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Synthesis of chiral 3‐substituted‐3‐aminomethyl‐pyrrolidines and related compounds
Author(s) -
Suto Mark J.,
Turner William R.,
Kampf Jeffrey W.
Publication year - 1992
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570290612
Subject(s) - chemistry , enantiomer , pyrrolidine , ketone , pyrrolidinones , nitrogen , chiral derivatizing agent , protecting group , organic chemistry , stereochemistry , chiral column chromatography , alkyl
The preparation of a series of chiral 3‐methyl‐3‐substituted‐pyrrolidines/pyrrolidinones starting from ( R )‐4‐(methoxycarbonyl)‐1‐(1 R ‐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.