Palladium(II)-Catalyzed Cycloisomerization of Substituted 1,5-Hexadienes: A Combined Experimental and Computational Study on an Open and an Interrupted Hydropalladation/Carbopalladation/β-Hydride Elimination (HCHe) Catalytic Cycle

The PdII-catalyzed cycloisomerization of 3-alkoxycarbonyl-3-hydroxy-substituted
1,5-hexadienes has been studied experimentally and computationally.
Experimentally, the reaction is characterized by a rapid room temperature
formation of monomeric as well as dimeric cycloisomerization products
using the commercially available precatalyst [(CH3CN)4Pd]­(BF4)2. In situ NMR measurements
indicate the initial kinetic advantage of the desired cycloisomerization
pathway to methylene cyclopentanes; however, double bond isomerization,
elimination, and dimer formation are competitive undesired pathways.
Evaluation of the obtained product structures by NMR spectroscopy
and X-ray crystallography indicates that the sole determinant for
the monomer/dimer ratio is the regioselectivity of the initial hydropalladation
in favor of the allylic (monomer formation) or the homoallylic double
bond (dimer formation). In order to account for the experimental results,
we propose the coexistence of two product-forming catalytic cycles,
an open, monomer generating, as well as an interrupted and redirected,
dimer generating, hydropalladation/carbopalladation/β-hydride
elimination (HCHe) process. Results from computational studies of
the proposed competing catalytic cycles are supportive to our mechanistic
hypothesis and pinpoint the pivotal importance of PdII-hydroxo-chelate complexes for the reactivity–stability interplay of
on- and off-pathway intermediates.