Ferrocenyl ethers

The ferrocene nucleus proved to be absolutely unable to undergo the rearrangements characteristic of the benzene ring, so the Claisen rearrangement of allyl ferrocenyl ether 291), the benzidine rearrangement of hydrazo-ferrocene 294-296), and the Sommelet rearrangement in the ferrocene series were all unsuccessful. 

Scheme 5-32 shows a series of ferrocenyl compounds that can be formally considered as derivatives of the ferrocenyl chalcogenols, Fc-EH (E = O, S, Se, Te), including ferrocenyl ethers, thioethers, selenoethers and telluroethers. The analogous l,T-ferrocenediyl compounds, formally derived from fc(EH)2 (E = O, S, Se, Te), are presented in Scheme 5-33 (see Appendix). 

Benzophenone-photosensitized hydrolysis of CpFe(Cp—CR1=NR8) leads to the corresponding ketone or aldehyde CpFe(Cp—COR1).242 Photodecomposition of ferrocenyl ethers,243 and photochemical oxidation of ferrocene carboxylic acids on 254 nm irradiation have been discussed.244... 

The solid is separated by filtration and the filtrate is extracted with three 150-ml. portions of ether. Caution Gloves should be worn when handling this solution because of the large amount of cyanide it contains.) The solid is dissolved in ether and this solution is combined with the extracts. The combined ethereal solutions are washed with water and dried over 5 g. of sodium sulfate. Removal of the solvent by distillation leaves crude ferrocenyl-acetonitrile as a solid or as an oil that crystalli/.es on being scratched. I he nitrile is dissolved in about 200 ml. of boiling... 

To a mixture of vinyl bromide (40 mmol) and the catalyst dichloro-[(R)-Af,N-dimethyl-l-[(.S)-2-(diphenylphosphino)ferrocenyl]ethylamine]-palladium(n) (0.2 mmol) was added an ethereal solution of [a-(trimethyl-silyl)benzyl]magnesium bromide (0.6-1 m, 80 mmol) at —78 °C. The mixture was stirred at 30 °C for 4 days, and then cooled to 0 °C and hydrolysed with dilute aqueous HC1 (3 m). The organic layer was separated, and the aqueous layer was re-extracted with ether. The combined organic extracts were washed with saturated sodium hydrogen carbonate solution and water, and dried. Concentration and distillation gave the chiral allylsilane (79%, 66% ee), b.p. 55°C/0.4mmHg. 

While the ambiguity of the catalysis of the Diels-Alder reaction needs to be carefully elucidated, the application of the ferrocenyl carbocations in the Mukaiyama aldolization turned out evidently to be unrealisable due to their interaction with the TMS enol ether that produces TMSOTf, which proved readily to catalyze the aldolization [154]. 

Tetrahydrobis(benzofuran) is produced by a tandem cyclization reaction from the bis-vinyl ether on reaction with catalytic quantities of rhodium(l) salts in the presence of electron-rich phosphine ligands <20030L1301>. Thus, employing 10mol% of [RhCl(coe)2]2 with 20mol% of a dicyclohexyl ferrocenyl phosphine ligand produces the bis-cyclized product (coe = cyclooctene Equation 67). 

An extensive spectroscopic and mechanistic study on the enantioselective Cu/ferrocenyl bisphosphine-catalyzed conjugate addition has been performed. Several parameters such as solvent, nature of the halide present in the Grignard reagent and Cu(I) source, and additives (i.e. dioxane and crown ethers) were identified. These factors directly affect the formation and nature of the intermediate active species, and therefore the selectivity, rate and overall outcome of the reaction. Importantly, the presence of and Br ions in the reaction are essential in order to achieve high selectivity and efficiency. 

Additional studies showed that iodoferrocene was approximately as reactive as l-iodo-2-nitrobenzene under Ullmann conditions. A mixed Ullmann reaction involving these two reactive aryl halides produced 2-nitrophenylferrocene. Ullmann condensations of iodoferrocene with various sodium phenoxides and sodium arenethiolates likewise led to ferrocenyl aryl ethers and sulfides, respectively (84, 85). 

A number of observations have been made which qualitatively suggest that carbonium ions adjacent to metallocene systems possess unusual stability. Ferro-cenecarboxaldehyde, for example, is soluble in dilute hydrochloric acid (5), ferrocenyl carbinols such as ferrocenyl phenyl carbinol form ethers with great ease (124), and ferrocenylmethylcarbinol can be dehydrated to vinylferrocene under exceedingly mild conditions (114). The concept of stabilizations of this type has also been used to explain certain anomalous ring substitution reactions. 

Addition of water (36) or alcohols (37—39) direcdy to butadiene at 40—100°C produces the corresponding unsaturated alcohols or ethers. Acidic ion exchangers have been used to catalyze these reactions. The yields for these latter reactions are generally very low because of unfavorable thermodynamics. At 50°C addition of acetic acid to butadiene produces the expected butenyl acetate with 60—100% selectivity at butadiene conversions of 50%. The catalysts are ion-exchange resins modified with quaternary ammonium, quaternary phosphonium, and ammonium substituted ferrocenyl ions (40). Addition of amines yields unsaturated alkyl amines. The reaction can be catalyzed by homogeneous catalysts such as Rh[P(C(5H5)3]3Q (41) or heterogeneous catalysts such as MgO and other solid bases (42). 

Synthetic peptides containing side-chain modification have also been used as molecular scaffolds for the preparation of multiple receptors and molecular devices. 5 These include the use of crown ethers, cyclodextrins, porphyrins, and peptides with metal-binding sites (including ferrocenyl and EDTA side chains) (Section 9.4). Cyclization procedures have been developed to prepare biologically active cycloisodityrosine peptides which contain 14-or 17-membered rings (Section 9.5). The use of tryptathionine, a cross-linking dipeptide consisting of side-chain-to-side-chain linked L-Trp-L-Cys that is present in phallotoxins, 6 a family of cyclic heptapeptides, is also described (Section 9.6). 

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