( S)-Serine derived N–O and N–P oxazoline ligands for asymmetric catalysis

Abstract

( S)-Serine methyl ester and a range of carboxylic acids RCO 2H ( a R=(η 5-C 5H 4)Fe(η 5-C 5Ph 5), b (η 5-C 5H 4)Co(η 4-C 4Ph 4), c (η 5-C 5H 4)Fe(η 5-C 5H 5), d 1-adamantyl, e C 6H 5) were readily transformed in three steps into ( R)-4-hydroxymethyloxazoline N–O ligands 3a– e containing the R substituent at position 2. Two further N–O ligands ( S)-4-(1-hydroxy-1-methylethyl)oxazoline 3f and ( S)-4-(1-hydroxy-1,1-diphenylmethyl)oxazoline 3g both containing (η 5-C 5H 4)Co(η 4-C 4Ph 4) as a 2-substituent were also generated. Use of 5 mol % of 3a– f promoted the synthesis of ( R)-1-phenylpropan-1-ol from benzaldehyde and diethylzinc, 3a resulting in a highest ee of 75%. In a two step synthesis via an intermediate mesylate, 3b was converted into the corresponding ( S)-4-(diphenylphosphinomethyl)oxazoline N–P ligand 19 , and an X-ray crystal structure analysis was obtained of the palladium dichloride adduct. Treatment of 3a– e with Ph 2PCl under basic conditions resulted in the corresponding phosphinite–oxazoline N–P ligands 4a– e . All the N–P ligands were screened to determine the most selective for the palladium-catalysed allylic alkylation with dimethyl malonate of the following racemic substrates: (i) 1,3-diphenylprop-2-enyl acetate [96% ee ( S) with 4e ], (ii) 1,3-dimethylprop-2-enyl pivalate [70% ee ( S) with 4b ] and (iii) 3-cyclohexenyl acetate [48% ee ( R) with 4c ].