COMMUNICATIONS
Experimental Section
Differential Cleavage of Arylmethyl Ethers:
Reactivity of 2,6-Dimethoxybenzyl Ethers**
The ligand (c-C6H11)8Si8O11(OH)2 was prepared according to a procedure
previously described by Feher et al.[3] A solution of (c-C6H11)8Si8O11(OH)2
(2.52g, 2.3 mmol) in diethyl ether (60 cm3) was added to [Ce{N(SiMe3)2}3][9]
(0.713 g, 1.15 mmol) at ca. 208C. The mixture was stirred for 3 h. Pyridine
(2.1 g, 23 mmol) was added, and the mixture was stirred for 24 h. The
mixture was then filtered, and the filtrate was concentrated to ca. 20 cm3 in
J. R. Falck,* D. K. Barma, Rachid Baati, and
Charles Mioskowski
Protecting groups (PGs) serve a fundamental, albeit often
under-appreciated, role in synthesis.[1] The interplay of their
physico-chemical properties, availability, economics, and,
most importantly, their selective manipulation significantly
influences their ultimate utility. Consequently, milder or more
selective methodology applicable to the existing repertoire of
PGs and the development of new PGs with different
reactivities have the potential to expedite progress along a
broad front. Herein, we describe a convenient, high-yield
protocol for the selective cleavage of arylmethyl ethers with
stoichiometric chromium(ii) chloride/lithium iodide in mois-
ture-containing EtOAc [Eq. (1)].[2] We also highlight the 2,6-
dimethoxybenzyl moiety[3] as a versatile and cost-effective[4]
PG that extends the range of options for the selective removal
of arylmethyl ethers.
vacuo. Pale yellow crystals of
1 were gradually deposited. Further
concentration of the remaining mother liquor (ca. 10 cm3) in vacuo and
cooling to 228C afforded an additional crop of crystals of 1 (total yield:
1.97 g, 67%). Analysis calcd for C114H191CeN3O26Si16: C 53.4, H 7.45, N 1.6;
found: C 52.9, H 7.36, N 1.4; 1H NMR (400 MHz, [D6]benzene, 228C): d
8.86 (m, 6H; py), 7.0 (m, 3H; py), 6.8 (m, 6H; py), 2.12 ± 1.27 (brm, 160H;
CH2 in c-C6H11), 1.04 (m, 16H; CH in c-C6H11); 13C NMR (125 MHz,
[D6]benzene, 228C): d 150.45, 136.28, 123.76 (py), 28.77, 28.36, 28.12,
27.92, 27.62, 27.46 (CH2), 25.96, 25.16, 24.04 (CH); 29Si NMR (99 MHz,
[D6]benzene, 228C): d 60.68, 63.81, 69.59 (2:4:2); IR (KBr): nÄ
1
2923, 2850, 1599, 1448, 1108, 1067, 949, 847, 823, 750, 700, 622, 518, 403 cm
.
Alternatively, complex
1 was prepared by heating anhydrous CeCl3
(0.152 g, 0.615 mmol) for 24 h in THF under reflux and subsequent
treatment with (c-C6H11)8Si8O11(OH)2 (1.35 g, 1.23 mmol) in THF/pyridine
(75 cm3, 4/1). Crystallization from a concentrated solution in pyridine gave
crystals of 1 (yield: 0.87g, 55%).
Received: November 13, 2000 [Z16103]
[1] a) F. J. Feher, D. A. Newman, J. F. Walzer, J. Am. Chem. Soc. 1989, 111,
1741 ± 1748; b) F. T. Edelmann, Angew. Chem. 1992, 104, 600 ± 601;
Angew. Chem. Int. Ed. Engl. 1992, 31, 586 ± 587.
The scope of the de-O-benzylation by CrCl2/LiI[5] was
evaluated with a panel of representative arylmethyl ethers
(Table 1). Unsubstituted benzyl ethers were smoothly cleaved
at 758C in moisture-containing[6] EtOAc to give, after
aqueous isolation, the corresponding alcohol and benzyl
iodide (e.g., the conversion of 1 into 2 (Table 1, entry 1)) in
good to excellent yields. There was little or no reaction when
we used CrCl2 or LiI alone,[7] CrCl2/LiBr, or CrCl2/n-Bu4NI.[8]
On the other hand, CrI2 was just as effective as CrCl2/LiI, but
its expense precluded further exploration. Yields were much
lower in N,N-dimethylformamide, 1,2-dimethoxyethane, and
acetonitrile; the use of THF was limited by its reaction with
the reagent.
