Ferrocene derivatives planar chirality

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]. 

Fu has reported a planar-chiral bisphosphorus ligand 45 with a phosphaferrocene backbone. The ligand has provided enantioselectivity up to 96% ee in the hydrogenation of a-dehydroamino acid derivatives.99 Another planar-chiral ferrocene-based bisphosphorus ligand 46 has been reported by Kagan recently and enantioselectivity up to 95% ee has been obtained in the reduction of dimethyl itaconate.100... 

While Josiphos 41 also possessed an element of atom-centered chirality in the side chain, Reetz reported a new class of ferrocene-derived diphosphines which had planar chirality only ligands 42 and 43, which have C2- and C -symmetry, respectively.87 Rhodium(i)-complexes of ligands (—)-42 and (—)-43 were used in situ as catalysts (0.75 mol%) for the hydroboration of styrene with catecholborane 1 for 12 h in toluene at — 50 °C. The rhodium/ i-symmetric (—)-43 catalyst system was the more enantioselective of the two - ( -l-phenylethanol was afforded with 52% and 77% ee with diphosphines (—)-42 and (—)-43, respectively. In both cases, the regioselectivity was excellent (>99 1). With the same reaction time but using DME as solvent at lower temperature (—60 °C), the rhodium complex of 43 afforded the alcohol product with an optimum 84% ee. 

The synthesis of ferrocene 9 relied on chemistry introduced by Sammakia, Uemura, and Richards [18]. They had shown that 2-ferrocenyl oxazoline 10 derived from t-leucine could be selectively deprotonated and trapped with electrophiles to afford ortho-functionalized planar-chiral products 11 with excellent diastereoselectivities (Scheme 2.1.2.3). Following this strategy, 9 became accessible in a highly straightforward manner by trapping the lithiated intermediate derived from 10 with benzophenone [10, 11],... 

The same synthetic strategy as in the synthesis of planar-chiral ferrocenes was applied to the preparation of rheniumtricarbonyl 14, which has also been studied as a catalyst in aryl transfer reactions [21], Subsequently, this chemistry has been extended, and various catalytic applications of cyrhetrenes 15, 16 (AAPhos), and related derivatives have recently been demonstrated [22]. 

Quite efficient nucleophilic catalysts with planar (21a-c) and axial (22a-d) chirality were recently developed by Fu et al. [17-22] and Spivey et al. [23-25], The ferrocene-derived catalysts developed by Fu (21a-c) were first tested in the kinetic resolution of aryl alkyl carbinols with diketene as the acyl donor. 

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). 

N-Cumyl planar chiral ferrocenes, also prepared by DoM chemistry, lead to useful new ferrocenyl derivatives C. Metallinos, V. Snieckus, in preparation. 

We are already well accustomed with the historical relationship seen in the development of NHC ligands with special features. They often follow the example of successful phosphane ligands. Chiral NHC are no exception, although in key areas the very difference in shape between NHC and phosphanes prevents the development of NHC ligands as structural phosphane mimics. The axial (atropisomers with binaphthyl backbone [6,7]) and planar (ferrocene derivatives [8,9], [2,2]-paracyclophanes [10,11]) chiral examples, however, are styled on their phosphane predecessors [12-15]. We will first look at the unique options for NHC ligands before we turn to the more familiar phosphane mimics. 

Ferrocene reacts with acetyl chloride and aluminum chloride to afford the acylated product (287) (Scheme 84). The Friedel-Crafts acylation of (284) is about 3.3 x 10 times faster than that of benzene. Use of these conditions it is difficult to avoid the formation of a disubstituted product unless only a stoichiometric amount of AlCft is used. Thus, while the acyl substituent present in (287) is somewhat deactivating, the relative rate of acylation of (287) is still rapid (1.9 x 10 faster than benzene). Formation of the diacylated product may be avoided by use of acetic anhydride and BF3-Et20. Electrophilic substitution of (284) under Vilsmeyer formylation, Maimich aminomethylation, or acetoxymercuration conditions gives (288), (289), and (290/291), respectively, in good yields. Racemic amine (289) (also available in two steps from (287)) is readily resolved, providing the classic entry to enantiomerically pure ferrocene derivatives that possess central chirality and/or planar chirality. Friedel Crafts alkylation of (284) proceeds with the formation of a mixture of mono- and polyalkyl-substituted ferrocenes. The reaction of (284) with other... 

Many of the ferrocene ligand families described above are derived from a resolved chiral precursor (i.e. 289). Efforts to (76) prepare planar chiral ferrocenes also employ other strategies that rely on a directed metalation (see Orthometalation). Sulfoxide (338), acetal (339), and oxazolines of type (321)... 

Optically active ferrocene derivatives, particularly ferrocenyl phosphines, have hitherto been utilized as chiral ligands for a wide range of asymmetric synthesis. We have now revealed that the ferrocene moiety can easily be incorporated in amino alcohol ligands instead of phosphinic ligands. The preparative methods for several types of ferrocenylamino alcohols were developed and they were successfully used to catalyze enantioselective addition of dialkylzinc to aldehydes with high enantio-selectivity. In particular, 1,2-disubstituted ferrocenyl amino alcohols with planar... 

Ugi has coined the term stereorelating synthesis for the sequence lithiation/reac-tion with electrophiles [62,118], and used this technique as a method for the chemical correlation of the structure and for the determination of the enantiomeric purity of many 1,2-disubstituted ferrocene derivatives obtained either by resolution or by asymmetric synthesis (for a compilation, see [118]). It is important to note that all stereochemical features discussed above for central chiral compounds, such as retentive nucleophilic substitution, remain valid when more substituents are present at the ferrocene ring and the conversion of functional groups in planar chiral ferrocenes can be achieved by the same methods as described. 

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]. 

Planar chiral compounds should also be accessible from the chiral pool. An example (with limited stereoselectivity) of such an approach is the formation of a ferrocene derivative from a -pinene-derived cyclopentadiene (see Sect. 4.3.1.3 [81]). A Cj-symmetric binuclear compound (although not strictly from the chiral pool, but obtained by resolution) has also been mentioned [86]. Another possibility should be to use the central chiral tertiary amines derived from menthone or pinene (see Sect. 4.3.1.3 [75, 76]) as starting materials for the lithiation reaction. In these compounds, the methyl group at the chiral carbon of iV,iV-dimethyl-l-ferrocenyl-ethylamine is replaced by bulky terpene moieties, e.g., the menthane system (Fig. 4-2 le). It was expected that the increase in steric bulk would also increase the enantioselectivity over the 96 4 ratio, as indicated by the results with the isopropyl substituent [118]. However, the opposite was observed almost all selectivity was lost, and lithiation also occurred in the position 3 and in the other ring [134]. Obviously, there exists a limit in bulkiness, where blocking of the 2-position prevents the chelate stabilization of the lithium by the lone pair of the nitrogen. 

---