AgOAc catalyzed asymmetric [3+2] cycloaddition of azomethine ylides with chiral ferrocene derived P,S ligands

Ferrocene derived P,S-heterodonor ligands were effectively used in AgOAc catalyzed asymmetric cycloaddition of azomethine ylides. The roles of planar chirality and electronic properties of the phosphorous substituents have been examined, and up to 93% ee was obtained. 2007 Elsevier Ltd. All rights reserved. The 1,3-dipolar cycloaddition reaction has become a powerful synthetic tool, providing access to highly functionalized O-, Sand N-containing heterocycles. The [3+2] cycloaddition of azomethine ylide 1,3-dipoles with olefinic dipolarophiles constitutes a powerful and reliable approach to the synthesis of highly substituted pyrrolidine derivatives, which are important building units in organic synthesis and can be used as organic catalysts in many asymmetric transformations. In early research, stereoselectivity in the 1,3-dipolar cycloaddition of azomethine ylides was achieved in the presence of a stoichiometric amount of chiral Lewis acid or a chiral auxiliary. The methodology of using a catalytic amount of chiral Lewis acid might be more desirable and has been well developed recently. A variety of Lewis acids such as Ag(I), Cu(I), Cu(II) and Zn(II) have proved to be excellent catalytic precursors. Fesulphos ligands, P,S ligands only with planar chirality developed by Carretero’s group, were successfully used in the Cu(I) catalyzed cycloaddition of azomethine ylides, and excellent results were obtained when N-phenylmaleimide was used as dipolarophile. However, bad endo/exo selectivity was achieved when the dipolarophile was changed to dimethyl maleate. Our group has explored bifunctional AgOAc catalyzed 1,3-dipolar cycloaddition of azomethine ylides with ferrocenyloxazoline derived chiral P,N ligands, and up to 98% ee was obtained. Intrigued by the effectiveness of P,S-heterdonor ligands in asymmetric reactions, we decided to explore the application of ferrocene derived P,S ligands 0040-4039/$ see front matter 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2007.04.101 * Corresponding author. Tel./fax: +86 411 84379220; e-mail: [email protected] in AgOAc catalyzed asymmetric [3+2] cycloaddition of azomethine ylides. The roles of planar chirality and electronic properties of the phosphorous substituents were also studied. The chiral P,S ligands (1a–d and 2) can be easily prepared according to known methods. Ligands 1a–d were previously synthesized by our group and used in the asymmetric hydrogenation of quinolines. In the asymmetric cycloaddition, our initial study showed that AgOAc/1a effectively catalyzed the cycloaddition of 5a with N-phenylmaleimide, and 6a was obtained within 2 h with only endo selectivity and good enantioselectivity (Table 1, entry 1). The ligand 2 has the same central chirality and opposite planar chirality compared to 1a. The opposite absolute configuration and lower enantioselectivity were obtained when 2 was used (entry 2). The lower ee may be caused by the mismatched nature of (S) planar chirality with the (S) central chirality. Next, the effect of the substituent R in ligands 1b–d was studied in order to obtain better enantioselectivity. When R is an electron-withdrawing group, the ee decreased to 82% (entry 3). On the other hand, the ee can be enhanced slightly when R is an electron-donating group (entry 4–5). The cycloaddition was also studied in different solvents. Complete conversion was observed within 2 h in Et2O, THF, CH2Cl2 and toluene. The highest ee was obtained in Et2O. Further improvements in enantioselectivity were made through the variation of the electronic properties of the phosphorous substituents in ligand 1c. As Table 1. AgOAc catalyzed asymmetric cycloaddition of 5a with N-phenylmaleimide