P-stereogenic P/N hybrid ligands: a remarkable switch in enantioselectivity in palladium-catalyzed asymmetric allylation q Hiroshi Danjo, Masato Higuchi, Mitsuhiro Yada and Tsuneo Imamoto * Department of Chemistry, Faculty of Science, Chiba University, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan Received 17 September 2003; revised 20 October 2003; accepted 24 October 2003 Abstract—Optically active P-stereogenic phosphine/oxazoline bidentate ligands (1) were prepared and applied to palladium-cata- lyzed allylic substitution of 1,3-diphenyl-1-acetoxy-2-propene with dimethyl malonate. The absolute configuration of the allylation product was remarkably switched by changing a palladium/ligand ratio between 1/1 and 1/2. Ó 2003 Elsevier Ltd. All rights reserved. Many types of optically active ligand have been designed and prepared to develop efficient catalytic asymmetric transformation processes. 1 Among them, the bidentate ligands with two different donor atoms (the so-called Ôhybrid ligandsÕ) are one of the most effective classes, and the catalytic ability of the metal complexes of these ligands has recently been well doc- umented. 2 One advantage of this type of ligand lies in the difference in trans influence between two donor atoms. 3 Furthermore, the coordination ability of the donor atoms may affect reactivity and stereoselectivity in catalytic processes. Previously, we demonstrated that P-stereogenic bis(tri- alkylphosphine) ligands (abbreviated to BisP* and MiniPHOS) were effective in rhodium-catalyzed asym- metric hydrogenation of various enamides. 4 The P-ste- reogenic trialkylphosphine unit constructs an asymmet- ric environment very close to the rhodium center, and consequently exhibits high enantioselectivity. Moreover, oxidative addition of the rhodium to hydrogen is accel- erated due to high electron density at the donor atom. To display the extended utility of these P-stereogenic phosphine ligands, we report herein the preparation of the phosphine/oxazolines with two chirogenic centers both at the phosphorus atom and the oxazoline ring as a new class of P/N hybrid ligands 1, and their use in palladium-catalyzed asymmetric allylic substitution (Scheme 1). We anticipated that the cooperation of the two stereogenic centers would lead to characteristic reactivity and selectivity in catalytic asymmetric reac- tions. Phosphine/oxazoline ligands 1 were prepared from P- stereogenic boranatophosphinoacetic acid 2 via inter- mediates 3 and 4 according to the reported procedure (Scheme 1). 5;6 Non-P-stereogenic phosphine/oxazoline ligand 1c was prepared in a similar manner. 7 P R 1 R 2 BH 3 OH O P R 1 R 2 BH 3 N H O OH R 4 R 3 P O N P O N t-Bu Me H t-Bu Me i Pr c-Hex c-Hex H t-Bu Me Me H Me BH 3 R 1 R 2 R 1 R 2 R 3 R 4 R 3 R 4 2 3 4 1 a) b) c) 1b 1c 1d i Pr i Pr 1a R 2 R 3 R 4 R 1 t-Bu Me H 1-Ad Me H t-Bu t-Bu 1e 1f R 2 R 3 R 4 R 1 Ph Me H Fc Me H t-Bu t-Bu 1g 1h Scheme 1. Preparation of optically active P/N hybrid ligands 1. Reagents and conditions: (a) amino alcohol, EDCI, HOBt, DMF, rt; (b) MsCl, Et 3 N, CH 2 Cl 2 , rt; (c) 1: HBF 4 ÆOMe 2 , )10 °C to rt, 2: aq NaHCO 3 , rt. EDCI ¼ N-(3-dimethylaminopropyl)-N 0 -ethylcarbo- diimide hydrochloride, HOBt ¼ 1-hydroxybenzotriazole, MsCl ¼ meth- anesulfonyl chloride, 1-Ad ¼ 1-adamantyl, Fc ¼ ferrocenyl. Keywords: Palladium; Asymmetric allylic substitution; P-stereogenic phosphine; P/N hybrid ligand. q Supplementary data associated with this article can be found at doi:10.1016/j.tetlet.2003.10.160 * Corresponding author. Tel./fax: +81-43-290-2791; e-mail: imam- oto@faculty.chiba-u.jp 0040-4039/$ - see front matter Ó 2003 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2003.10.160 Tetrahedron Letters 45 (2004) 603–606 Tetrahedron Letters