Planar Chiral Ferrocene Derivatives

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). 

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]. 

So far, the most relevant method for the preparation of enantiopure (or enantiomerically enriched) planar-chiral ferrocene derivatives relies upon a diastereoselective orrAo-lithia-tion and subsequent reaction with an appropriate electrophile. Still the most prominent example of this methodology is due to the pioneering work of Ugi and co-workers (Scheme 1) [3]. 

In 2007, Xia and You realized the synthesis of planar chiral ferrocene derivatives by utilizing the chiral oxazoline auxiliary strategy. As shown in Scheme 5.3, the planar chiral ferrocene derivative (S,Pp)-5 was obtained as a single... 

Soon after, Cui, Wu, and co-workers reported a highly efficient oxidative Heck reaction for the synthesis of planar chiral ferrocene derivatives (Scheme 5.10). By employing a similar catalytic system, all kinds of 2-alkenylated ferrocene derivatives were easily accessed via Pd/MPAA catalyzed asymmetric C—H bond functionalization. It was suggested that the Pd° species was oxidized to Pd at the end of the catalytic cycle by Ai,Ai-dime-thylaminomethylferrocenium which is generated from Ai,Ai-dimethylamino-methyl-ferrocene oxidized by air. 

The generation of planar chirality via an enantioselective C(sp )—H bond functionalization is another promising dimension of asymmetric C—H bond functionalization. Some recent results in the field of Pd-catalyzed synthesis of planar chiral ferrocene derivatives via C(sp )—H bond functionalization... 

Investigation of the production of planar chiral ferrocene derivatives of use in catalytic asymmetric chemistry has led to the lithiation of N,AI-dimethylferrocenylmethylamine in the presence of non-stoichiometric levels of the chiral diamine tmcda (20% wrt ferrocenyl ligand). Data suggest the ability of this ligand to promote catalytic stereoselective ortho lithiation through the facile ability of Et20 to replace the chiral auxiliary as the lithiate converts from tmcda-complexed monomer to Et20-complexed dimer with retention of stereochemistry. ... 

In 1998, Ruble and Fu [10] reported on the use of ferrocene-derived chiral 4-aminopyridines [11] in the Steglich rearrangement of 2-aryl-4-alkyloxazolones (Scheme 40.3). After the systematic optimization of several reaction parameters, the authors found that the planar-chiral ferrocene derivative (S)-l catalyzed the rearrangement of an array of 0-benzyloxycarbonyl azlactones with total... 

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