Total Synthesis of (−)-Rhazinilam and Formal Synthesis of (+)-Eburenine and (+)-Aspidospermidine: Asymmetric Cu-Catalyzed Propargylic Substitution

A total synthesis of (−)-rhazinilam and formal syntheses of (+)-eburenine and (+)-aspidospermidine that rely on a copper­(I)-catalyzed asymmetric propargylic substitution as the key step are reported. A salient feature of the reaction is the asymmetric construction of a quaternary stereocenter in high yield and enantiomeric excess

Expedient Preparation of Trifluoromethyl-Substituted Benzofuranols

Direct access to 3-trifluoromethyl-substituted benzofuranols is presented. The products are obtained in good yields from commercially available salicylaldehydes by using in situ generated trifluoromethyl diazomethane and boron trifluoride as an activator. As shown in a representative example, the products can be transformed into the corresponding trifluoromethyl-substituted benzofurans

Total Synthesis of (±)-Gelsemoxonine

Gelsemoxonine (<b>1</b>) is a <i>Gelsemium</i> alkaloid incorporating an unusual azetidine. Its total synthesis was achieved employing a novel ring contraction of a spirocyclopropane isoxazolidine to furnish a β-lactam intermediate. This β-lactam ring was further elaborated into the azetidine of Gelsemoxonine. In addition, the synthesis includes a highly diastereoselective reductive Heck cyclization for the installation of the oxindole ring system as well as a directed hydrosilylation of an alkyne to access the ethyl ketone of the natural product

Total Synthesis of Gelsemoxonine through a Spirocyclopropane Isoxazolidine Ring Contraction

Plants of the species Gelsemium have found application in traditional Asian medicine for over a thousand years. Gelsemoxonine represents a novel constituent of this plant incorporating a highly functionalized azetidine at its core. We herein report a full account of our studies directed toward the total synthesis of gelsemoxonine that relies on a conceptually new approach for the construction of the central azacyclobutane. A spirocyclopropane isoxazolidine ring contraction was employed to access a key β-lactam intermediate, which could be further elaborated to the azetidine of the natural product. In the course of our studies, we have gained detailed insight into this intriguing transformation. Furthermore, we report on previously unnoticed oligomerization chemistry of gelsemoxonine. We also document an enantioselective synthesis of a key precursor en route to gelsemoxonine

Rh-Catalyzed Stereospecific Synthesis of Allenes from Propargylic Benzoates and Arylboronic Acids

An enantiospecific approach to the synthesis of optically active, trisubstituted allenes from chiral propargylic benzoates and arylboronic acids has been developed. The transformation is catalyzed by a Rh–(P,olefin) complex formed <i>in situ</i> from [{Rh­(cod)­Cl}₂] and a readily available phosphoramidite ligand. The method furnishes an assortment of diverse allenes in high yields and excellent enantiospecificity under mild conditions

Total Synthesis of (±)-Gelsemoxonine

Gelsemoxonine (<b>1</b>) is a <i>Gelsemium</i> alkaloid incorporating an unusual azetidine. Its total synthesis was achieved employing a novel ring contraction of a spirocyclopropane isoxazolidine to furnish a β-lactam intermediate. This β-lactam ring was further elaborated into the azetidine of Gelsemoxonine. In addition, the synthesis includes a highly diastereoselective reductive Heck cyclization for the installation of the oxindole ring system as well as a directed hydrosilylation of an alkyne to access the ethyl ketone of the natural product

Ir-Catalyzed Preparation of SF₅‑Substituted Potassium Aryl Trifluoroborates via C–H Borylation and Their Application in the Suzuki–Miyaura Reaction

The preparation of new pentafluorosulfanyl-substituted potassium aryltrifluoroborates via Ir-catalyzed C–H borylation is reported. The utility of these novel building blocks was demonstrated in the Suzuki–Miyaura cross-coupling reaction, giving access to 3,5-disubstituted pentafluorosulfanylbenzenes

Total Synthesis of Gelsemoxonine through a Spirocyclopropane Isoxazolidine Ring Contraction

Plants of the species Gelsemium have found application in traditional Asian medicine for over a thousand years. Gelsemoxonine represents a novel constituent of this plant incorporating a highly functionalized azetidine at its core. We herein report a full account of our studies directed toward the total synthesis of gelsemoxonine that relies on a conceptually new approach for the construction of the central azacyclobutane. A spirocyclopropane isoxazolidine ring contraction was employed to access a key β-lactam intermediate, which could be further elaborated to the azetidine of the natural product. In the course of our studies, we have gained detailed insight into this intriguing transformation. Furthermore, we report on previously unnoticed oligomerization chemistry of gelsemoxonine. We also document an enantioselective synthesis of a key precursor en route to gelsemoxonine

Total Synthesis of Gelsemoxonine through a Spirocyclopropane Isoxazolidine Ring Contraction

Plants of the species Gelsemium have found application in traditional Asian medicine for over a thousand years. Gelsemoxonine represents a novel constituent of this plant incorporating a highly functionalized azetidine at its core. We herein report a full account of our studies directed toward the total synthesis of gelsemoxonine that relies on a conceptually new approach for the construction of the central azacyclobutane. A spirocyclopropane isoxazolidine ring contraction was employed to access a key β-lactam intermediate, which could be further elaborated to the azetidine of the natural product. In the course of our studies, we have gained detailed insight into this intriguing transformation. Furthermore, we report on previously unnoticed oligomerization chemistry of gelsemoxonine. We also document an enantioselective synthesis of a key precursor en route to gelsemoxonine

Formaldehyde <i>N</i>,<i>N</i>‑Dialkylhydrazones as Neutral Formyl Anion Equivalents in Iridium-Catalyzed Asymmetric Allylic Substitution

The use of formaldehyde <i>N</i>,<i>N</i>-dialkylhydrazones as neutral C1-nucleophiles in the iridium-catalyzed substitution of allylic carbonates is described for two processes. Kinetic resolution or, alternatively, stereospecific substitution affords configurationally stable α,α-disubstituted aldehyde hydrazones in high enantiomeric excess and yield. This umpolung approach allows for the construction of optically active allylic nitriles and dithiolanes as well as branched α-aryl aldehydes. A catalyst-controlled reaction with Enders’ chiral hydrazone derivatives followed by diastereoselective nucleophilic addition to the hydrazone products constitutes a two-step stereodivergent synthesis of chiral amines