Hammett 13 CNMRandX-raystudiesof p-allylpalladium phosphinooxazolinechiralligandcomplexes Paul B. Armstrong, a Lisa M. Bennett, b Ryan N. Constantine, a Jessica L. Fields, a Jerry P. Jasinski, b Richard J. Staples c and Richard C. Bunt a, * a Department of Chemistry and Biochemistry, Middlebury College, Middlebury, VT 05753, USA b Department of Chemistry, Keene State College, Keene, NH 03435, USA c X-ray Crystallography Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA Received 16 August 2004; revised 7 January 2005; accepted 10 January 2005 Available online 23 January 2005 Abstract—The transmission of substituent effects across the palladium center to the allyl carbons is monitored by 13 C NMR and X-ray crystallography as a way to probe electronic asymmetry in chiral ligand design. Based on their similar chemical shift trends and X-ray structures, the p-allylpalladium intermediates provide a good model for early transition state reactions, which are less sensitive to electronic perturbations. Hammett analysis supports an electronic basis for enantioselection that increases as the tran- sition state becomes later. Ó 2005 Elsevier Ltd. All rights reserved. Phosphinooxazoline (PHOX) chiral ligands have proven extremely effective at inducing asymmetry in palladium- catalyzed allylic-substitution reactions. 1 These ligands are proposed to function by controlling the ratio of the exo to endo p-allylpalladium intermediates and then directing nucleophilic addition trans to phosphorus (the better acceptor ligand) in the favored exo intermediate. The low-temperature NMR structure of the initially formed alkene–palladium complex has established this Ôtrans to phosphorus in exoÕ addition as the major path- way. 2 Nonetheless, this does not preclude other explana- tions for its favorability (e.g., steric interactions with the nucleophile or in the product alkene complex) nor does it provide any information about the pathway(s) leading to the minor enantiomer. Our Hammett studies of the enantioselectivity with elec- tronically modified PHOX ligands (1a–f) provided addi- tional support for the electronic basis of the trans to phosphorus addition mechanism, but they also demon- strate that the nucleophile plays an important role in determining the enantioselectivity. 3 In particular, for reactions with sodiodimethyl malonate as the nucleo- phile the eeÕs were less sensitive to the backbone substi- tuent (X) (1a–f: 89–93% ee). In contrast, for reactions with benzylamine as the nucleophile the eeÕs showed a great sensitivity to the backbone substituent (X) (1a–f: 16–67% ee). These results suggest that the position of the transition state also influences the enantioselectivity. To gain further insight into the basis for enantioselecti- vity and the position of the transition state, we measured the 13 C NMR chemical shifts and examined several X-ray structures of the p-allylpalladium intermediates themselves (2a–f), which are regarded as good models for an early transition state structure. 4 13 C NMR chemi- cal shifts have been successfully correlated to both positive charge density 5 and regioselectivity of nucleophilic attack with substituted 1,3-diphenylallyl- palladium complexes with achiral ligands by Hammett analysis. 6 In the case of ligands 1a–f the electron donat- ing or withdrawing substituent is on the ligand back- bone and should show Hammett correlations via electronic transmission across the palladium center to the allyl termini. Based on the proposed mechanism for enantioselection, the biggest effect was expected on C 3 in the exo diastereomer. Palladium complexes 2a–f were prepared from the corre- sponding chiral ligands (1a–f) 3 and 1,3-diphenylallylpal- ladium chloride dimer by reaction with silver tetrafluoroborate in acetone (Scheme 1). 6b,7 The com- plexes were obtained in essentially quantitative yield 0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2005.01.032 Keywords: Asymmetric catalysis; Hammett analysis; N,P-ligands; Palladium; p-Allyl complexes. * Corresponding author. Tel.: +1 802 443 2559; fax: +1 802 443 2072; e-mail: rbunt@middlebury.edu Tetrahedron Letters 46 (2005) 1441–1445 Tetrahedron Letters