Catalytic asymmetric cyclopropanation of alkenes with diazoesters in protic and biphasic media

As a C-2 symmetric hydrophilic chiral ligand, a series of 2,6-bis(oxazolinyl)-pyridines (pyboxs) bearing a hydroxyalkyl group on the oxazoline ring has been synthesized from readily available amino acid derivatives. Catalytic asymmetric intermolecular cyclopropanation of electron rich terminal alkenes with diazoesters in the presence of hydrophilic pybox ligand, pybox-hm and Ru(II) complex proceeded smoothly in protic or biphasic media to give the corresponding cyclopropanation products in 97:3 to 99:1 trans/cis ratios and 90 to 97% ee. In the case of the intramolecular cyclopropanation reaction of trans-cinnamyl diazoester using Ru(II)(pybox-he) complex in biphasic medium gave the corresponding cyclopropane ring fused lactone in 52% ee. Steric tuning of the chiral environment of pybox ligands was simply achieved by using a weak interaction between the solvent and the hydroxyl groups of the chiral ligand. The solubility of the new hydrophilic pybox and Ru(II) complexes in protic solvents is dramatically increased; hence, the efficiency of these catalysts enhanced the rate of cyclopropanation. Furthermore, the active catalyst in the water phase can be re-used several times for the cyclopropanation reaction. (C) 2003 Elsevier Science Ltd. All rights reserved.