1688 Organometallics zyxwvu 1995, zyxwvu 14, 1688-1693 Conformations of zyxw (q3-Cyclohexenyl)palladium Systems. A Molecular Mechanics (MM2) Study Bjorn Bikermark” and Johan D. Oslob Department of Chemistry, Organic Chemistry, Royal Institute of Technology, S-100 44 Stockholm, Sweden Per-Ola Norrby” Department of Medicinal Chemistry, Royal Danish School zyxwv of Pharmacy, Universitetsparken 2, DK-2100 Copenhagen, Denmark Received November 29, 1994@ The primary products from palladium(I1)-assisted nucleophilic addition to 1,4-cyclohexa- dienes ((y3-cyclohexenyl)palladium complexes) have been investigated by molecular mechan- ics (MM2). The observed coupling constants can best be explained by a rapid equilibrium between chair- and boatlike conformations. Methods to estimate the relative amounts of the boat and chair conformations of the complexes are presented. Palladium allyl complexes have been found to be very versatile and important reagents in organic i3ynthesis.l Several palladium-catalyzed conversions of unsaturated substrates proceed via y3-allyl complexes. Included in the range of reactions available are functionalizations of cyclohexenes, l,&cyclohexadienes,and l,4-cyclohexa- dienes, as well as acyclic 1,4- to 1,7-diene~.~ In the palladium-catalyzed nucleophilic displacement of allylic acetates, another facile reaction with (y3-allyl)palladium intermediates, optically active products can be obtained by introduction of chiral ligand^.^^^ In most cases, (y3-allyl)palladium complexes will react with nucleophiles to form allylic products. We have previously studied ways to control the configuration of the product double bond and the regioselectivity of the nucleophilic a tta~k.~ Complications arise from the fast dynamic equilibria in the y3-allyl moiety,6 the rates of which, depending on reaction conditions, are often comparable to the rate of nucleophilic a t t a ~ k . ~ The selectivities in these reactions are determined by the energies and reactivities of the different isomers of the intermediate y3-allyl. In order to rationalize some of these effects, we have recently created a molecular mechanics (MM2) force field for the (y3-ally1)palladium moiety.8 The conformational preferences of the q3-allyl intermediates are especially important for rationaliza- tion and prediction of enantioselectivity in the reaction. @ Abstract published in Advance ACS Abstracts, March 1, 1995. (1) Trost, B. M.; Verhoeven, T. R. In Comprehensive Organometallic Chemistry; Wilkinson, G., Ed.; Pergamon: Oxford, U.K., 1982; Vol. 8, pp 80’2-853. (2)(a) Backvall, J.-E. Acc. Chem. Res. 1983, 16, 335-342. (b) Larock R. C.; Takagi, K. J. Org. Chem. 1984,49,2701-2705. (c) Hall, S. S.; h e r m a r k , B. Organometallics 1984,3, 1745-1748. (3) (a) Godleski, S. A. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, U.K., 1991; Vol. 4, Chapter 3.3, pp 585-661. (b) Harrington, J. P. Transition Metals in Total Synthesis; Wiley: New York, 1990. (4) Peiia-Cabrera, E.; Norrby, P.-0.; Sjogren, M.; Vitagliano, A.; deFelice, V.; Oslob, J.; hermark, B.; Helquist, P., manuscript in preparation. (5) Sjogren, M.; Hansson, S.; Norrby, P.-0.; hermark, B.; Cucciolito, M. E.; Vitagliano, A. Organometallics 1992, 11, 3954-3964. (6) Hansson, S.; Norrby, P.-0.; Sjogren, M. P. T.; hermark, B.; Cucciolito, M. E.; Giordano, F.; Vitagliano, A. Organometallics 1993, 12, 4940-4948 and references cited therein. (7) Sjogren, M. Ph.D. Thesis, The Royal Institute of Technology, Stockholm, Sweden, 1993. In order to elucidate these effects, it is advantageous to study systems where the above-mentioned complica- tions arising from the fast isomerizations in the system (e.g., the y3-y1-y3 isomerization) are absent. This is true in, for example, the y3-cyclohexenylmoiety, where the position of the side groups are locked by the ring. We have recently observed enantioselectivity in the palladium-catalyzed nucleophilic substitution of unsub- stituted cyclohexenyl acetate in the presence of a chiral liga~~d.~J The enantioselectivity here clearly arises from a conformationally induced reactivity difference between the allyl termini in the (y3-cyclohexenyl)palladium ~omplex.~ It is therefore very important to us to be able to correctly describe the conformations of the (y3- cyclohexeny1)palladium complexes. It has also been reported that the conformation of (y3-cyclohexenyl)- palladium complexes governs the mode of attack by acetate.9 (y3-Cyclohexenyl)palladium complexes (e.g. 1) are intermediates in a palladium-assisted functionalization of 1,4cyclohexadieneswhich we reported earlier (Scheme 1).2cJo In the course of this investigation,2cJ0 a large number of (y3-cyclohexenyl)palladium complexes were isolated and characterized. The conformation of these complexes was unclear but was assigned as overall “pseudochair” or “pseudoboat” from the vicinal couplings between allyl and ring methylene protons. However, in most cases the supposed diaxial couplings between ring methylene protons (H5 to H4 and H6) were suspi- ciously low. The numbering of the protons in the cyclohexenyl system is shown in the figure in the lower right corner of Chart 1. For example, in the prototypical compound 1, the couplings J41,52 and J42,52 were 7.8 and 5.7 Hz, respectively (Table 1). These values are in reasonable agreement with a previously observed pal- ladium cyclohexenyl species in a chair conf~rmation,~ (8)(a) Norrby, P.-0.; hermark, B.; Haeffner, F.; Hansson, S.; Blomberg, M. zyxwvu J. Am. Chem. SOC. 1993,115, 4859-4867. (b) Norrby, P.-0. Ph.D. Thesis, The Royal Institute of Technology, Stockholm, Sweden, 1992. (9) Grennberg, H.; Langer, V.; Backvall, J.-E. J. Chem. SOC., Chem. Commun. 1991,- 1190- 1192. (10) (a) Siiderberg, B. C.; h e r m a r k , B.; Hall, S. S. J. Org. Chem. 1988, 53, 2925-2937. (b) Soderberg, B. C. Ph.D. Thesis, Royal Institute of Technology, Stockholm, Sweden, 1987. 0276-7333/95/2314-1688$09.00/0 0 1995 American Chemical Society