Camphane-based aminophosphine ligands for Pd-catalyzed asymmetric allylic alkylation Irena Philipova a , Georgi Stavrakov b , Vladimir Dimitrov a,⇑ a Institute of Organic Chemistry with Center of Phytochemistry, Bulgarian Academy of Science, Acad. G. Bonchev 9, Sofia 1113, Bulgaria b Faculty of Pharmacy, Medical University of Sofia, Str. Dunav 2, Sofia 1000, Bulgaria article info Article history: Received 22 July 2013 Accepted 3 September 2013 Available online 7 October 2013 abstract A practical synthesis of new chiral aminophosphine ligands based on the camphane scaffold bearing alk- oxy groups was accomplished. The application of these ligands in the Pd-catalyzed allylic alkylation of (E)-1,3-diphenyl-2-propenyl acetate proceeded with excellent conversions and ee’s of up to 91%. Varia- tion of the alkoxy substituents did not substantially influence the catalytic performance. Ó 2013 Elsevier Ltd. All rights reserved. 1. Introduction Chiral bidentate chelates containing phosphorus and an addi- tional donor atom possessing different electronic properties have proven to be highly effective ligands in a variety of transition- metal-catalyzed asymmetric reactions. 1 Such a type of heterobid- entate system induces asymmetry in a reaction not just through steric factors, but also by generating electronic asymmetry on the metal center through the presence of different coordinating donor atoms. 2 The most important and widely used of these unsymmet- rical chiral ligands are those which bear nitrogen and phosphorus functional moieties, the P,N-ligands. 2,3 The majority of the exam- ples utilize an sp 2 nitrogen. Ligands possessing an sp 3 nitrogen do- nor atom have rarely been studied. 4 From among the numerous naturally occurring monoterpe- noids, camphor derived structures are of particular importance. This is largely due to the fact that camphor is readily available and undergoes a wide variety of transformations, and still remains attractive as an inexpensive source of enantiopure building blocks. 5 Camphor-derived ligands have gained considerable atten- tion due to their rigid and bulky chiral scaffold. 6 Recently, we have accomplished a practical synthesis of camphane based planar chi- ral phosphino-ferrocenecarboxamide I (Fig. 1) and phosphino- benzencarboxamide ligands II (Fig. 1). 7 The latter were effectively modified both on the amide moiety and the phosphine atom, thus enabling fine tuning of their coordination properties. The applica- tion of these ligands in the Pd-catalyzed asymmetric allylic alkyl- ation (AAA) as P,O-chelates proceeded with a promising degree of enantioselectivity (up to 92%). 7c The use of a camphane based chiral auxiliary proved to be the major contributor to the asym- metric induction in the catalytic process. Encouraged by these observations, we expanded the approach to the synthesis of ami- nophosphine analogs of the phosphino-carboxamide ligands III (Fig. 1). Thus, we have the opportunity to investigate the effect of different donor heteroatom pairs on the reactivity of the transition metal complexes and asymmetric induction in the catalytic pro- cess. Herein we report a practical synthesis of new chiral amino- phosphine ligands on the base of the camphane scaffold and their application in Pd-catalyzed asymmetric allylic alkylations. Variation of the substituents of the ether moiety of the bicyclic 0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tetasy.2013.09.003 ⇑ Corresponding author. Tel.: +359 2 9606157; fax: +359 2 8700225. E-mail address: vdim@orgchm.bas.bg (V. Dimitrov). Fe PPh 2 N O O N O R PPh 2 I III N O O PPh 2 II Figure 1. Tetrahedron: Asymmetry 24 (2013) 1253–1256 Contents lists available at ScienceDirect Tetrahedron: Asymmetry journal homepage: www.elsevier.com/locate/tetasy