Mechanistic Investigation of the Palladium-Catalyzed Decarboxylative Cyclization of γ-Methylidene-δ-valerolactones with Isocyanates: Kinetic Studies and Origin of the Site Selectivity in the Nucleophilic Attack at a (π-Allyl)palladium

Abstract

Mechanistic studies for the palladium-catalyzed decarboxylative cyclization reactions of gamma-methylidene-delta-valerolactones 1 with isocyanates 2 are described. The reactions can be effectively catalyzed by palladium triarylphosphine complexes to give piperidones 3 and/or azaspiro[2.4]heptanones 4. Through kinetic studies using NMR spectroscopy, it has been determined that the oxidative addition of lactones 1 to palladium(0) is the turnover-limiting step of the catalytic cycle. By changes in the electronic properties of the triarylphosphine ligands, the product distribution between 3 and 4 can be easily controlled, and an explanation for the origin of this selectivity is provided. The selectivity between 3 and 4 is also influenced by the nature of the nitrogen substituent on isocyanates 2, and more electron-rich substituents tend to give higher selectivity toward azaspiro[2.4]heptanones 4. These studies represent the first systematic investigation into the selectivity between terminal attack and central attack at (pi-allyl)palladium species by nitrogen-based nucleophiles.

Pd‐Catalyzed Reaction of Allyl Carbonate with Polyols: The Role of CO2 in Transesterification versus Etherification of Glycerol

“…The results outlined above can be reconciled with the accepted mechanism for O-allylation, [5] if the resting state of the catalyst is the h 1 -or h 3 -allyl alkoxycarbonate complex (I/ II), [17,18] in equilibrium with a small proportion of the h 1 -allyl Pd alkoxide (III) and CO 2 ; [19] equilibrium with the ionic h 3allyl Pd alkoxide (IV), [20] then leads to irreversible O-allylation (D, Scheme 6).…”

Transition Metal-Catalyzed Decarboxylative Allylation and Benzylation Reactions

“…136 The regioselectivity of the lactamization is not affected by the aryl α-substituent of the lactone. Instead, the observed regioselectivity is dependent on the electronic effects imparted by the ligand on the metal center.…”

“…18 Thus, the observed decarboxylation of an α-alkyl malonate at 30 °C may provide insight regarding ways to lower the barriers for decarboxylation. 136 …”

Palladium‐Catalyzed Decarboxylative Intramolecular Aziridination from 4H‐Isoxazol‐5‐ones Leading to 1‐Azabicyclo[3.1.0]hex‐2‐enes

“…First, the oxidative addition of isoxazolone 1 a to a low-valent palladium center forms the six-membered palladacycle A, which readily undergoes decarboxylation [8,9] to give vinylnitrene/palladium complex B [10] and/or four-membered azapalladacyclobutene intermediate B'. First, the oxidative addition of isoxazolone 1 a to a low-valent palladium center forms the six-membered palladacycle A, which readily undergoes decarboxylation [8,9] to give vinylnitrene/palladium complex B [10] and/or four-membered azapalladacyclobutene intermediate B'.…”

“…Ligand Conversion [%] [b] Yield [%] [b] 1 Scheme 2 shows a proposed catalytic cycle for the palladium-catalyzed intramolecular aziridination reaction of methallyl-substituted 4H-isoxazol-5-one 1 a. First, the oxidative addition of isoxazolone 1 a to a low-valent palladium center forms the six-membered palladacycle A, which readily undergoes decarboxylation [8,9] to give vinylnitrene/palladium complex B [10] and/or four-membered azapalladacyclobutene intermediate B'. [11] Then, cycloaddition of the tethered alkene gives two possible azapalladacycles C and C'.…”