Fluorous chiral

Figure 4. Structure of fluorous chiral Co(salen) catalysts 6-8.

Cavazzini, M. Quid, S. Pozzi, G. (2002) Hydrolytic kinetic resolution of terminal epoxides eatalyzed by fluorous chiral Co(salen) complexes. Tetrahedron 58 3943-3949. 

More examples are found for varied oxidation processes mainly for various epoxidations carried out by metal catalysts bearing F-modified ligands, such as porphyrins,139 Ru perfluoroacetylacetonate salt,140 or salen complexes,141 142 or using the 3 selenium compound as catalyst.143 The potential for enantioselective transformations offering an easy way to recover precious chiral reagents and catalysts was demonstrated in enantioselective epoxidation using fluorous chiral salen... 

The enantioselective synthesis of a-amino acids employing easily available and reusable chiral catalysts or reagents presents clear advantages for large-scale applications. Accordingly, recyclable fluorous chiral phase-transfer catalyst 31 has been developed by the authors group, and its high chiral efficiency and reusability demonstrated in the asymmetric alkylation of 2. After the reaction, 31 could be easily recovered by simple extraction with FC-72 (perfluorohexanes) as a fluorous solvent and used for the next run, without any loss of reactivity and selectivity (Scheme 5.17) [23]. 

The hydrogen-transfer reduction of acetophenone under FBS conditions was also readily achieved in the presence of fluorous chiral diamines, diimines and (3-amino alcohols derived from tartaric acid (e.g. 18-20 Scheme 5.5) in combination with [Ir(COD)Cl]2 or Rii(p-cyrricri(jCJJ, [42], but much lower enantioselectivities (up to 31% ee in the case of 18/[Ir(COD)Cl]2) were obtained. 

The first example of a fully recyclable fluorous chiral metal-free catalyst was reported by Maruoka and coworkers, who described the enantioselective alkylation of a protected glycine derivative (Scheme 5.17) with various benzyl- and alkyl bromides, in the presence of the quaternary ammonium bromide 62 as a phase-transfer catalyst [77]. Reactions were performed in a 50% aqueous KOH/toluene biphasic system in which 62 was poorly soluble. Nevertheless, the alkylated products were obtained in good yields (from 81 to 93%), with enantioselectivity ranging from 87 to 93% ee. Catalyst 62 was recovered by extraction with FC-72, followed by evaporation of the solvent, and could be used at least three times without any loss of activity and selectivity. 

Scheme 11.7 Recyclable fluorous chiral phase-transfer catalyst.

Fluorous chiral binaphthol ligands have been used for enantioselective addition of diethyl zinc to aldehydes in a biphasic system [20] (Scheme 3.5). 

The use of fluorous chiral manganese salene (Jacobsen-Katsuki) catalysts (29, 30) [30] in combination with different oxidants enables enantioselective epoxidation of olefins [31] in high yields and with moderate to high enantiomeric excess (Scheme 3.12). 

Asymmetric transfer hydrogenation of ketones in the presence of soluble transition metal catalysts has been developed [8-10], enantioselectivities up to 99% ee being obtained using a ruthenium catalyst bearing mono-N-tosylated diphenyl-ethylenediamine as a ligand. Iridium complexes associated with fluorous chiral diimines 3a-3c or diamines 4a—4b have also been shown to be effective catalysts in hydrogen-transfer reduction of ketones [11,12]. 

Takeuchi, Curran, and co-workers synthesized a fluorous chiral diol, (R)-2,2 bis[(S)-2-hydroxy-2-phenylethoxy]-6,6 -bis[tris(lH,lH,2H,2H-perfluorooctyl)silyl]-l,T-binaphthyl ((R,S)-FDHPEB) (F content = 56%, partition coefficient benzene/ FC-72 = 1 32, THF/FC-72 = 19 1) and applied it to a Sml2-mediated enantio-selective protonation of 2-methoxy-2-phenylcyclohexanone [2], The reaction was carried out under the same reaction conditions as those of the original nonfluorous reaction [3], In the original reaction, the product was separated from the nonfluorous chiral proton source (2 equiv realtive to the substrate) with preparative TLC to give the product in 70% chemical yield and 87% ee. In the fluorous version, the product and the fluorous chiral proton source were separated by FC-72 extraction (six times) and more simply by fluorous solid-phase extraction with an FRP silica gel column. 

