Dichlorobis(cyclopentadienyl)hafnium-Silver(I) Salts1


[12116-66-4]  · C10H10Cl2Hf  · Dichlorobis(cyclopentadienyl)hafnium-Silver(I) Salts  · (MW 379.59) (AgClO4)

[7783-93-9]  · AgClO4  · Dichlorobis(cyclopentadienyl)hafnium-Silver(I) Salts  · (MW 207.32) (AgOSO2CF3; AgOTf)

[2923-28-6]  · CAgF3O3S  · Dichlorobis(cyclopentadienyl)hafnium-Silver(I) Salts  · (MW 256.93) (AgBF4)

[14104-20-2]  · AgBF4  · Dichlorobis(cyclopentadienyl)hafnium-Silver(I) Salts  · (MW 194.68) (AgPF6)

[26042-63-7]  · AgF6P  · Dichlorobis(cyclopentadienyl)hafnium-Silver(I) Salts  · (MW 252.83)

(can activate glycosyl fluorides for O-glycosidation;2 can convert aryl O-glycosides to the corresponding aryl C-glycosides3)

Physical Data: see entries for Dichlorobis(cyclopentadienyl)hafnium and individual silver salts.

Handling, Storage, and Precautions: the reagents are combined just before use by adding the Ag salt to a solution of Cp2HfCl2. AgClO4 leads to the best reactivity, but has a potential hazard of explosion.4 AgOTf is recommended as a safe alternative with slightly decreased reactivity. Other silver salts (e.g. AgBF4, AgPF6, AgAsF6) are less effective, but sometimes offer unique stereochemical preferences.2,3 Molecular sieves 4Å are often used for removal of water in small scale runs, but are not necessarily essential.

Glycosyl fluorides are widely used in glycoside synthesis, because of their stability, ease of handling and availability of specific activation methods.5 Although Tin(II) Chloride-AgClO45a is most often utilized, the extremely high reactivity offered by Cp2HfCl2-AgClO42 renders it the promoter of choice for the glycosidation of sterically demanding substrates. Intermediate cationic hafnocene complexes are believed to be the origin of the high reactivity, which led to the finding that the use of the combination in 1:2 ratio leads to an even more increased reactivity (eq 1).2d The efficiency of this new protocol is clearly demonstrated in the synthesis of oligo- or even polysaccharides.6e

A number of useful applications are reported for the synthesis of various classes of glycoconjugates ranging from macrolides, e.g. (1),2a,b,c to oligosaccharide structures embedded in glycolipids.6 One of the highlights in the latter context is the block synthesis of sialyl LeX related oligosaccharides via the coupling of the glycosyl fluoride (2).6a,b Applicability to glycosidation of amino sugars is another notable feature of this activation method.2b,c,6

A Lewis acid-mediated synthetic reaction of aryl C-glycosides is reported, which involves (1) the initial formation of aryl O-glycosides at low temperature, and (2) its in situ rearrangement to the corresponding aryl C-glycosides (eq 2).3 A particularly useful feature is that the C-C bond is formed regioselectively at the position ortho to the phenol.

Both processes can be promoted by general Lewis acids, but Cp2HfCl2-AgClO4 is prominent in terms of the reactivity and stereoselectivity. These features are well illustrated by their application in the total syntheses of vineomycinone B2 methyl ester (4)7 and gilvocarcin M (5).8 Donor solvents, such as Et2O or MeCN, retard the second step, thereby providing a useful synthetic method for aryl O-glycosides.3b

Cp2HfCl2-AgClO4 is useful in nucleoside synthesis via the coupling of glycosyl fluorides and bis(trimethylsilyl)uracil (eq 3).9

Related Reagents.

Dichlorobis(cyclopentadienyl)hafnium; Dichlorobis(cyclopentadienyl)zirconium-Silver(I) Salts.

1. Suzuki, K.; Matsumoto, T. J. Synth. Org. Chem. Jpn. 1993, 51, 718.
2. (a) Matsumoto, T.; Maeta, H.; Suzuki, K.; Tsuchihashi, G. TL 1988, 29, 3567. (b) Suzuki, K.; Maeta, H.; Matsumoto, T.; Tsuchihashi, G. TL 1988, 29, 3571. (c) Matsumoto, T.; Maeta, H.; Suzuki, K.; Tsuchihashi, G. TL 1988, 29, 3575. (d) Suzuki, K.; Maeta, H.; Matsumoto, T. TL 1989, 30, 4853.
3. (a) Matsumoto, T.; Katsuki, M.; Suzuki, K. TL 1988, 29, 6935. (b) Matsumoto, T.; Katsuki, M.; Suzuki, K. CL 1989, 437. (c) Matsumoto, T.; Hosoya, T.; Suzuki, K. TL 1990, 31, 4629. (d) Matsumoto, T.; Hosoya, T.; Suzuki, K. SL 1991, 709.
4. Brinkley Jr., S. R. JACS 1940, 62, 3524.
5. (a) Mukaiyama, T.; Murai, Y.; Shoda, S. CL 1981, 431 (SnCl2-AgClO4). (b) Hashimoto, S.; Hayashi, M.; Noyori, R. TL 1984, 25, 1379 (TMSOTf and SiF4). (c) Nicolaou, K. C.; Chucholowski, A.; Dolle, R. E.; Randall, J. L. CC 1984, 1155 (BF3.OEt2). (d) Kunz, H.; Sager, W. HCA 1985, 68, 283 (BF3.OEt2). (e) Kreuzer, M.; Thiem, J. Carbohydr. Res. 1986, 149, 347 (TiF4). (f) Kobayashi, S.; Koide, K.; Ohno, M. TL 1990, 31, 2435 (Me2GaX). (g) Wessel, H. P. TL 1990, 31, 6863 (Tf2O). (h) Maeta, H.; Matsumoto, T.; Suzuki, K. Carbohydr. Res. 1993, 249, 49 (Bu2SnCl2-2AgClO4).
6. (a) Nicolaou, K. C.; Caulfield, T. J.; Kataoka, H.; Stylianides, N. A. JACS 1990, 112, 3693. (b) Nicolaou, K. C.; Hummel, C. W.; Iwabuchi, Y. JACS 1992, 114, 3126. (c) Matsuzaki, Y.; Ito, Y.; Ogawa, T. TL 1992, 33, 6343. (d) Nicolaou, K. C.; Bockovich, N. J.; Carcanague, D. R.; Hummel, C. W.; Even, L. F. JACS 1992, 114, 8701. (e) Matsuzaki, Y.; Ito, Y.; Nakahara, Y.; Ogawa, T. TL 1993, 34, 1061.
7. (a) Matsumoto, T.; Katsuki, M.; Jona, H.; Suzuki, K. TL 1989, 30, 6185. (b) Matsumoto, T.; Katsuki, M.; Jona, H.; Suzuki, K. JACS 1991, 113, 6982.
8. Matsumoto, T.; Hosoya, T.; Suzuki, K. JACS 1992, 114, 3568.
9. Matheu, M. I.; Echarri, R.; Castillón, S. TL 1992, 33, 1093.

Keisuke Suzuki & Takashi Matsumoto

Keio University, Yokohama, Japan

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