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

Publisher Website
Google Scholar
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. 1:1 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 ca. 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 LiAlH4 gave the cyclopentadienylmannitols 12a/b (80%) which were converted to the silyl ethers 13a/b (Scheme 2). Lithiation of 13a/b and reaction with FeCl2 or TiCl4 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° gave a 5:3 mixture of the 1‐C‐phenylated alcohols 17a/b and 18a/b (71%) which were silylated to 19a/b and 20a/b, respectively. Lithiation of 19/20 and reaction with FeCl2 afforded the symmetric ferrocenes 21 and 22 and the mixed ferrocene 23 (54:15:31, 79%) which were partially separated by MPLC. The configuration at C(1) of 17–22 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 (57%, ca. 1:1, Scheme 3). The in‐situ reduction of 27/28 with LiAlH4 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 aldehydo‐ribose 30 with cyclopentadienylsodium at −100°. Lithiation of 33/34 and reaction with FeCl2 gave the symmetric ferrocene 35 (88%). Similarly, the aldehydo‐arabinose 36 was transformed via the fulvene 37 (32%) into a 18:1 mixture of 38a/b and 39a/b (78%) and, hence, into the ferrocene 40 (83%). Conformational analysis allowed to assign the configuration of 33–35, whereas an X‐ray analysis of 40 established the (1S)‐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.), NaIO4 oxidation, and NaBH4 reduction yielded (+)‐(S)‐43 and (−)‐(R)‐43, respectively.