Regioselectivity Control in Pd-Catalyzed Telomerization of Isoprene Enabled by Solvent and Ligand Selection

Abstract

Controlling the selectivity in palladium-catalyzed telomerization of nonsymmetric dienes represents a formidable challenge since up to 12 isomers can be obtained, and a general method for selective synthesis is still lacking. We select isoprene (2-methylbutadiene) as a representative and relevant example of a nonsymmetric diene. A combined experimental–computational study on a large set of phosphine-modified palladium catalysts and reaction conditions aiming to understand the factors governing the selectivity shows that it can be controlled by selecting the protic solvent pK a and by the ligand. Atomistic and kinetic simulations reveal that the solvent switches the selectivity-determining step as a function of pK a from C–C oxidative coupling at low pK a values (preference for telomer head-to-head) to protonation at high pK a values (preference for telomer tail-to-tail). The selectivity toward tail-to-head telomer can be directed in moderately acidic solvents by selection of the appropriate ligand, which exerts steric control of the protonation step. Thus, using Et2NH as a nucleophile, it was possible to synthesize 3 of the 4 main isomers in very high yields and selectivities and to provide a complete mechanistic picture of Pd-catalyzed telomerization of nonsymmetric dienes.

Isoprene Telomers for Biodiesel Applications

“…The reaction was carried out in the presence of catalytic amounts of Pd­(OAc) 2 (0.03 mol %) and PPh 3 (0.12 mol %). Small quantities of NaOH (0.2 mol %) were needed to facilitate the reduction of Pd­(II) to catalytically competent Pd(0) and promote the nucleophilic attack by the alcohol . GC-MS and NMR spectroscopic data collectively showed the formation of telomers after 30 h at 50 °C.…”

Indomuscone-Based Sterically Encumbered Phosphines as Ligands for Palladium-Catalyzed Reactions

“…Isoprene 7 and MeOH were used as substrates to assess not only the catalytic activity of the different phosphine ligands but also the selectivity toward the different products, which in this case arise from the head/tail potential couplings (Figure S3, top) . The catalytic results show that phosphine 2a outperforms triphenylphosphine 1a not only in catalytic activity but also, particularly, in selectivity, under the indicated reaction conditions (compare entries 1 and 2).…”

Nucleophilic aromatization of monoterpenes from isoprene under nickel/iodine cascade catalysis

“…In terms of the synthesis of hemiterpenoids, various catalytic systems have been well developed under transition metal catalysis 12 – 35 . Besides, with the regulation of ligand, Beller, Finn, Réau, Navarro, Carbó and our group reported palladium catalyzed nucleophilic telomerization of isoprene to produce acyclic monoterpenoids 32 , 36 – 44 . Using nickel-aminophosphinite complexes, different dimers of isoprene mixed together with low yields in Mortreux’s work 45 .…”