Phosphinooxazoline

Scheme 7.5 Heck reactions of dihydrofuran with phenyl- or cyclohexenyl-triflates with (benzo)thiophene-containing phosphinooxazoline ligands.

As an extension of this methodology, thiophene-containing phosphinooxazoline ligands were applied to the intramolecular version of the Heck reac-... 

G. Helmchen, A. Pfaltz, Phosphinooxazolines - A New Class of Versatile, Modular RN-Ligands for Asymmetric Catalysis, Acc Chem. Res. 2000, 33, 336-345. 

Helmchen and co-worker investigated the use of phosphinooxazolines as ligands for copper(II) catalyzed Diels-Alder reactions (Scheme 19) (214). Optimal selectivities are found for a-naphthyl-substituted phosphinooxazoline (299). These catalysts require 2.5 h to induce complete conversion to cycloadduct, compared to 18 h using the triflate complex 269c under identical conditions. Helmchen invokes a square-planar metal geometry to explain the stereochemistry of the adducts, similar to the model proposed by Evans. He suggests that the bulky phosphine substituents are required to orient binding of the dienophile in such a way as to place the olefin directly below the terf-butyl substituent on the oxazoline. 

Scheme 19. Phosphinooxazoline-Cu ) catalyzed Diels-Alder reaction. [Adapted from (214).]...

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. 

Schrems et al. identified a number of P,N ligands, which have given encouraging results for this class of substrate [70]. Surprisingly, the structurally simple readily accessible phosphinooxazoline 12a, originally reported by Sprinz and Helmchen [71], and subsequent analogs 12b-e proved to be the most efficient ligands for several substrates (Table 8). 

The first enantioselective, iridium-catalyzed allylic substitution was reported by Helmchen and coworkers soon after the initial report by Takeuchi. Helmchen studied catalysts generated from phosphinooxazoline (PHOX) ligands and [Ir(COD)Cl]2 for the reactions of sodium dimethylmalonate with cinnamyl acetates (Scheme 2) [50]. The alkylation products were isolated in nearly quantitative yield and were formed with ratios of branched-to-Unear products up to 99 1 and with enantioselectivities up to 95% ee. In this and subsequent studies with PHOX ligands [51,52], Helmchen et al. demonstrated that the highest yields and selectivities were obtained with a PHOX ligand containing electron-withdrawing substituents and... 

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

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. 

Alkylative desymmetrization of cyclic anhydrides would be an attractive alternative to this chemistry since the product would be a keto-acid and would allow elaboration of the molecular scaffold. The first catalyzed asymmetric alkylative desymmetrization of a cyclic anhydride was published from our laboratories in early 2002. The phosphinooxazoline ligand t-PrPHOX provided an effective catalyst when bound to nickel, affording keto-acid 179 in 85% yield and 79% ee ... 

Larsen, J., Rasmussen, B.S., Hazell, R.G. and Skrydstrup, T, (2004) Preparation of a novel diphosphine-palladium macrocyclic complex possessing a molecular recognition site. Oxidative addition studies. Chem, Commun., 202-203 Braunstein, P., Clerc, G. and Morise, X. (2003) Cyclopropanation and Diels-Alder reactions catalyzed by the first heterobimetallic complexes with bridging phosphinooxazoline ligands. New J. Chem., 27,68-72 Braunstein, P., Clerc, G., Morise, X., Welter, R. and Mantovani, G. (2003) Phosphinooxazolines as assembling ligands in heterometallic complexes. Dalton Trans., 1601-1605. 

Despite the success in the 1,3-diphenylallyl system, use of many of these ligands in the alkylation of 1,3-dialkylallyl system as Equation 8E.4 has produced mixed results, as summarized in Table 8E.5. With the phosphinooxazoline-type ligands, good selectivities (>90% ee) are still obtained from the reactions of substrates possessing bulky allylic substituents such as isopropyl groups (entries 8-10), but smaller substrates such as 1,3-dimethylallyl derivatives give only a modest level of enantioselectivities (entries 1 -7). The disparity between these results appears to be sterically derived as the enhanced preference of syn versus anti orientation in the 7t-allyl structure by the bulky phenyl or isopropyl groups may not be present with the smaller substrates. 

Modifying the parent phosphinooxazoline 38 to ligand 57, exciting improvement in the regio- and enantioselectivity has been realized (entries 1 and 2) [151,152]. Similar enantio- and regioselectivities obtained from the reaction of the racemic substrate 125 suggest a facile... 

Phosphinocarbenes, with tungsten carbonyls, 5, 678 Phosphino ligands, on Ti(IV) mono-Cp complexes, 4, 393 Phosphinomethanides, with Zr(IV), 4, 789 Phosphinooxazolines, in allylic ester alkylations, 11, 83—86 0-Phosphinophenoxo ligands, on mono-Cp Ti(IV) complexes, 4, 487... 

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. 

Palladium complexes with phosphinooxazoline ligands such as 2 have been proven to be very efficient catalysts for the coupling of alkynes to enynes in solvent-free reactions (Scheme 8) and provided an efficient tool for regiocontrolled cross-coupling reactions between mono- and disubstituted alkynes [27]. 

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