Phosphino-oxazolines

Phosphino-oxazoline)copper complex 28 was found by Helmchen et al. to be an excellent Diels-Alder catalyst [37] (Scheme 1.47, Table 1.20). The nitrogen atom acts as an electron-donating ligand, whereas phosphorus is a cr-donor-Tt-acceptor ligand. The copper complex of this phosphino-oxazoline ligand is therefore expected to have... 

Scheme 9.13 Ru-catalysed reduction of acetophenone with phosphino-oxazoline ligands.

Various phosphino oxazoline ligands were designed, and they can also be optimized via high-throughput catalyst screening for certain applications. In (244), a near square planar environment with two nitrogen atoms in a cis position relative to each other is observed.6 9... 

Helmchen and coworkers employed a,co-amino-1,3-dienes as substrates [51]. By using palladium complexes with chiral phosphino-oxazolines L as catalysts, an enantiomeric excess of up to 80 % was achieved. In a typical experiment, a suspension of Pd(OAc)2, the chiral ligand L, the aminodiene 6/1-90 and an aryltriflate in dimethylformamide (DMF) was heated at 100 °C for 10 days. Via the chiral palladium complex 6/1-91, the resulting cyclic amine derivative 6/1-92 was obtained in 47% yield and 80% ee (Scheme 6/1.23). Using aryliodides the reaction time is shorter, and the yield higher (61 %), but the enantiomeric excess is lower (67% ee). With BINAP as a chiral ligand for the Pd°-catalyzed transformation of 6/1-90 and aryliodide, an ee-value of only 12% was obtained. 

Recent developments in chirality induced by ligands, and in efficient synthetic methods for ligands such as diphosphines, chiral diamines, amino-phosphine-phosphinites, phosphino-oxazolines and diimino-diphosphines, are available in the literature.105-107... 

The oxazoline-derived P,N ligands can be classified into four groups according to structure phosphino-oxazolines phosphite- and phosphinite-oxazolines catalysts containing a P-N bond and structurally related non-oxazoline catalysts. 

The most extensively studied of these systems are the phosphino-oxazoline (PHOX) catalysts 14 (Fig. 29.2). Good enantioselectivity has been achieved with these catalysts over a broad range of substrates [7]. 

DCM dichloromethane PHOX phosphino-oxazoline r.t. room temperature THF tetrahydrofuran TOF turnover frequency... 

The phosphino-oxazoline copper(II) complex (55) has also been found to be an effective catalyst[136] as have some titanium complexes, such as the extensively researched titanium-TADDOL system (56)[137]. A modified Ti(IV)-TADDOL compound is the catalyst of choice to promote Diels-Alder cycloaddition reactions between cyclopentadiene and alk-2-enyl phenylsulfonylmethyl ketones[138]. 

Heck reactions have also been used by Helmchen et al. for a two-component domino process of a,co-amino-1,3-dienes.1721 By using palladium complexes with chiral phosphino-oxazolines as catalysts an enantiomeric excess of up to 80 % is achieved. In a... 

Synthesis and application of heterocyclic phosphino oxazoline (hetphox)... 

SYNTHESIS AND APPLICATION OF HETEROCYCLIC PHOSPHINO OXAZOLINE(HetPHOX) IRIDIUM COMPLEXES FOR THE ASYMMETRIC HYDROGENATION OF ALKENES... 

Phosphino-oxazoline)/Cu(II) complexes with bulky aryl groups at phosphorus were found to be excellent for a similar asymmetric cycloaddition reaction [39] (Eq. 8A.20). Enantioselectivity up to 79% ee was achieved in the cycloaddition of cyclohexadiene and acryloyl oxazolidinone. 

Chiral chelating ligands that contain only one phosphine and another donor atom have been successful in recent years. A readily synthesized example is the phosphino-oxazoline ligand 87 shown in Scheme 31. These types of ligand can be prepared in two steps from an amino alcohol, a substituted benzonitrile and either a electrophillic or nucleophilic phosphorus reagent. They have been used in a number of asymmetric reactions. 

On the other hand, palladium(0)-catalyzed allylic animation of racemic ( )-l,3-diphenyl-2-propenyl-l-acetate with the sodium salt of 4-toluenesulfonamide in the presence of phosphino-oxazoline F works very well and affords 14 [96% yield configuration presumably (7 )] of 97% enantiomeric excess, as determined by HPLC77. Remarkably, ligand F also enables a highly enantioselcctivc (up to 90% cc) allylic substitution of racemic 1,3-dialkyl substituted 2-propcnyl-1-carbonates and phosphates using the sodium salt of 4-toluenesulfonamide as nucleophile77. 

Tridentate salen ligands (10) derived from 1 have given excellent results in the enantiocontrol of the hetero Diels-Alder addition reaction of dienes with aldehydes (eq 7) and in the asymmetric additions of TMS-azide to mc5o-epoxide and trimethylsilyl cyanide to benzaldehyde (up to 85% ee). Phosphino-oxazolines derived from 1 have been employed for the asymmetric control of palladium-catalyzed allylic substitution reactions products of 70-90% ee were obtained. Photolysis of crystalline adducts of enantiomerically pure 1 with prochiral alcohols results in asymmetric inductions of up to 79% in a rare example of a solid-state enantioselective reaction. ... 

Handling, Storage, and Precautions Phosphino oxazolines of this type are sufficiently stable to be handled in air. For longer periods of time, they should be stored at —20 °C under argon. 

Selective lithiation of alkyl- or aryl-pyridines is the key to the synthesis of a range of new phosphinopyridine ligands, e.g., (5), (6), and a fused phosphinomethylpyridinoferrocene. A similar approach has been used in the synthesis of chelating phosphino-oxazoline ligands, e.g.,... 

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