Optically active imidazoles derived from enantiomerically pure trans-1,2-diaminocyclohexane

A new exploration of monoprotected derivatives of trans-1,2-diaminocyclohexane as a platform for the synthesis of enantiomerically pure imidazole derivatives is described. The primary amino group (-NH2), present in the mono-imine derivative of salicylic aldehyde (hemi-salen derivative) 5 was used for sequential reactions with formaldehyde and the corresponding alpha-(hydroxyimino)ketone. (S)-(-)-1-Phenylethylamine was also used as starting material for the preparation of new imidazole N-oxides 7c and 10a-c, bearing a chiral N-(1-phenylethyl)carboxamido function at C(4). Imidazole N-oxides 10a,b possessing either a Me or i-Pr group at N(1), respectively, follow the known sulfur-transfer pathway to afford the corresponding imidazole-2-thiones 13a,b. However, in the case of imidazole N-oxide 10c with a bulky adamantan-1-yl substituent at N(1), the attempted 'sulfur-transfer reaction' led to the deoxygenated imidazole derivative 14. Finally, the same reaction with 7c, which bears an electron-withdrawing N-(1-phenylethyl)carboxamide residue at C(4) of the imidazole ring, yielded a mixture of deoxygenated imidazole 16 and imidazole-2-thione 15c. (C) 2011 Elsevier Ltd. All rights reserved.