[2] For reviews, see a) F. J. Feher, T. A. Budzichowski, Polyhedron 1995,
14, 3239 ± 3253; b) P. G. Harrison, J. Organomet. Chem. 1997, 542, 141 ±
183; c) H. C. L. Abbenhuis, Chem. Eur. J. 2000, 6, 25 ± 32; d) V. Lorenz,
A. Fischer, S. Gieûmann, J. W. Gilje, Y. Gunꢁko, K. Jacob, F. T.
Edelmann, Coord. Chem. Rev. 2000, 206 ± 207, 321 ± 368.
[3] a) F. J. Feher, D. Soulivong, A. G. Eklund, Chem. Commun. 1998, 399 ±
400; b) F. J. Feher, D. Soulivong, A. G. Nguyen, Chem. Commun. 1998,
1279 ± 1280; c) F. J. Feher, R. Terroba, J. W. Ziller, Chem. Commun.
1999, 2309 ± 2310.
[4] Crystal data: for 1: C111H195CeN3O28Si16, Mr 1304.63, monoclinic,
space group C2/c, a 20.474(5), b 21.244(5), c 32.843(10) , b
102.95(3)8, V 13922(6) 3, Z 4, 1calcd 1.245 gcm 3, F(000) 5552,
T 153(2) K, m(MoKa) 0.529 mm 1, 3.60 < q < 22.548; of 13986 re-
flections 9079 were independent (Rint 0.0356); the final R indices
were R1 0.0511 and wR2 0.1358 (I > 2s(I)), and R1 0.0596, wR2
0.1471 (all data); GOF on F 2: 1.094; max./min. residual electron density
1.211/ 0.447 e 3. Data were collected on a Siemens-Stoe AED2
diffractometer. The structure was solved by direct methods
(SHELXTS-90) and refined by full-matrix least-squares methods on
F 2. All non-hydrogen atoms were refined anisotropically, and the
hydrogen atoms were included by using a riding model. Crystallo-
graphic data (excluding structure factors) for the structure reported in
this paper have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication no. CCDC-150263. Copies
of the data can be obtained free of charge on application to CCDC, 12
Union Road, Cambridge CB21EZ, UK (fax: (44)1223-336-033;
e-mail: deposit@ccdc.cam.ac.uk).
p-Phenylbenzyl ether[9] 3 likewise gave rise to 2 (Table 1,
entry 2) in excellent yield under similar conditions as 1.
Notably, glycerol derivative 4 furnished secondary alcohol 5
(Table 1, entry 3) as the sole product. Such regioselectivity is
reminiscent[10] of other transition metal promoted de-O-
[*] Prof. J. R. Falck, Dr. D. K. Barma
Department of Biochemistry, University of Texas
Southwestern Medical Center, Dallas, TX 75390-9038 (USA)
Fax : (1)214-648-6455
[5] P. S. Gradeff, K. Yunlu, T. J. Deming, J. M. Olofson, R. J. Doedens, W. J.
Evans, Inorg. Chem. 1990, 29, 420-424.
[6] W. J. Evans, T. J. Deming, J. M. Olofson, J. W. Ziller, Inorg. Chem. 1989,
28, 4027 ± 4034.
[7] J. B. Jones, Acta Crystallogr. Sect. B 1968, 24, 355 ± 358.
[8] a) F. T. Edelmann, Y. Gunꢁko, S. Gieûmann, F. Olbrich, Inorg. Chem.
1999, 38, 210 ± 211; b) R. Duchateau, R. J. Harmsen, H. C. L. Abben-
huis, R. A. van Santen, A. Meetsma, S. K.-H. Thiele, M. Kranenburg,
Chem. Eur. J. 1999, 5, 3130 ± 3135.
Dr. R. Baati, Dr. C. Mioskowski
Â
Universite Louis Pasteur de Strasbourg
Â
Faculte de Pharmacie
Á
Laboratoire de Synthese Bio-Organique (UMR 7514)
67401 Illkirch (France)
[**] Financial support was provided by the Robert A. Welch Foundation,
NIH (GM31278, DK38226), CNRS, Instituts de Recherche Pierre
Fabre (to R.B.), and an unrestricted grant from Taisho Pharmaceutical
Co., Ltd. We thank Dr. Naoya Ono for helpful discussions.
[9] D. C. Bradley, J. S. Gothra, F. A. Hart, J. Chem. Soc. Dalton Trans. 1973,
1021 ± 1023.
Supporting information for this article is available on the WWW under
Angew. Chem. Int. Ed. 2001, 40, No. 7
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