Phosphinooxazolines ligands , chiral

Asymmetric Catalysis The Beginnings with Phosphinooxazolines as Chiral Ligands... 

Lipkowitz, K.B. and Pradhan, M. (2003) Computational studies of chiral catalysts a comparative molecular field analysis of an asymmetric Diels—Alder reaction with catalysts containing bisoxazoline or phosphinooxazoline ligands. /. Org. Chem., 68, 4648. 

Castro, J., Moyano, A., Pericas, M. A., Riera, A., Alvarez-Larena, A., Piniella, J. F. Acetylene-Dicobaltcarbonyl Complexes with Chiral Phosphinooxazoline Ligands Synthesis, Structural Characterization, and Application to Enantioselective Intermolecular Pauson-Khand Reactions. J. Am. Chem. Soc. 2000,122, 7944-7952. 

Linton and Kozlowski have installed quaternary centers at oxindole C3 in enantioselective fashion via the Pd-catalyzed rearrangement of 2-allyloxy indoles (Scheme 2) [16]. For example, indole 7 underwent an enantioselective Meerwein-Eschenmoser-Claisen rearrangement in the presence of Pd(SbF6)2 and the chiral phosphinooxazoline ligand 8 to afford oxindole 9 in 89% yield and 89% ee. A two-point coordination of the chiral palladium catalyst to the C3 carbonyl and C2 oxygen (6-membered coordination system) has been proposed to rationalize the enantioselectivity of the transformation. Modest to good enantioselectivities were also observed for a series of bisphosphine chiral ligands. 

Gationic iridium complexes with chiral phosphinooxazoline ligands in ILs such as [G4GiIm]BF4 catalyze the biphasic enantioselective hydrogenation of A-(l-phenylethylidene)aniline. The products were readily isolated from... 

Scheme 11.22 Phenylation of 2,3 dihydrofuran (1) using chiral phosphinooxazoline ligands 54 and 55.

Shibasaki (Equation 19.36) and Overman first reported the enantioselective Heck reaction. A few substrate combinations react intermolecularly with high enantiose-lectivity (Equation 19.37),but most enantioselective Heck reactions used in S)mthetic applications have been conducted intramolecularly. The asymmetric Heck reaction in Equation 19.37 has begun to be a test-bed for new chiral ligands. Although most Heck reactions that occur with high enantioselectivity have been conducted with BINAP as ligand, a phosphinooxazoline ligand has been used successfully (vide infra). Overman has applied an intramolecular version of the Heck reaction to form oxindoles (Equation 19.38) in the synthesis of a variety of natural products. ... 

Iridium-Phosphinooxazoline Catalysts. Asymmetric hydrogenation of simple olefins with chiral Rh or Ru catalysts generally shows low reactivity and unsatisfactory enantioselectivity (198,248,249). However, several unfunctionalized olefins can be hydrogenated in high yields and excellent enantioselectivity by using iridium catalysts with chiral phosphinooxazoline ligands (60,186,187, 189,191-194,250) (Fig. 56). To avoid catalyst deactivation, the extremely weakly coordinating anion tetrakis[3,5-bis(trifiuoromethyl)phenyl]borate has to be used (182,251). 

In 2000, Nakano et al. developed N-P type ligand, chiral phosphinooxazoline (POZ) (59) and found that the Pd complexes (61a-c) of ligand (59) works as an effective catalyst of asymmetric ally lie alkylation (Schemes 16.17 and 16.18) [19]. Recently, they have reported that cationic Pd- and Pt-POZ (59) catalysts are effective in Diels-Alder reactions on various substrates. The cationic Pd-POZ (59) complex (61c) provided particularly excellent enantioselectivity up to 98% ee in the Diels-Alder reactions of cyclopentadiene with acryloyl (15a), crotonoyl (15b), and fumaroyl-oxazolidinones (15c) (Scheme 16.18). The Pd and Pt complexes with POZ ligands that they explored have a characteristic structure therefore, they should prove useful not only for other Diels-Alder reactions but also for other asymmetric processes. 

A number of P-N ligands has been reported as efficient ligands for the asymmetric hydrosilylation of ketones. We mention the phosphinooxazolines developed by Helmchen, Pfaltz, and Davis, we have seen before and mixed ligands containing planar-chiral heterocycles such as ferrocene [31] (Figure 18.17). For several ketone and silane combinations e.e. s in the high nineties were obtained. 

Figure 18.17. Ferrocene-based chiral-planar P-N ligand, and phosphinooxazolines [32]...

Initial studies with iridium complexes derived from chiral phosphinooxazolines (PHOX ligands) and (E)- ,2-diphenyl-1-propene as substrate gave encouraging results (Scheme 1) [5, 15]. With 4 mol% of catalyst (X = PFs ) at 10-50 bar hydrogen pressure, up to 98% ee could be obtained. However, the turnover numbers were disappointingly low. 

Allylic acetates in conjunction with phosphinooxazolines (PHOX) as chiral ligands were used for the first asymmetric Ir-catalyzed allylic substitution (Scheme 9.7) [5]. The reaction was slow, compared to that catalyzed by the [lr(COD)Cl]2/P(OPh)3 system or the parent complex [lr(COD)Cl]2, although both regioselectivity and enantioselectivity were very high. The aminations were generally slow, yet quite interesting results were achieved in intramolecular aminations nevertheless [17, 18] in particular, a very strong influence of halide salts was found. 

The moderate Lewis acidity of ruthenium complexes was used to promote catalytic Diels-Alder reaction of dienes and acrolein derivatives [21-23]. The enantioselective Diels-Alder reaction of methacrolein with dienes was catalyzed with cationic ruthenium complexes containing an arene or cyclo-pentadienyl (Cp) ligand and a chiral ligand such as phosphinooxazoline, pyridyl-oxazoline, monoxidized 2,2 -bis(diphenylphosphino)-1, T-binaphthyl (BINPO)or l,2-bis[bis(pentafluorophenyl)phosphanyloxy]-l,2-diphenylethane (BIPHOP-F). The reaction gave the cycloadduct in high yields with excellent... 

An ideal chiral ligand should not only be easily accessible but it should also be possible to modify its structure systematically. In this way the catalyst structure can be optimized for a specific application or substrate structure. Therefore, it is not surprising to see a clear trend toward modular ligands that can be readily assembled from a large selection of simple precursors. Good examples of such modular ligands are salens, phosphinooxazolines or TADDOLS, which are derived from inexpensive chiral diamines, amino alcohols and tartrate, respectively. 

The search for more reactive and more stable catalysts that overcome these limitations has led to chiral phosphinooxazoline (PHOX) ligands such as 54 [67, 68, 69, 70, 71, 72]. Several short and efficient synthesis have been developed, making these ligands readily accessible from commercially available precursors. Compared to C2-symmetric ligands, the phosphinooxazolines provide an additional means of controlling the selectivity based on electronic effects. In contrast to allyl complexes with C2-symmetric ligands, complexation of the metal by P,N-... 

Compared to very extensive studies on Heck reactions, examples of successful asymmetric Heck reactions (abbreviated to AHR in this section) are rather limited, showing that AHRs are not easy to carry out, and careful tuning of conditions is crucial. Most of the HRs proceed by using monodentate ligands. On the other hand, chiral bidentate ligands are mainly required for AHRs. This may be a reason for the difficulty in achieving efficient AHRs. The ligands most extensively used are BINAP, its derivatives, and phosphinooxazolines [116]. 

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