Stereoselective reactions of ferrocenes

The photochemical reaction of alkoxychromium(0)carbene complexes and ferrocene mono- and disubstituted imines have been reported to form 2-azetidinones having one or two ferrocene moieties in good yields [136]. The chromium(0) carbene complex reacted smoothly with ferrocene imines that allowed to place ferrocene substituents at the N-l, and the C-4, or simultaneously at the N-l and the C-4 positions of the (3-lactam ring, with cis stereoselectivity (Scheme 71). 

Catalytic reactions have the advantage over the methods discussed so far in that the chiral catalyst need not be added in stoichiometric amounts, but only in very small quantities, which is important if not only the metal (very often a precious one) but also the chiral ligand are expensive. Among the ferrocenes, phosphines are by far the most important catalysts for stereoselective reactions, and are covered in Chapter 2 of this book. We will therefore focus here mainly on the catalytic applications of chiral ferrocenes not containing phosphine groups. Only recently, some progress has been made with such compounds, mainly with sulfides and selenides, and with amino alcohols in the side chain (for this topic, see Chapter 3 on the addition of dialkyl zinc to aldehydes). 

Introduction of the tricarbonylchromium group into cyclophane chemistry has great potential for the preparation of planar- (or helical-)chiral compounds. Besides structure/chiroptics relationships, carrying out stereoselective reactions is of major importance. Recently, inclusion of ferrocenes and benzene-Cr(CO)3 into the cavity of a cyclodextrine was achieved and this makes the connection to supramolecular chemistry [183]. 

Reaction of the isodicyclopentadienide anion (11) with Fe affords stereoselectively the ferrocene derivative (12) through... 

Pd(OAc)2 and l,l -bis(diisopropylphosphino)ferrocene (DzPPF) (toluene, 60 °C, 2 h) as the optimized reagents and conditions for the eompletely p-stereoselective, preparation of C-glycosyl derivatives type 6 (Seheme 2). This reaction was applied to the stereoselective preparation of a range of p-C-glycosyl derivatives 6a-e, which could be obtained in moderate to good yields (Scheme 2). ... 

As the latter were not easily accessible by chemical synthesis at that time, new methods of preparing these ferrocene derivatives were developed and introduced in 1969. It was then proved that the U-4CRs of chiral a-ferrocenyl-alkylamines can form diastereomeric a-aminoacid derivatives stereo-selectively, and it was further shown that after the reaction the a-ferrocenyl groups of the products can be replaced by protons, thus resynthesizing the chiral a-ferrocenyl-alkylamines simultaneously." Later, the development of this ferrocene chemistry was given up since such syntheses cannot form the products in sufficient quantity and stereoselective purity. ... 

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. 

Asymmetric ferrocene-derived biphosphines have been utilized in a variety of catalytic asymmetric reactions, but only one application to enamide hydrogenation is reported (54). This is of interest because the acid is reduced in much higher optical yield than its methyl ester, and stereoselectivity is drastically reduced by triethylamine. It implies that hydrogenbonding between the bound carboxylic acid of the enamide and the... 

---