Effect of the Leaving Group on the Rate and Mechanism of the Palladium‐Catalyzed Isomerization of Cyclic Allylic Benzoates in Allylic Substitutions

In chloroform, the reaction of cis ‐5‐phenylcyclohex‐2‐enyl 4‐Z‐benzoate ( cis ‐ 1 Z , Z = NO 2 , Cl, H, Me, MeO) with Pd 0 complexes ligated to PPh 3 is reversible and proceeds with isomerization at the allylic position. The rate of isomerization of cis ‐ 1 Z to trans ‐ 1 Z depends on the catalytic precursor: Pd 0 (PPh 3 ) 4 > {Pd 0 (dba) 2 + 2PPh 3 } in agreement with an S N 2 mechanism in the rate‐determining isomerization of the cationic (η 3 ‐allyl)palladium complexes formed in the oxidative addition. For a given precursor, the rate of isomerization of cis ‐ 1 Z to trans ‐ 1 Z also depends on the substituent Z, i.e., on the leaving group. The isomerization rate follows the same order as the leaving group properties: 4‐NO 2 –C 6 H 4 ‐CO 2 – > 4‐Cl–C 6 H 4 ‐CO 2 – > C 6 H 5 ‐CO 2 – > 4‐Me–C 6 H 4 ‐CO 2 – > 4‐MeO–C 6 H 4 ‐CO 2 – . The same tendency is found for the equilibrium constant between the neutral cis ‐ 1 Z and the cationic (η 3 ‐allyl)palladium complex in DMF. The higher the concentration of the cationic (η 3 ‐allyl)palladium complex, the faster the isomerization of cis ‐ 1 Z to trans ‐ 1 Z is. The isomerization of cis ‐ 1 Z to trans ‐ 1 Z and that of the cationic (η 3 ‐allyl)palladium complexes are at the origin of the lack of stereospecificity observed in catalytic nucleophilic allylic substitutions. These isomerizations are affected by both the leaving groups and the Pd 0 precursors, which therefore are not “innocent” but may play an important role in palladium‐catalyzed nucleophilic substitutions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)