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Synthesis of Enantiomerically Pure Ferrocenes from Glycofuranosyl‐cyclopentadienes, synthetic equivalents of (alkoxyalkyl)fulvenes
Author(s) -
Vedø Per,
Chauvin Rémi,
Li Zhi,
Bernet Bruno,
Vasella Andrea
Publication year - 1994
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19940770620
Subject(s) - chemistry , cyclopentadienyl complex , ferrocene , silylation , metallocene , medicinal chemistry , fulvenes , organic chemistry , catalysis , polymer , electrode , electrochemistry , polymerization
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 LiAlH 4 gave the cyclopentadienylmannitols 12a / b (80%) which were converted to the silyl ethers 13a / b ( Scheme 2 ). Lithiation of 13a / b and reaction with FeCl 2 or TiCl 4 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 FeCl 2 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 LiAlH 4 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 FeCl 2 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 (1 S )‐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 4 oxidation, and NaBH 4 reduction yielded (+)‐( S )‐ 43 and (−)‐( R )‐ 43 , respectively.