| Abstract: | The preparation of a series of chiral 3-methyl-3-substituted-pyrrolidines/pyrrolidinones starting from (R)-4-(methoxycarbonyl)-1-(1R-phenethyl)-2-pyrrolidinone ( 1 ) is described. The chiral α-methylbenzyl functionality serves not only as a nitrogen protecting group for the pyrrolidine nitrogen, but also as a chiral auxillary. The synthesis of the 4-position enantiomers was accomplished by converting the ester of 1 to the ketone, protecting the ketone as the benzyloxime and separation by chromatography. These key intermediates were converted to the (R) and (S)-3-methyl-3-aminomethylpyrrolidines by removal of the benzyl group followed by oxidation. The 3-methyl-3-(1-aminoethyl)pyrrolidines were obtained via a two step reduction of the corresponding oximes. The stereochemical assignments were determined by X-ray crystallography. |
