Novel stereoselective synthesis of 1,2,3-trisubstituted azetidines

A novel, superbase induced diastereoselective transformation of benzylamino groups containing oxiranes has provided a series of trans-1,2,3-trisubstituted azetidines in good yields. The reaction of the corresponding optically active cis-2,3-disubstituted oxirane yielded the azetidine derivative as a single enantiomer. The structures of the new azetidines were confirmed by NMR spectroscopic methods and, in one case, by single crystal diffraction measurements.

Figure optionsDownload as PowerPoint slide

(+)-(2R,3S)-2-Tosyloxymethyl-3-trityloxymethyloxiraneC30H28O5ee 98.9% (HPLC)[α]D25=-23.8 (c 1.6, CHCl3)Source of chirality: tosylation of the optically active alcoholAbsolute configuration: (2R,3S)

(+)-(2R,3S)-N-Benzyl-N-methyl-2-aminomethyl-3-(trityloxymethyl)oxiraneC31H31NO2ee 98.9% (HPLC)[α]D25=+10.0 (c 1.4, CHCl3)Source of chirality: alkylation of N-methylbenzylamine with optically active tosylateAbsolute configuration: (2R,3S)

(+)-(1′R,2R,3R)-3-(1-Hydroxy-2-trityloxyethyl)-2-phenyl-1-methylazetidineC31H31NO2ee 98.9% (HPLC)[α]D25=+59.8 (c 3.1, CHCl3)Source of chirality: diastereoselective reactionAbsolute configuration: (1′R,2R,3R)