Novel chiral P,O-ligands for homogeneous Pd(0) catalysed asymmetric allylic alkylation reactions Vanda Raquel Marinho, a Ana Isabel Rodrigues b and Anthony J. Burke a, * a Departamento de Quı ´mica and Centro de Quı ´mica de E ´ vora, Universidade de E ´ vora, Rua Roma ˜o Romalho 59, 7000 E ´ vora, Portugal b Departamento de Tecnologia de Indu ´ strias Quı ´micas, Instituto Nacional de Engenharia, Tecnologia e Inovac ßa ˜o, Estrada do Pac ßo do Lumiar, Edifı ´cio F, 1649-038 Lisboa, Portugal Received 30 November 2007; accepted 17 January 2008 Abstract—Two novel P,O-coordinating chiral phoshine–amide ligands with hydroxymethyl side chains 5a and 5b were prepared and tested in some benchmark Pd(0) catalysed asymmetric allylic alkylations. The conversions and enantioselectivities were generally good, with a highest conversion of 92% and a highest ee of 62% obtained using 1,3-diphenylpropenyl acetate as substrate. A number of pal- ladium pre-catalysts were used, but it was [Pd(allyl)Cl] 2 which gave the best results. Ligand 5b was seen to give better enantioselectivities. Ó 2008 Elsevier Ltd. All rights reserved. 1. Introduction Catalytic asymmetric synthesis has currently considerable application in providing useful enantiomerically pure compounds. One of the outstanding endeavours in the area is the creation of new C–C and C–X bonds. Since 1977, the asymmetric allylic alkylation (AAA) reaction has become a standard approach for achieving this objective. 1,2 Many chiral ligands have been screened for this particular reaction; these generally contain P or N, possess C 2 or C 1 symmetry and can be of a homobidentate type (e.g., diphosphines and bisoxazolines) or of a heterobidentate nature (e.g., phosphinooxazolines). 1 Trost’s ligand 1 (Fig. 1) has shown considerable applicabil- ity for this particular reaction, 2,3 and has elicited much interest from the chemical community. An interesting study of this ligand in Pd(0) catalysed allylic alkylations by Lloyd-Jones and co-workers 4 demonstrated that under certain circumstances, an alternative P,O mode of coordination of this ligand with Pd was possible giving a catalytically active complex (Fig. 1). Amatore et al. 5 have unambiguously shown this type of coordination in a Pd–allyl complex formed with Trost’s diaminocyclohex- ane-2-diphenylphosphinonapthoyl ligand. Clayden et al. 6 developed an atropisomeric phosphinamide that showed excellent enantioselectivities in the benchmark allylic alkyl- ation of 1,3-diphenylpropenyl acetate. Also worthy of note are the phosphine–amide ligands 3 and 4 (Fig. 2) derived from O-methoxy (S)-phenylalaninol developed by Mino et al. 7 that were successfully used in palladium catalysed asymmetric allylic alkylations giving a highest ee of 85%. Sinou and co-workers 8 have also developed a series of sugar-derived amides that have also been successful for this NH HN O O Ph 2 P PPh 2 (R,R)-1 NH HN O O 2 P Ph Ph Pd P Pd Ph Ph 6-membered chelate Figure 1. 0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetasy.2008.01.024 * Corresponding author. Tel.: +351 266745310; fax: +351 266745303; e-mail: ajb@dquim.uevora.pt Available online at www.sciencedirect.com Tetrahedron: Asymmetry 19 (2008) 454–458