Catalyst azaferrocene

Later, several other copper catalysts bearing dinitogen ligands [bipyridine derivatives (76),232,233 diamines (77),234 bis(azaferrocene) (78),235 bisferrocenyldiamine (79),159 and bis(oxazoyl) binaphthyl (80)236] have been introduced (Scheme 62), but asymmetric induction by them does not exceed that by complex (75). 

In the 1990s, short peptides,and other nucleophiles °° ° were used as organocatalysts for a number of enantioselective acyl transfer processes transformations that set the stage for the more recent research in the area of nucleophilic catalysis.One of the most appealing approaches to enantioselective acyl transfer was outlined by Fu using an azaferrocene catalyst (6) [Eq. (11.6)]. While these pyridyl systems are not organic catalysts in the strictest sense, these azaferrocene compounds function as chiral dimethylaminopyridine equivalents for a broad range of acyl transfer processes ... 

The first class of amine-based nucleophilic catalysts to give acceptable levels of selectivity in the KR of aryl alkyl. yec-alcohols was a series of planar chiral pyrrole derivatives 13 and 14, initially disclosed by Fu in 1996 [25, 26]. Fu and co-workers had set out to develop a class of robust and tuneable catalysts that could be used for the acylative KR of various classes of. yec-alcohols. Planar-chiral azaferrocenes 13 and 14 seemed to meet their criteria. These catalysts feature of a reasonably nucleophilic nitrogen and constitute 18-electron metal complexes which are highly stable [54-58]. Moreover, by modifying the substitution pattern on the heteroaromatic ring, the steric demand and hence potentially the selectivity of these catalysts could be modulated. 

In addition, azaferrocene catalyst 8 has been utilized by Fu and co-workers to perform enantioselective additions of alcohols to prochiral ketenes [51]. Aryl alkyl ketenes are substituted with MeOH to give a-aryl ester products in good enantioselectivities and very good yields, with higher enantiomeric excesses obtained for products with larger alkyl groups (Scheme 12). Use of 2,6-di-f-butylpyridinium triflate as a proton shuttle substantially enhances the enanti-... 

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). 

It has also been demonstrated that a planar-chiral azaferrocene derivative of 4-(pyrrolidino)pyridine is an excellent catalyst for the enantioselective Staudinger reaction, providing P-lactams 24 with very good stereoselection and yield <02JACS1578>. 

Ferrocene analogs that possess a heteroatom in place of one carbon atom have been known for some time. The most common of these heteroferrocenes are the azaferrocenes and the phosphaferrocenes, though complexes having snlfur, boron, arsenic, antimony, bismuth, and nickel atoms are known. Review articles that are either comprehensive (in the case of phosphaferrocenes), or cover aspects of this chemistry (in the case of azaferrocenes), are available space restrictions for this review do not permit complete coverage of these areas. Instead, recent developments in the area of planar chiral heteroferrocenes, especially as it relates to asymmetric catalyst design, will be the primary focus here. 

Many other chiral copper catalysts have been reported, most of them being derived from C2-symmetrical bidentate nitrogen ligands [13, 27]. Some ligands such as the bipyridine derivatives 14 [60, 61, 62], the diamine 15 [63] and the bis(azaferrocene) 16 [64] are capable to induce high ees, but none of them can compete so far with chiral bisoxazolines in terms of high selectivity combined with effectiveness, general applicability and ease of preparation. 

The lone pair in the T] -pyrrolyI ligands is the most basic site in V azolyl complexes, and is the site of protonation and electrophilic attack. Novel planar chiral catalysts have been prepared, based on the azaferrocene unit, and these complexes have been used for asymmetric nucleophilic catalysis. One example of such a complex is shown on the left in Figure 4.5. Some linked versions of azaferrocenes possessing C synunetry create an unconventional chiral environment. The ligand on the right in Figure 4.5 has been used for several asymmetric copper-catalyzed transformations. ... 

Functionalization of Azaferrocene Catalysts. Chiral azaferrocenes are highly useful in enantioselective acylation as nucleophilic catalysts, and in transition metal-catalyzed asymmetric reactions as chiral ligands. Enantioselective lithiation of an azaferrocene moiety followed by functionalization with (TMS0)2 resulted in a lateral hydroxyl-substituted product with excellent optical purity, but in poor yield (eq 7). The low yield was attributed to the poor reactivity of (TMSO)2 toward the labile azaferrocene substrate. 

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