Synthesis of Enantiomerically Pure Ferrocenes from Glycofuranosyl‐cyclopentadienes, synthetic equivalents of (alkoxyalkyl)fulvenes

Abstract

Cyclopentadienyl C-glycosides ( = glycosyl-cyclopentadienes) have been prepared as latent fulvenes. Their reaction with nucleophiles leads to cyclopentadienes substituted with (protected) alditol moieties and, hence, to enantiomerically pure metallocenes. Treatment of 1 with cyclopentadienyl anion gave the epimeric glycosyl-cyclopentadienes 6/7 (Scheme 1). Each epimer consisted of a ca. 1:l mixture of the 1,3-and 1,4-cyclopentadienes a and b, respectively, which were separated by prep. HPLC. Slow regioisomerisation occurred at room temperature. Diels-Alder addition of N-phenylmaleimide to 6a/b cu. 3 :7 at room temperature yielded three 'endo'-adducts, i.e., a disubstituted alkene (8 or 9,25%) and the trisubstituted alkenes 10 (45%) and 11 (13 %). The structure of 10 was established by X-ray analysis. Reduction of 6/7 (after isolation or in situ) with LiA1H4 gave the cyclopentadienylmannitols 12a/b (80%) which were converted to the silyl ethers 13a/b (Scheme 2). Lithiation of 13a/b and reaction with FeC1, or TiCI, led to the symmetric ferrocene 14 (76%) and the titanocene 15 (34%), respectively. The mixed ferrocene 16 (63 %) was prepared from 13a/b and pentamethylcyclopentadiene. Treatment of 6/7 with PhLi at -78" was assigned on the basis of a conformational analysis. The reaction of the ribofuranose 24 with cyclopentadienylsodium led to the epimeric C-glycosides 27a/b and 28a/b (57%, ca. 1 :I, Scheme 3 ) . The in-situ reduction of 27/28 with LiAIH, followed by isopropylidenation gave 25a/b (65%) which were transformed into the ferrocene 26 (79 %) using the standard method. Phenylation of 27/28, desilylation, and isopropylidenation gave a 20: 1 mixture of 33a/b and 34a/b (86%) which was separated by prep. HPLC. The same mixture was obtained upon phenylation of the fulvene 32 which was obtained in 36% yield from the reaction of the aldehyde-ribose 30 with cyclopentadienylsodium at -100". Lithiation of 33/34 and reaction with FeCI, gave the symmetric ferrocene 35 (88%). Similarly, the aldehyde-arabinose 36 was transformed via the fulvene 37 (32%) into a 18 :1 mixture of 38a/b and 39a/b (78 YO) and, hence, into the ferrocene 40 (83 %). Conformational analysis allowed to assign the configuration of 3S35, whereas an X-ray analysis of 40 established the (lS)-configuration of 38a/b and 40. The opposite configuration at C(1) of 38a/b and 33a/b was established by chemical degradation (Scheme 4 ) . Hydrogenation (+ 41 and 44, resp.), deprotection (+ 42 and 45, resp.), NaIO, oxidation, and NaBH, reduction yielded ( Monocyclopentadienyl titanium [ 191, zirconium [20], and hafnium [20] complexes possessing carbohydrate-derived alkoxy ligands have been used in stoichiometric amounts for the highly enantioselective addition of alkyl [20] [21] and ally1 groups [20-231 and of ester enolates [20-221 [24] to aldehydes. Zirconocenes have been used for the ring

Titanocene Dihalides and Ferrocenes Bearing a Pendant α-d-Xylofuranos-5-yl or α-d-Ribofuranos-5-yl Moiety. Synthesis, Characterization, and Cytotoxic Activity

“…Several reviews dealing with carbohydrate–metal conjugates published in the last 14 years show an increasing interest in the field. − Whereas numerous ferrocene–carbohydrate conjugates have been described, − there are very few examples of carbohydrate-modified cyclopentadienyl ligands in titanocene dichlorides. Titanocene dichlorides (see Chart ) bearing cyclopentadienyl rings modified with d -mannitol ( I ), α- d -xylofuranose ( II ), and α- d -galactopyranose ( III ) , have been reported, although no cytotoxicity data were presented. A family of titanocene dichlorides bearing one ( IV and V ) or two ( VI and VII ) modified ribofuranose moieties was recently patented .…”