Asymmetric synthesis of N-substituted N-hydroxyureas

Asymmetric synthesis of (S)-N-(1-arylethyl)-N-hydroxyureas, (S)-N-(6-methoxy)- and (S)-N-(6-benzyloxy-2,3-dihydrobenzofuran-3-yl)-N-hydroxytirea- lipoxygenase inhibitor, is described. Three approaches to the formation of the N-hydroxyurea moiety at the stereogenic center have been used. The first one, via the reaction of (R)-6-benzyloxy-2,3-dihydrobenzofuran-3-ol with N,O-bis(phenoxycarbonyl)hydroxylamine under Mitsunobu conditions, leads to a partially racemized product. Alternatively, the enantioselective reduction of oximes O-benzyl ethers of acetophenone, 4-methoxy- and 4-benzyloxyacetophenone, 6-methoxy- and 6-benzyloxy-2,3-dihydrobenzofuran-3-one with borane/oxazaborolidines can be controlled to produce either the corresponding hydroxylamine O-benzyl ethers or primary amines which have been transformed into N-substituted N-hydroxyureas in 57% to 99% ee. (C) 2008 Elsevier Ltd. All rights reserved.