Breaking Conjugation: Unusual Regioselectivity with 2-Substituted Allylic Substrates in the Tsuji-Trost Reaction

η -Allyl palladium complexes are key intermediates in Tsuji-Trost allylic substitution reactions. It is well known that (η -1-aryl-3-alkyl substituted allyl)Pd intermediates result in nucleophilic attack at the alkyl substituted terminus. In contrast, the chemistry of (η -1,2,3-trisubstituted allyl)Pd intermediates is relatively unexplored. Herein we probe the regioselectivity with 1,2,3-trisubstituted allylic substrates in Tsuji-Trost allylic substitution reactions. DFT investigation of cationic (η -1-Ph-2-B(pin)-3-alkyl-allyl)Pd(PPh ) intermediates predict that nucleophilic attack should occur preferentially on -allyls rather than the -isomers to generate benzylic substitution products under Curtin-Hammett conditions. Experimentally, systematic studies with 1,2,3-trisubstituted allylic substrates revealed that a Linear Free Energy Relationship (LFER) is observed when Charton steric parameters of the C-2 substituents are plotted against the log of the ratio of regioisomers. Bulkier C-2 substituents in 1,2,3-trisubstituted η -allyl palladium intermediates provide stronger preference for nucleophilic attack at -oriented benzylic termini. Additionally, the geometry of 1,4-elimination products supports the presence of -allyl palladium intermediates.