Chiral ferrocene derivatives

Palladacycles are defined as compounds with a Pd-C CT-bond with the Pd being stabilized by one or two neutral donor atoms, typically forming 5- or 6-membered rings [51]. Ferrocenyl palladacycles constitute a particularly attractive catalyst class partly due to the element of planar chirality. The first diastereoselective cyclopallada-tion of a chiral ferrocene derivative was reported in 1979 by Sokolov [52, 53]. 

Norbomene was functionalized with cyclodextrins and surface grafted onto silica-based supports using ROMP (44). The CSP are suitable for the enantioselective separation various amino acids, including jS-blockers and other compounds, such as chiral ferrocene derivates. 

Pioneering work by Pracejus et al. in the 1960s, using alkaloids as catalysts, afforded quite remarkable 76% ee in the addition of methanol to phenylmethyl-ketene [26-29]. In 1999 Fu et al. reported that of various planar-chiral ferrocene derivatives tried, the azaferrocene 35 performed best in the asymmetric addition of methanol to several prochiral ketenes [30, 31]. In the presence of 10 mol% catalyst 35 (and 12 mol% 2,6-di-tert-butylpyridinium triflate as proton-transfer agent), up to 80% ee was achieved (Scheme 13.16). 

Chung et al. reported the enantioselective synthesis of chiral NHCs, such as 6, using a chiral ferrocene derivative (Scheme 8) [28]. The nucleophilic substitution of the hydroxy function by an imidazole in an acidic medium gives the imidazolium salt with retention of the configuration at the chiral C-atom. 

There are a number of examples of chiral ferrocene derivatives prepared by reaction of substituted cyclopenta-diene anions with FeCl2 or a monocyclopentadienyl iron species rather than using the strategy of introduction and modification of a side chain on ferrocene itself. Addition... 

So far, all approaches to chiral ferrocenes have started with unsubstituted ferrocene and the chirality introduced later. If a chiral derivative of cyclopentadiene could be prepared, it would be possible to obtain a chiral ferrocene derivative by simple reaction with FeClj and base. This concept has been realized by several groups. 

Fig. 4-12. Chiral ferrocene derivatives from chiral cyclopentadienes.

Intact baker s yeast resolves 2-methyl-ferrocenealdehyde kinetically, leading to 88% ee in the remaining (I )-aldehyde and 77% ee in (S)-2-methyl-ferrocenemethanol (Fig. 4-21 c) [16], A comparatively high enantiomeric excess is observed quite often in baker s yeast reductions of suitably constructed planar chiral ferrocene derivatives [18]. 

Asymmetric induction in ring closure reactions of central chiral ferrocene derivatives has been reported. Moderate diastereoselectivity was found in the ring closure of the enantiomeric 4-ferrocenyl-2-methyl-2-phenyl-butanoic acids by treatment with trifluoroacetic anhydride (Fig. 4-211) [10]. The diastereoisomeric ketones could be separated by chromatography. A higher induction was observed in an asymmetric Pictet — Spengler type cyclization of a reactive imine formed from enantiomerically pure 2-ferrocenyl-2-propylamine and formaldehyde, as only one isomer of the product was detected (Fig. 4-21 g) [135, 136]. 

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