Email Discussion: Poster 35 (Dr. Orera) Pedro Merino
Email Discussion: Re: Poster 35 (Prof. Orena) orena@anvax1.cineca.it
Email Discussion: http://www.ch.ic.ac.uk/papers/orena Yannick LANDAIS
Email Discussion: re: Landais query for poster 35 (Orena) orena@anvax1.cineca.it

In order to obtain either 1a or 1b, the amide 2, containing the (S)-phenylethylamine as the chiral auxiliary, has been cyclised with Mn(OAc)3-Cu(OAc)2. A diastereomeric mixture (d.r. 70:30) of pyrrolidin-2-ones 3a and 3b is obtained in 53% yield. After silica gel chromatography, pure 3a and 3b are isolated and the configurations are assigned on the basis of ¹H NMR spectra and confirmed by n.O.e. experiments. The moderate distereoselection can be explained through molecular mechanics calculations.

The major isomer 3a is readily converted into the 4-ethenylpyrrolidin-2-one (4a) in 75% yield by treatment with NaCl in wet DMF for 2 h. This compound undergoes ozonization in dichloromethane at -78 °C to give the aldehyde 5a in 78% yield. No trace of epimerization at C-4 is evidenced by 1H NMR spectrum. By oxidation with Jones' reagent at 0 °C the aldehyde 5a is converted into the corresponding carboxylic acid which, after treatment with diazomethane in methanol, affords the methyl ester 6a in 68% yield. The amidic carbonyl is removed by reaction with borane-dimethylsulphide in THF at 45 °C and the aminoester 7a is recovered in 75% yield after silica gel chromatography. The benzylic group at nitrogen is removed by catalytic hydrogenation on Pd-C 10% in methanol. The solvent containing the ester 8a is evaporated and the residue is placed into a column fitted with Amberlyst IRA 400 in the OH- form. After elution with acetic acid pure 1a is obtained in 65% yield as a white solid. m.p. 187-188 °C (lit. 188-190 °C); [alpha]D +18.0 (c 1, H2O) [lit. + 18.8 (c 3.1, H2O)]

It is worth mentioning that, starting from the pyrrolidin-2-one 3b, (R)-3-pyrrolidinecarboxylic acid 1b can be obtained in the same way and comparable yield.