A novel procedure for the preparation of enantiopure 1,4-disubstituted 2-imidazolines is reported. Enantiopure beta-amino alcohols are converted into N-hydroxyethylamides, which are reacted with excess thionyl chloride, or with thionyl chloride followed by phosphorus pentachloride to yield N-chloroethylimidoyl chlorides. These intermediates are treated with amines and anilines to produce N-chloroethylamidines, which are converted into imidazolines upon workup with aqueous hydroxide. The method is simple and efficient and has been used to prepare a wide variety of enantiopure imidazolines, in a modular fashion, from readily available amino alcohols.

A convenient new method for the preparation of 2,2'-biimidazolines is reported. Amino alcohols were reacted with dimethyl oxalate, and the product hydroxy amides converted into chloroamides by reaction with thionyl chloride. Treatment with PCl5, followed by diamines (ethanediamine, propane-1,3-diamine, 2,2-dimethylpropane-1,3-diamine) furnished a series of enantiopure tricyclic biimidazolines. Complexes of two of the ligands with PdCl2 were prepared and their X-ray crystal structures were determined. The biimidazolines were tested as ligands for asymmetric Pd-catalysed allylations. Moderate enantioselectivity (up to 80% ee) was found for the reaction of dimethyl malonate with diphenylallyl acetate, with the 5,7,5 fused tricyclic systems outperforming the 5,6,5 analogues. The corresponding reaction of pentenyl acetate gave lower enantioselectivity (44-57% ee), and proved very sensitive to the donor strength of the ligands, the stronger donors giving lower yields. The results provide a further demonstration of the value of the 'tunability' of imidazoline ligands.

A series of ansa-quinones has been prepared by chemical synthesis, and evaluated by biological techniques. Thus, 19-membered ansa-lactams, simplified analogues of the naturally occurring Hsp90 molecular chaperone inhibitor geldanamycin, were obtained by concise routes, the key steps being the combination of a ring-closing metathesis to give a 17-membered ring followed by Claisen rearrangement to effect ring expansion. The methodology was also used to prepare an "unnatural" 18-membered ring analogue. In ATPase enzyme assays, the synthetic ansa-quinones were weak inhibitors of Hsp90.

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