Ferrocenes enantioselective synthesis

Phosphine ligands based on the ferrocene backbone are very efficient in many palladium-catalyzed reactions, e.g., cross-coupling reactions,248 Heck reaction,249 amination reaction,250 and enantioselective synthesis.251 A particularly interesting example of an unusual coordination mode of the l,l -bis(diphenylphosphino)ferrocene (dppf) ligand has been reported. Dicationic palladium(II) complexes, such as [(dppf)Pd(PPh3)]2+[BF4 ]2, were shown to contain a palladium-iron bond.252,253 Palladium-iron bonds occur also in monocationic methyl and acylpalladium(II) complexes.254 A palladium-iron interaction is favored by bulky alkyl substituents on phosphorus and a lower electron density at palladium. 

Chiral ferrocenes form a class of powerful and useful chiral hgands, and a number of methods are available for their enantioselective synthesis. The introduction of a second substituent via directed metallation is a simple and powerful way to make disubstituted ferrocenes with planar chirality from simple, achiral monosubstituted ferrocenes. Chiral... 

Enantioselective synthesis of /3-amino alcohols by Sml2-mediated cross-pinacol coupling of the planar chiral iV-sulfonyl(ferrocenylidene)amine with ferrocene carboxaldehyde is achieved by facile reduction of the ferrocenyli-dene amine with Sml2, followed by enantioselective addition to the aldehyde (Equation (75)). ... 

Enantioselective Synthesis of (+)-(,SVV)-1,1 -Bis[2-(benzyloxycarbonyl)-2-(Boc-amino)ethyl]ferrocene... 

Cyclometallated iridium complexes, for OLEDs, 12, 145 Cyclometallated palladium(II) complexes from amines and pyridines, 8, 280 with C,C-chelating ligands, 8, 291 enantioselective synthesis, 8, 296 ferrocene-based palladacycles, 8, 292 four-membered palladacycles, 8, 297 imine- and oxime-based complexes, 8, 285 with N-N and N=N bonds, 8, 288 palladacycle catalysis, 8, 297... 

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. 

Some of the substituted ferrocenes can be chiral118 and find uses in asymmetric catalysis, enantioselective synthesis, and in diverse materials science areas. 

Table 5.2 Enantioselective synthesis of planar chiral ferrocene via C—H functionalization reported by Gu and Vbu. ...

The electrophiles introduced provide diverse carbon- and heteroatom-based chiral ferrocenes, some of which are related to popular ligands currently used in small- and large-scale enantioselective catalysis. In extension of the methodology, a direct and highly efficient enantioselective synthesis of C2-symmetric... 

In 2005, Riant et al. reported the synthesis of a new air-stable S/N-chelating zinc catalyst, depicted in Scheme 10.50, which was fully characterised by all spectroscopic methods. This complex, prepared from the corresponding ferrocene oxazoline, was applied to the enantioselective hydrosilylation of ketones in the presence of polymethylhydrosiloxane, PMHS, providing modest enan-tioselectivities (<55% ee). ... 

Unfortunately, the presence of stereoisomers does not allow this class of compounds to proceed directly into clinical trials. There is hope that future synthesis using chiral bases like sparteine may allow enantioselective preparation of titanocene dichloride derivatives and not only ferrocenes [30]. Additionally, further reaction pathways leading to achiral titanocenes have to be explored. 

The chiral vinylferrocene monomer 18 and the chiral copolymers 19a — e have been prepared for the first time. Insolubilization of the chiral ferrocene catalyst lowered the enantioselectivity to some extent compared with that of the soluble monomeric catalysts. Nevertheless, polymers 19a —e are usefull for the enantiose-lective synthesis of secondary alcohols. 

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... 

If an achiral ferrocene derivative is converted to a chiral one by chiral reagents or catalysts, this may be called an asymmetric synthesis. All asymmetric syntheses of ferrocene derivatives known so far are reductions of ferrocenyl ketones or aldehydes to chiral secondary alcohols. Early attempts to reduce benzoylferrocene by the Clemmensen procedure in (5)-l-methoxy-2-methylbutane as chiral solvent led to complex mixtures of products with low enantiomeric excess [65]. With (25, 3R)-4-dimethylamino-l,2-diphenyl-3-methyl-2-butanol as chiral modifier for the LiAlH4 reducing agent, the desired alcohol was formed with 53% ee (Fig. 4-9 a) [66]. An even better chiral ligand for LiAlH4 is natural quinine, which allows enantioselective reduction of several ferrocenyl ketones with up to 80% ee [67]. Inclusion complexes of ferrocenyl ketones with cyclodextrins can be reduced by NaBH4 with up to 84% enantioselectivity (Fig. 4-9 b) [68 — 70]. 

A chiral C2-symmetric bridged ferrocene was constructed from a synthetic ligand containing two cyclopentadiene units (Fig. 4-12d). The key step in the synthesis of the ligand is a diastereoselective Diels — Alder reaction of anthracene with bis[(S)-l-ethoxycarbonylethyl]fumarate. When oxidized to the ferrocinium salt, the ferrocene derivative has Lewis acid properties and catalyzes Diels — Alder reactions with some enantioselectivity [85]. 

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. 

Enantiopure diaryl methanols (1) are important intermediates for the synthesis of biologically active compounds.[1] Here, a synthetic approach which employs aromatic aldehydes and readily accessible and commercially available aryl boronic acids is reported.[2,3] The catalysis with planar chiral ferrocene (2)[4] yields a broad range of optically active diaryl methanols with excellent enantioselectivities. Upon addition of DiMPEG (dimethoxy polyethyleneglycol) to the reaction mixture the enantioselectivity is increased. 

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