A new chiral ruthenium complex for catalytic asymmetric cyclopropanation

A new chiral ruthenium complex 6, featured with an N,O-mixed polydentate ligand, was synthesized and characterized. This ruthenium complex showed high efficiency in catalytic cyclopropanations of alkenes with diazoacetates. High trans/cis selectivity and enantioselectivity (up to 96%) were achieved with the readily accessible ethyl diazoacetate as the reagent. © 2002 Elsevier Science Ltd. All rights reserved. Metal-catalyzed asymmetric cyclopropanation remains of great interest due to its versatile applications in synthetic organic chemistry. Although several excellent metal catalysts such as Cu-salicylaldimine, Cu-semicorrin, Cu-bisoxazoline, and chiral dirhodium system, have been developed for asymmetric intermolecular or intramolecular cyclopropanations, the development of new catalysts in terms of low catalyst loading, high diastereoselectivity, good enantioselectivity, and the use of readily accessible and cheap diazo compounds, remains an important goal. Several successful chiral Ru catalysts have also been developed for intermolecular cyclopropanation of olefins and diazoacetates. Among them are Nishiyama’s Ru Pybox system, Katsuki’s Ru salen system, and Scott’s Ru Schiff-base complex. Herein we wish to report a novel and efficient chiral ruthenium catalyst 6 for intermolecular cyclopropanation of olefins with diazoacetates. Low catalyst loading (1 mol%), good trans/ cis selectivity (90/10), and high enantioselectivities (up to 96%) have been achieved with the readily available ethyl diazoacetate as the reagent. Possible interaction between the esters of carbenes and the hydroxyl groups in 6 is a novel feature of our catalytic system. In the course of exploring ligands with a well-defined chiral environment, we designed an N,O-mixed polydentate ligand 3. This ligand can be directly prepared from chiral 2-amino-2 -hydroxy-1,1 -binaphthyl 1 (NOBIN) and 2,6-pyridinedimethanal 2 (Scheme 1). By refluxing the mixture of 1 and 2 in i-propanol in the presence of 4 A molecular sieves, ligand 3 was obtained in 75% yield with a high purity (>95%). We hoped to make ruthenium complex 4 through the reaction of [RuCl2(p-cymene)]2, pyridine, and ligand 3 in ipropanol. However, our results showed that a different air-stable Ru complex 5 was formed. The structure of 5 was characterized by NMR and MS analysis, and its naphthol protons were also examined by H-D exchange. We envisioned that the scaffold of 5 might be good for catalytic cyclopropanation reaction. However, 5 showed no reactivity for cyclopropanation of styrene and ethyl diazoacetate at room temperature. In order to make an active Ru catalyst for cyclopropanation, we employed bulkier pyridine derivatives for the preparation of Ru catalysts. Surprisingly, when we used 2,6-dichloropyridine or 2-chloropyridine as the base and methanol as the solvent, a purple precipitate was formed (Scheme 2). This precipitate was identified to have no pyridine moiety according to its H NMR spectrum, while one mol equivalent of methanol was observed. We thus assumed that the structure of the precipitate was a methanol-coordinated Ru complex 6. To further corroborate the assignment, 6 was treated with pyridine in dichloromethane solution, leading to the formation of Ru complex 5. It is noteworthy that 2,6-dichloropyridine or 2-chloropyridine did not exchange with the coordinated methanol of 6 in the reaction to form pyridine coordinated Ru complex like 5. We consider that this could be attributed to the steric effect of the substituted pyridines. The steric bulk of the ligand 3 might only allow the coordination of unhindered pyridine to the ruthenium atom. Complex 6 is stable under N2 atmosphere and can be stored for a long time. No sign of decomposition was observed according to its NMR after it was stored under N2 for 6 months. * Corresponding author. Tel.: 1-814-863-5614; fax: +1-814-863-8403; e-mail: [email protected] 0040-4039/02/$ see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII: S0040 -4039 (02 )00317 -9