DOI:10.1002/adsc.200600623 Electronic and Steric Effects of Atropisomeric Ligands SYNPHOS $ and DIFLUORPHOS $ vs. BINAPs in Rh(I)-Catalyzed Asymmetric Pauson–Khand Reaction Dong Eun Kim, a Choong Choi, a In Su Kim, a SØverine Jeulin, b Virginie Ratovelomanana-Vidal, b, * Jean-Pierre GenÞt, b, * and Nakcheol Jeong a, * a Department of Chemistry, Korea University, Seoul 136-701, Korea Fax:(+ 82)-2-3290-3121; e-mail: njeong@korea.ac.kr b Laboratoire de Synthse SØlective Organique et Produits Naturels Ecole Nationale SupØrieure de Chimie de Paris 11, rue Pierre et Marie Curie, 75231 Paris Cedex 05, France Fax:(+ 33)-1-4407-1062; e-mail: virginie-vidal@enscp.fr or jean-pierre-genet@enscp.fr Received:December4,2006;Revised:June4,2007 Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/. Abstract: The electronic and steric effects of chiral biaryl diphosphine ligands on the Rh(I)-catalyzed asymmetric Pauson–Khand type reaction were exam- ined. We demonstrated that enantioselectivity and reaction yield were influenced by the electronic den- sity on phosphorus, the dihedral angle of ligands and the electronic density of the alkyne substrate. Li- gands bearing a narrower dihedral angle than Binap, such as Synphos (L4) and Difluorphos (L5), were found to increase substantially the enantioselectivity of the reaction, compared to Binap-type ligands. Li- gands having a deshielded phosphine, such as p-CF 3 - Binap (L3) and Difluorphos (L5) provided better enantioselectivity than Binap, with reduced forma- tion of side products, especially with electron-poor alkyne substrates. Keywords: atropisomeric ligands; electronic effects; enantioselectivity; Pauson–Khand reaction; steric ef- fects Introduction In recent years, a great deal of research has been de- voted to the asymmetric catalytic Pauson–Khand re- action (denoted as the PKR hereafter), [1] which is de- fined as the transition metal mediated [2 + 2 + 1] cy- cloaddition of an alkyne, an alkene and CO. [2] Various versions of the enantioselective PK type reaction using cobalt, [3] titanium, [4] rhodium [5] and iridium [6] to- gether with chiral ligands have been published. [3] Sev- eral years ago, we described the first rhodium-cata- lyzed enantioselective PKR under a CO atmosphere in the presence of an atropisomeric ligand (Scheme1). [5] These early results were promising in terms of enantioselectivity, but they also exhibited some limitations with certain classes of substrates. Efforts to optimize this methodology were report- ed, [7] but improvements in terms of enantioselectivity and chemical yield still need to be realized. In a pre- vious paper, [8] we performed a systematic screening of twelve different classical PKR 1,6-enyne substrates and six Binap-type ligands displaying different elec- tronic properties. Accurate interpretation of the re- sults showed a clear tendancy: for a given Binap ligand, the more electron-rich the alkyne, the better the enantioselectivity (but the lower the yield); for a given sustrate, the more electron-poor the Binap ligand, the higher the enantioselectivity (almost no in- fluence on the yield). Especially enantioselectivities obtained with p-CF 3 -Binap ligand, bearing a far lower electronic density on phosphorus than Binap, were 2 to 5% higher than those obtained with Binap, as shownonScheme2. In the present study, we wished to get a deeper in- sight in designing an optimized Rh(I)/ligand catalyst for enantioselective PKR under CO atmosphere, by Scheme1. The Rh(I)-catalyzed asymmetric PKR. Adv. Synth. Catal. 2007, 349,1999–2006 #2007Wiley-VCHVerlagGmbH&Co.KGaA,Weinheim 1999 FULL PAPERS