Butyl-2-oxazolin-2-yl

The intermolecular asymmetric Heck reaction, a palladium-catalysed carbon-carbon bond forming process, is an efficient method for the preparation of optically active cyclic compounds.[1] Very recently, a new catalytic system has been developed based on palladium complexes having l-[4-(5)-tert-butyl-2-oxazolin-2-yl]-2-(5)-(diphenylphosphino)ferrocene (1) as the chiral ligand121 (Figure 5.2), which we have shown to be efficient catalysts for the enantioselective intermolecular Heck reaction of 2,3-dihydrofuran (2).[3] In contrast to complexes derived... 

The ligand, 1 -[4-(5)-terf-butyl-2-oxazolin-2-yl]-2-(.S )-(diphenylphosphino)fcrro-cene (1), is prepared in three steps from readily available ferrocenecarboxylic acid chloride (5).[4] The steps involved are firstly amide bond formation secondly cyclisation to the oxazoline and finally diastereoselective lithiation/phosphinylation to afford (1) (Figure 5.4). 

After filtration through a Buchner funnel, the filtrate was washed well with water (100 mL) and brine (100 mL) to remove excess triethylamine and was then dried over anhydrous magnesium sulfate. The solvent was then removed to give a brown residue which was dissolved in dichloromethane (3 mL) and purified by column chromatography (silica, petroleum ether 40-60 °C/ethyl acetate 70 30) to give [4-(S)-ferf-butyl-2-oxazolin-2-yl]ferrocene, (1.01 g, 90%), as an orange solid, m.p. 137-138 °C. 

SYNTHESIS OF l-[4-(8>tert-BUTYL-2-OXAZOLIN-2-YL]-2-(S)-(DIPHENYLPHOSPHINO)FERROCENE (1)... 

Notes This procedure has been scaled up to provide 5 g of l-[4-(S)-tert-butyl-2-oxazolin-2-yl]-2-(S)-(diphenylphosphino)ferrocene. 

A solution of phenyl trifluoromethanesulfonate (30.0 mg, 0.13 mmol) and n-tridecane (10.0 mg, 0.054 mmol) in either toluene (0.5 mL) or benzene (0.5 mL) was added to a 5-mL Schlenk tube containing Pd2(dba)3 (2.3 mg, 0.004 mmol) and 1 -[4-(5)-terf-butyl-2-oxazolin-2-yl]-2-(5)-(diphenylphosphino)ferrocene (3.96 mg, 0.008 mmol) under an atmosphere of nitrogen. To this was added 2,3-dihydrofuran (46.2 mg, 0.65 mmol) and base (0.39 mmol) (Table 5.5). The resulting solution was degassed by three freeze-thaw cycles at 0.01 mbar and left to stir under nitrogen at 80 °C for 14 days giving a red solution with precipitation of Base.HOTf. 

A highly enantioselective synthesis of (2S)-a-(hydroxymethyl)glutamic acid, a potent metabotropic receptor ligand, has been accomplished via the catalytic Michael addition of /-butyl 2-naphthalen-l-yl-2-oxazoline-4-carboxylate to CH2=CHC02Et, using the phosphazene base (143) and the (.S )-binaphthyl quaternary ammonium salt (144) as the chiral phase-transfer reagent in CH2CI2 at — 60 °C (<97% < < ).174... 

The asymmetric copper-catalyzed aziridination of styrene with /i-toluenesulfonamide, iodosylbenzene, and 2,2-bis[(4d )-/-butyl-l,3-oxazolin-2-yl]propane catalyst (Evans catalyst) provided the aziridine product with an ee comparable with that previously obtained (Scheme 110) <2001JA7707>. 

Aryl-5,5-bis(oxazolin-2-yl)-l,3-dioxanes 169 have been easily prepared in three steps from diethyl bis(hydroxymethyl)malonate, amino alcohols, and aromatic aldehydes. They have been used for the copper-catalyzed asymmetric cyclopropanation of styrene with ethyl diazoacetate in up to 99% ee for the trawx-cyclopropane (maximum transicis ratio = 77/23) <05TA1415>. The same reaction performed on 2,5-dimethyl-2,4-hexadiene with tert-butyl diazoacetate in the presence of copper catalysts bearing ligand 170, prepared from arylglycines, exhibited remarkable enhancement of the rrawx-selectivity (transicis ratio = 87/13), with 96% ee for the trans product <05JOC3292>. 

Jew and Park achieved a highly enantioselective synthesis of (2S)-a-(hydroxy-methyljglutamic acid, a potent metabotropic receptor ligand, through the Michael addition of 2-naphthalen-l-yl-2-oxazoline-4-carboxylic acid tert-butyl ester 72 to ethyl acrylate under phase-transfer conditions [38]. As shown in Scheme 5.36, the use of BEMP as a base at —60 °C with the catalysis of N-spiro chiral quaternary ammonium bromide le appeared to be essential for attaining an excellent selectivity. 

---