Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams

The enantioselective synthesis of nitrogen-containing heterocycles (N-heterocycles) represents a substantial chemical research effort and resonates across numerous disciplines, including the total synthesis of natural products and medicinal chemistry. In this Article, we describe the highly enantioselective palladium-catalysed decarboxylative allylic alkylation of readily available lactams to form 3,3-disubstituted pyrrolidinones, piperidinones, caprolactams and structurally related lactams. Given the prevalence of quaternary N-heterocycles in biologically active alkaloids and pharmaceutical agents, we envisage that our method will provide a synthetic entry into the de novo asymmetric synthesis of such structures. As an entry for these investigations we demonstrate how the described catalysis affords enantiopure quaternary lactams that intercept synthetic intermediates previously used in the synthesis of the Aspidosperma alkaloids quebrachamine and rhazinilam, but that were previously only available by chiral auxiliary approaches or as racemic mixtures

Boc保護イミン前駆体としてのBoc保護アミナールの開発と合成反応への応用

京都大学0048新制・課程博士博士(理学)甲第17773号理博第3896号新制||理||1562(附属図書館)30580京都大学大学院理学研究科化学専攻(主査)教授 丸岡 啓二, 教授 大須賀 篤弘, 教授 時任 宣博学位規則第4条第1項該当Doctor of ScienceKyoto UniversityDGA

Friedel−Crafts‐Type Allylation of Phenol Derivatives Catalyzed by In Situ‐Generated Silyl Cyanometallates

We successfully demonstrated that Friedel−Crafts‐type allylation of phenol derivatives and allylic phosphates is catalyzed by the AgTFA/trimethylsilyl cyanide (Me3SiCN) and Pd(OAc)2/Me3SiCN combined systems to afford the C‐allylated product in a highly regioselective manner. The corresponding silyl cyanometallates generated in situ are proposed to be the active catalytic species. Lewis acidity of the reversibly formed ion pairs is appropriately regulated for this reaction. The para‐allylated anisole and phenol derivatives are selectively obtained. The para‐substituted ones are converted to the ortho‐allylated products. The reactivity of the catalytic systems is strongly dependent on the electronic nature of both electrophile and nucleophile. Substitution of an aromatic ring on the allylic phosphate is essential for the reaction. Thus, the competitive reaction of a 1 : 1 mixture of cinnamyl and simple allyl phosphates affords only the cinnamyl‐substituted product

Silyl Cyanopalladate-Catalyzed Friedel-Crafts-Type Cyclization Affording 3-Aryloxindole Derivatives

3-Aryloxindole derivatives were synthesized through a Friedel-Crafts-type cyclization. The reaction was catalyzed by a trimethylsilyl tricyanopalladate complex generated in situ from trimethylsilyl cyanide and Pd(OAc)(2). Wide varieties of diethyl phosphates derived from N-arylmandelamides were converted almost quantitatively into oxindoles. When N,N-dibenzylamide was used instead of an anilide substrate, a benzo-fused delta-lactam was obtained. An oxindole product was subjected to substitution reactions to afford 3,3-diaryloxindoles with two different aryl groups

Planar and Bent BN-Embedded <i>p</i>‑Quinodimethanes Synthesized by Transmetalation of Bis(trimethylsilyl)-1,4-dihydropyrazines with Chloroborane

Two BN-embedded <i>p</i>-quinodimethane derivatives were synthesized by a reaction of bis­(trimethylsilyl)-1,4-dihydropyrazines, which are known as inorganic-salt-free reductants, with 9-chloro-9-borafluorene. The planar or bent structures of the resulting π-conjugated compounds were revealed by X-ray diffraction analysis. Their photophysical properties relate to their planar or bent structures due to the difference in the distribution of the HOMO

Planar and Bent BN-Embedded <i>p</i>‑Quinodimethanes Synthesized by Transmetalation of Bis(trimethylsilyl)-1,4-dihydropyrazines with Chloroborane

Two BN-embedded <i>p</i>-quinodimethane derivatives were synthesized by a reaction of bis­(trimethylsilyl)-1,4-dihydropyrazines, which are known as inorganic-salt-free reductants, with 9-chloro-9-borafluorene. The planar or bent structures of the resulting π-conjugated compounds were revealed by X-ray diffraction analysis. Their photophysical properties relate to their planar or bent structures due to the difference in the distribution of the HOMO