Asymmetric synthesis of N-1-(heteroaryl)ethyl-N-hydroxyureas

The asymmetric synthesis of two 5-lipoxygenase inhibitors (R)-N-1-(benzofuran-2-yl)ethyl-N-hydroxyurea, 99% ee, and (R)-N-1-(benzo[b]thiophen-2-yl)ethyl-N-hydroxyurea, 95% ee, is described. The enantioselective reduction of 1-(benzofuran-2-yl)ethanone oxime O-benzyl ether and 1-(benzo[b]thiophen-2-yl)ethanone oxime O-benzyl ether with borane oxazaborolidine, generated from (1R,2S,3R,4S)-3-amino-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol, was used for the formation of the stereogenic centres.

Figure optionsDownload as PowerPoint slide

(R)-(+)-N-(1-(Benzofuran-2-yl)ethyl)-O-benzylhydroxylamineC17H17NO2Ee = 92%[α]D20=+46.6 (c 1.77, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R), chemical correlation

(R)-(+)-N-1-(Benzofuran-2-yl)ethyl-N-hydroxyureaC11H12N2O3Ee = 99%[α]D20=+14.4 (c 0.42, DMSO)Source of chirality: asymmetric synthesisAbsolute configuration: (R), chemical correlation