Pozzi, Sinou, and co-workers prepared a fluorous chiral phosphine, (R)-2- bis[4-(1 H,1 H-perfluorooctyloxy)phenyl]phosphino -2 -(l H,1 H-perfluorooctyloxy)-l, 1 -binaphthyl (F content = 52%, partition coefficient n-perfluorooctane/toluene = 0.23, n-perfluorooctane/CHjOH = 7.42) and used for a chiral ligand of palladium complex in an asymmetric aUyHc alkylation of 1,3-diphenylprop-2-enyl acetate [8]. The reaction was carried out at room temperature in BTF or toluene and gave the corresponding product in 99% and 88% chemical yields and 81% ee and 87% ee, respectively after the nonfluorous MOP complex gave the product in 95% yield and 99% ee in toluene at 0 °C [9]) [Eq. (1)]. When toluene was used as a solvent, the simple extraction of the reaction mixture with n-perfluorooctane (twice) allowed the complete removal of the ligand and of the palladium complex. However, the recovered palladium complex did not have catalytic activity for the reachon. 

The reaction rate was about one-third of that in the original reaction. The products and the fluorous chiral ligand were separated by FRP silica gel and about 70% of the chiral ligand was recovered. However, the compound recovered was FjjBlNAPO and could not be re-used for the next reaction. 

The examples on fluorous chiral phosphine ligands described above indicate that finding a chiral phosphine ligand effective for recycling it by fluorous techniques... 

Two new fluorous chiral 2,2 -bis(diphenylphosphino)-1,1 -binaphthyl (BINAP Table 15.1, entries 11 and 12) ligands were synthesized and their efficiency was demonstrated in an asymmetric Mizoroki-Heck reaction (Scheme 15.8) [74-76]. Aryl triflates 38 were coupled with 2,3-dihydrofuran (39) to (i )-40 in up to 93% ee. Either pure fluorous solvents or mixtures of fluorous and nonfluorous solvents were applied. Ligand 34 was compared with conventional BINAP, with the fluorous ligand giving lower reaction rates and a similar level of enantioselectivity in 24-77 h reaction time [74, 75]. The catalyst could not be recovered by reverse-phase silica gel chromatography due to its oxidation. 

Nakamura, Y., Takeuchi, S., Zhang, S. et al. (2002) Preparation of a fluorous chiral BINAP and application to an asymmetric Heck reaction. Tetrahedron Lett., 43, 3053-6. 

Nakamura, Y, Takeuchi, S. and Ohgo, Y. (2(X)3) Enantioselective carbon xffbon bond forming reactions using fluorous chiral catalysts. J. Fluorine Chem., 120,121-9. 

In addition, in 2(X)4 Mamoka and co-workers [72] synthesized a recyclable fluorous chiral phase-transfer catalyst which was successfully applied for the catalytic asymmetric alkylation of a glycine-imine derivative followed by extractive recovery of the chiral phase-transfer catalyst using fluorous solvent. Later, in 2010 Itsuno and co-workers [73] published a new type of polymer-supported quarternary ammonium catalysts based on either cinchona alkaloids or Maruoka s-type catalyst bound via ionic bonds to the polymeric sulfonates. 

A fluorous chiral organocatalyst (18) promotes the formation of the anti-Mol product (with up to 96% ee) on reaction between aromatic aldehydes with ketones in brine. The enantioselectivity achieved on promotion of aldol and Mannich reactions by another di-diamine-based catalyst (19) can be reversed by the addition of an achiral acid and is to be the subject of further mechanistic investigation. ... 

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