A practicable synthesis of enantiopure 2-aminomethyl-1-bromo- and 2-aminomethyl-1-iodoferrocenes

Enantiopure 2-aminomethyl-1-bromo- and 2-aminomethyl-1-iodoferrocenes as well as 1-bromo- and 1-iodo-2-(dimethylaminomethyl)ferrocenes were obtained via three routes: (i,ii) chromatographic separation of diastereomers, prepared from racemic N-(1-bromo- or 1-iodoferrocenylmeth-2-yl)-N,N,N-trimeth lammonium iodide with either (S)-phenylethylamine or (1R,2S)ephedrine, followed by quaternization with methyl iodide and reaction with either aqueous ammonia or aqueous dimethylamine; and (iii) diastereoselective lithiation of (R)-N-ferrocenylmethyl-2-methoxymethylpyrrolidine (98% de) and quenching with iodine, followed by quaternization of the amine intermediate with methyl iodide and reaction with either aqueous ammonia or aqueous dimethylamine. The absolute configuration of all products and intermediates was determined via chemical correlation and CD spectroscopy. The assignment was confirmed by an X-ray structure analysis of (1R,2S,S-p)-N-(1-hydroxy-1-phenylprop-2-yl)-N-2-iodoferrocenylmethyl-N,N-dimethylammonium iodide.