Phosphinooxazoline ligands

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-... 

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. 

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]. 

Oxazolines are another important class of ligands with a nitrogen donor group [87]. They can be regarded as cychc imines [70]. Phosphinooxazoline ligands [38,88-92] are of course the... 

A phosphinooxazoline ligand has been utilized to control enantioselectivity with success. It is determined that overall platinum catalyst generally give better regioselectivity than palladium towards products containing more electron-deficient double bonds. ... 

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. 

A Comparative Molecular Field Analysis of an Asymmetric Diels-Alder reaction with Catalysts Containing Bisoxazoline or Phosphinooxazoline Ligands,/. Org. Chem. 2003, 68, 4648-4656. 

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. 

A series of new phosphinooxazoline ligands have been recently prepared and tested in the asymmetric Heck reaction. Synthesis of the ligands involved the aromatic nucleophilic substitution of aryl fluorides with phosphide nucleophile generated from the corresponding phosphine and KHMDS (eq 49). The reaction proceeded in good yields, but proved to be more sluggish with electron-rich aryl fluorides and failed completely when the addition of electron-deficient phosphines was attempted. 

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.

Hashimoto et al. [38] reported the synthesis of the P,N oxazoline-containing ligand 59 derived from ds-2-amino-3,3-dimethyl-l-indanol and its application to the intermolecu-lar Mizoroki-Heck reaction. Their best reaction conditions for arylation of various cy-cloalkenes (Scheme 11.23) showed conversions of up to 91% and enantiomeric excesses of up to 98% for the reaction of cyclohexenyl triflate (35) with 2,3-dihydrofuran (1). Reactions using 4,7-dihydro-l,3-dioxepin (46) as the substrate proved less successful, with low conversions of 37% achieved, albeit with high enantiomeric excesses of up to 90%. In all cases, low amounts of isomerization were observed. These results are consistent with, if not better than, many analogous phosphinooxazoline ligands. 

Hou et al. [50] prepared phosphinooxazoline ligands 83 where the oxazoline substituent is at the benzylic position. The difference between these ligands and the PHOX ligands 45 is that the chelate formed with palladium is seven membered. In the reaction of phenyl trifiate (2) with 2,3-dihydrofuran (1), ligand 83b proved the most snccessful, with high... 

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). 

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