SYNTHESIS OF ENANTIOMERICALLY PURE FERROCENES FROM GLYCOFURANOSYL-CYCLOPENTADIENES, SYNTHETIC EQUIVALENTS OF (ALKOXYALKYL)FULVENES

Cyclopentadienyl C-glycosides (= glycosyl-cyclopentadienes) have been prepared as latent fulvenes. Their reaction with nucleophiles leads to cyclopentadienes substituted with (protected) alditol moieties and, h ence, to enantiomerically pure metallocenes. Treatment of 1 with cyclo pentadienyl anion gave the epimeric glycosyl-cyclopentadienes 6/7 (Sch eme 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-Ald er addition of N-phenylmaleimide to 6a/b ca. 3:7 at room temperature y ielded 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 isola tion or in situ) with LiAlH4 gave the cyclopentadienylmannitols 12a/b (80%) which were converted to the silyl ethers 13a/b (Scheme 2). Lithi ation of 13a/b and reaction with FeCl2 or TiCl4 led to the symmetric f errocene 14 (76%) and the titanocene 15 (34%), respectively. The mixed ferrocene 16 (63%) was prepared from 13a/b and pentamethylcyclopentad iene. Treatment of 6/7 with PhLi at -78 degrees 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 wi th FeCl2 afforded the symmetric ferrocenes 21 and 22 and the mixed fer rocene 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 conforma tional analysis. The reaction of the ribofuranose 24 with cyclopentadi enylsodium led to the epimeric C-glycosides 27a/b and 28a/b (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 f errocene 26 (79%) using the standard method. Phenylation of 27/28, des ilylation, and isopropylidenation gave a 20:1 mixture of 33a/b and 34a /b (86%) which was separated by prep. HPLC. The same mixture was obtai ned upon phenylation of the fulvene 32 which was obtained in 36% yield from the reaction of the aldehydo-ribose 30 with cyclopentadienylsodi um at-100 degrees. Lithiation of 33/34 and reaction with FeCl2 gave th e symmetric ferrocene 35 (88%). Similarly, the aldehydo-arabinose 36 w as transformed via the fulvene 37 (32%) into a 18:1 mixture of 38a/b a nd 39a/b (78%) and, hence, into the ferrocene 40 (83%). Conformational analysis allowed to assign the configuration of 33-35, whereas an X-r ay 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 re duction yielded (+)-(S)-43 and (-)-(R)-43, respectively.