Matsui, K.; Yonemitsu, O. Tetrahedron Lett.
2000, 41, 6441. (d) Galal, A. E.; Tong, A.; Geert-Jan, B.
Tetrahedron Lett. 2002, 43, 4691. (e) Aravind, A.;
Baskaran, S. Tetrahedron Lett. 2005, 46, 743. (f)Shino,M.;
Kazuyuki, I.; Yukishige, I. J. Org. Chem. 2007, 72, 6107.
(12) For partial controlled direct cleavage of methoxybenzyl-
idene acetals of 1,3-diols, see: (a) Tsuri, T.; Kamata, S.
Tetrahedron Lett. 1985, 26, 5195. (b) Zhang, Z.;
Yield: 35 mg (77%); colorless oil; Rf = 0.24 (cyclohexane–EtOAc,
5:1); [a]D25 –21.4 (c 0.70, CHCl3).
1H NMR (400 MHz, CDCl3): d = 7.35–7.23 (m, 7 H, CHarom), 6.86
(d, J = 8.7 Hz, 2 H, CHarom), 4.47 (d, J = 11.5 Hz, 1 H, CHaHbAr),
4.39 (d, J = 11.5 Hz, 1 H, CHaHbAr), 3.80 (s, 3 H, OCH3), 3.60–
3.55 (m, 2 H, CHaHbO and CHaHbPh), 3.49–3.45 (m, 2 H, CHaHbO
and CHaHbPh), 1.80 (q, J = 5.8 Hz, 1 H, CH2CHN), 1.68 (quin,
J = 5.8 Hz, 1 H, CH3CHN), 1.17 (d, J = 5.8 Hz, 3 H, CH3CH).
13C NMR (100 MHz, CDCl3): d = 159.4, 139.5, 130.6, 129.5, 128.5,
128.0, 127.0, 113.9, 72.8, 68.9, 64.5, 55.4, 42.7, 38.6, 13.6.
ESI-MS: m/z = 298.1 [M + H].+
HRMS (ESI): m/z [M + H]+ calcd for C19H24NO2: 298.1807; found:
298.1796.
Supporting Information for this article is available online at
Acknowledgment
Thanks are expressed to Mr. Pierre Sánchez for his help in obtaining
mass spectrometric data and to Aurélien Lebrun for recording some
of the NMR spectra. We thank the MENRT for providing P.-Y. G.
with a research grant for his Ph.D. thesis project.
References
(1) (a) Juaristi, E. In Enantioselective Synthesis of b-Amino
Acids; Wiley-VCH: New York, 1997. (b) Juhl, K.;
Jorgensen, K. A. J. Am. Chem. Soc. 2002, 124, 2420.
(c) Aoyagi, Y.; Jain, R. P.; Williams, R. M. J. Am. Chem.
Soc. 2001, 123, 3472; and references cited therein.
Magnusson, G. J. Org. Chem. 1996, 61, 2394. For a
complete controlled direct cleavage of methoxybenzylidene
acetals of 1,3-diols, see: (c) Hernández-Torres, J. M.;
© Thieme Stuttgart · New York
Synthesis 2012, 44, 1247–1252