Applications of Chiral Ferrocene Derivatives

This section is meant to give a short survey on the applications of chiral ferrocenes for the synthesis of (mostly chiral) organic compounds. Applications of phosphines will be treated very briefly, as they are the topic of a separate chapter of this book (Chapter 2). The same is true for the reaction of zinc alkyls with carbonyl compounds. 

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The synthesis and application of chiral ferrocene derivatives has attracted much interest.358 Hence the ferrocenyldiphosphine (163) (Josiphos) can be prepared by direct HPR2 substitution of the dimethylamino group (Equation (40)).359 Various other ferrocene-based chiral ligands are known (e.g., the TRAP ligands (164)).360-364... 

Considering the industrial importance of cyclopropanes in the pesticide field, it is not surprising that chiral ferrocenylphosphines have been applied as control ligands for the palladium-catalyzed enantioselective formation of cyclopropanes from the dicarbonate of 2-butene-1,4-diol and malonates, leading to 70% ee (Fig. 4-32e) [179]. Ferrocenylphosphines also induce chirality in the reaction of sulfonyl-substituted propenyl carbonates and acrylic esters to methylenecyclopentanes (up to 78% ee (Fig. 4-321)) [180], with potential applications in natural product synthesis. These examples show that the synthetic potential of chiral ferrocene derivatives is not yet fully exploited, and one may look forward to new applications. 

The rapid development of chiral phosphine derivatives of ferrocene was undoubtedly due to their application in catalysis. In contrast, chiral sulfur compounds from lithiated iV,iV-dimethyl-l-ferrocenylethylamine were only prepared about 15 years later [140], For the synthesis of such derivatives, the lithiated amine is treated with disulfides as shown in Fig. 4-24, top (and analogously, diselenides [141]). The sulfides obtained are easily oxidized by peracids or NaI04 to the corresponding sulfoxides. As sulfur becomes a new center of chirality by the oxidation, diastereoisomeric sulfoxides are formed in ratios depending on the oxidant [140]. If chiral oxaziridines [106, 142] are used as oxidizing agents, the diastereoisomeric ratio is appreciably... 

Synthesis and applications of sulfur-containing chiral ferrocene derivatives, particularly, ferrocene-containing p-lactams 07SL360. 

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]. 

Applications. The first widely applicable lc separation of enantiomeric metallocene compounds was demonstrated on p-CD bonded-phase columns. Thirteen enantiomeric derivatives of ferrocene, ruthenocene, and osmocene were resolved (7). Retention data for several of these compounds are listed in Table 2, and Figure 2a shows the lc separation of three metallocene enantiomeric pairs, p-Cyclodextrin bonded phases were used to resolve several racemic and diastereomeric 2,2-binaphthyldiyl crown ethers (9). These compounds do not contain a chiral carbon but still exist as enantiomers because of the staggered position of adjacent naphthyl rings, and a high degree of chiral recognition was attained for most of these compounds (9). 

However, this method suffers severely from the tedious experimental conditions leading to the sulfoxides from diol 52. Several crystallizations are required—the first to purify the tnms sulfite, a second to purify the hydroxy sulfinate, and, finally, a column chromatography to purify the sulfoxide. This may be the reason why there is no application of this method in the literature, apart from that by the same group in the sulfinylation of ferrocene,94 getting the o-lithium derivative to react with various electrophiles to afford chiral ferrocenes (Scheme 17,59 R = HOCMe2, Me, Ph2P). 

A word of caution should be added with respect to Chemical Abstracts, as far as chirality assignments of homoannular substituted ferrocene derivatives are concerned. Until the 8th collective index, only (-f) and (—) are found as chirality indicators. For quite a long time, no descriptors were given at all, only the remark stereoisomer , followed by the registry number, which does not allow identification of a compound easily. This fact is in sharp contrast to the claims of Chemical Abstracts Service authors that they would consequently use Schlogl s central descriptors [20, 21]. Since volume 114, the (R, S ) nomenclature for ferrocene derivatives begins to appear, but its application is not very consequent, at least at the time where the book was written, and it is advisible to examine the orginal article rather than trust Chemical Abstract s descriptors. 

A chiral auxiliary is a compound that is incorporated into a larger molecule, where it transmits its chirality information to newly formed chiral elements. It is cleaved from the target molecule in a later step of the reaction sequence and should in principle be recycled, to avoid loss of the precious chiral material. Among the ferrocene derivatives, chiral primary amines are typical auxiliaries for their synthesis, see Section 4.3.3. All applications involve the intermediate formation of imines with carbonyl compounds. 

Bis(cyclopentadienyl)iron derivatives, ferrocenes, are remarkably stable against heat and air and undergo various kinds of chemical reactions. They are usually prepared by the reaction of FeCh with an alkali metal salt of cyclopentadienyl or cyclopentadiene in the presence of base [51]. Although ferrocene derivatives basically have chemical reactivities similar to those of aromatic compounds, they have found only limited applications to organic synthesis so far. However, because chiral ferrocenylphosphines are capable of having both planar chirality and an asymmetry in the side chain in their rigid framework, they have been used recently in a number of asymmetric reactions. In this section, synthesis and developments of monocyclopentadienyl complexes and ferrocenylphosphines are described. The general chemistry of ferrocenes and half metallocene complexes is reviewed elsewhere [52-53]. 

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