Regioselective catalytic acetoxylation of limonene

Abstract

Two efficient strategies for a direct catalytic and regioselective acetoxylation of terpenes are described.Acetoxylated limonene derivatives were synthesized via palladium-catalyzed C-H activation utilizing para-benzoquinone (BQ) as reoxdidation agent and acetic acid as solvent and reactant. Addition of dimethyl sulfoxide (DMSO) to the catalytic system led to highly selective functionalization of the exocyclic double bond of limonene. This catalytic acetoxylation of limonene was further optimized with regard to a more sustainable and environmentally-friendly procedure. On the other hand, the use of an aerobic tandem catalytic system using iron(II) phthalocyanine (Fe(Pc)) as co-catalyst, which acts as electron transfer mediator (ETM), enabled a highly selective acetoxylation of the endocyclic double bond of limonene with high conversions. Moreover, diacetoxylated products were prepared by a reaction sequence applying the aforementioned catalytic systems.

Selective Catalytic Epoxide Ring-Opening of Limonene Dioxide with Water

“…For instance, palladium catalysts have been used for the allylic C−H oxidation 19 and acetoxylation 20 of several substrates as well as the selective acetoxylation of limonene. 21 In contrast to catalysts such as palladium acetate, supported palladium nanoparticles as heterogeneous catalysts offer the advantages of metal catalysis combined with the benefit of a simplified catalyst recycling. For example, palladium nanoparticles supported on TiO 2 were used for the allylic C−H acetoxylation of terminal alkenes.…”

“…Generally, palladium was shown to be a highly useful catalyst for many different reactions. For instance, palladium catalysts have been used for the allylic C–H oxidation and acetoxylation of several substrates as well as the selective acetoxylation of limonene . In contrast to catalysts such as palladium acetate, supported palladium nanoparticles as heterogeneous catalysts offer the advantages of metal catalysis combined with the benefit of a simplified catalyst recycling.…”

Palladium-Catalyzed Regioselective Allylic Oxidation of Amorphadiene, a Precursor of Artemisinin

“…[8][9][10][11][12][13][14][15][16][17][18][19] While the process seems to be favored in the case of intracyclic double bonds, achieving high selectivity for terminal disubstitued olefins is highly challenging. 17 Beside this key endeavor, AD possesses five allylic positions which can potentially react, and the development of a catalytic system allowing a regioselective allylic oxidation constitutes a synthetic challenge. With this goal in mind, we report herein the development of a regioselective Pd-catalyzed oxidation of AD to artemisinic alcohol 1, a key intermediate in the synthesis of AA and artemisinin (Scheme 1, eq 3).…”

“…Scheme 1: a) Current fermentation process to produce AA (eq 1); b) biosynthesis of AA from AD (eq 2), and; c) This work: development of a Pd-catalyzed allylic oxidation of AD to produce AA (eq 3) Among the different methods reported, the regioselective oxidation of limonene published by Meier et al 17 using Pd(OAc)2 (15 mol %) and p-benzoquinone (BQ, 2 equiv), in DMSO/AcOH at 50 °C for 24 h, appeared to be the most promising method. However, our first attempts to apply the exact literature conditions to AD afforded poor reactivity and degradation of AD.…”

“…Several methods related to the allylic oxidation or “anti-Wacker” oxidation of terminal olefins have been reported. These methods require a metal catalyst, such as Cu or Pd, a ligand, a base, and an oxidant. − While the process seems to be favored in the case of intracyclic double bonds, achieving high selectivity for terminal disubstitued olefins is highly challenging . Beside this key endeavor, AD possesses five allylic positions which can potentially react, and the development of a catalytic system allowing a regioselective allylic oxidation constitutes a synthetic challenge.…”