Simon J. Garden

A versatile synthetic methodology for the synthesis of tryptophols

Tryptophols have been obtained in high yields by the reduction of 3-substituted-dioxindoles (obtained by the aldol condensation reaction of ketones with isatins or by a modified Knovenagel malonate condensation) using a borane tetrahydrofuran complex. The reported methodology offers distinct advantages over existing methods for the synthesis of these compounds, including consistently greater yields, diastereoselective syntheses and the possibility for the synthesis of a wide range of structurally different tryptophols. The reduction reaction was found to proceed via an intermediate 1,3-diol-oxindole, which was obtained diastereoselectively and, which was subsequently reduced to the corresponding tryptophol.

A modified Sandmeyer methodology and the synthesis of (±)-convolutamydine A

Abstract (±)-Convolutamydine A ( 5 ) has been prepared by a concise synthesis form 3,5-dibromoaniline using a modified Sandmeyer methodology. The modified Sandmeyer methodology has also been found to be beneficial for the synthesis of other α-isonitrosoacetanilides. The 4,6-dibromohydrocyoxindole nucleus was further confirmed by comparison with the isomeric 5,7-dibromohydroxyoxindole.

The Three‐Component Biginelli Reaction: A Combined Experimental and Theoretical Mechanistic Investigation

Biginelli reactions have been monitored by direct infusion electrospray ionization mass spectrometry (ESI-MS) and key cationic intermediates involved in this three-component reaction have been intercepted and further characterized by tandem MS experiments (ESI-MS/MS). Density functional theory calculations were also used to investigate the feasibility of the major competing mechanisms proposed for the Biginelli reaction. The experimental and theoretical results were found to corroborate the iminium mechanism proposed by Folkers and Johnson, whereas no intermediates directly associated with either the more energy demanding Knoevenagel or enamine mechanisms could be intercepted.

A Convenient Methodology for the N-Alkylation of Isatin Compounds

Abstract A simple, high yielding, methodology for the N-alkylation of substituted isatin derivatives using calcium hydride in DMF is detailed.

Isatin derivatives are reactive electrophilic components for the Baylis–Hillman reaction

Abstract Isatin derivatives readily react as the electrophilic component in the Baylis–Hillman reaction giving good to excellent yields of the respective adducts. It is generally accepted that ketones only take part in the Baylis–Hillman reaction under relatively extreme conditions, with a few exceptions. Isatin on the other hand readily reacts with acrylic acid derivatives in ethanol and or ethanol/THF mixtures in the presence of a catalytic quantity of DABCO. The solid state structures for these novel dioxindole derivatives were determined for two adducts by single-crystal X-ray diffraction spectroscopy, revealing an inside hydroxyl conformation.

Synthesis of 1-ferrocenyl-2-aryl(heteroaryl)acetylenes and 2-ferrocenylindole derivatives via the Sonogashira–Heck–Cassar reaction

Abstract The Sonogashira–Heck–Cassar reaction of ferrocenylacetylene with aryl- and heteroaryl halides was shown to be a facile and convenient route for the synthesis of 1-ferrocenyl-2-aryl- and 1-ferrocenyl-2-heteroarylacetylenes in high yields. Additionally, annulation reactions of some of the 1-ferrocenylacetylene compounds gave 2-ferrocenyl-2-benzo[ b ]furan and 2-ferrocenylindoles in good yields.

Aromatic iodination in aqueous solution. A new lease of life for aqueous potassium dichloroiodate

Abstract A re-investigation of the use of aqueous potassium dichloroiodate (KICl 2 ) as an iodinating agent for aromatic compounds has found the reagent to be more generally applicable than previously known. The reagent has been found to give excellent yields of iodinated heterocyclic compounds, such as isatin, imidazole and pyrazole.

C−H Functionalization of 1,4-Naphthoquinone by Oxidative Coupling with Anilines in the Presence of a Catalytic Quantity of Copper(II) Acetate

The oxidative addition of anilines (2) with 1,4-naphthoquinone (3) to give N-aryl-2-amino-1,4-naphthoquinones (1) was found to be catalyzed by copper(II) acetate. In the absence of the catalyst, the reactions are slower and give lower yields with the formation of many colateral products. In the presence of 10 mol % hydrated copper(II) acetate, the reactions are generally more efficient in that they are cleaner, higher yielding, and faster.

Single-Component Phosphinous Acid Ruthenium(II) Catalysts for Versatile C−H Activation by Metal–Ligand Cooperation

Well-defined ruthenium(II) phosphinous acid (PA) complexes enabled chemo-, site-, and diastereoselective C-H functionalization of arenes and alkenes with ample scope. The outstanding catalytic activity was reflected by catalyst loadings as low as 0.75 mol %, and the most step-economical access reported to date to angiotensin II receptor antagonist blockbuster drugs. Mechanistic studies indicated a kinetically relevant C-X cleavage by a single-electron transfer (SET)-type elementary process, and provided evidence for a PA-assisted C-H ruthenation step.

A synthesis of 3-fluoroindoles and 3,3-difluoroindolines by reduction of 3,3-difluoro-2-oxindoles using a borane tetrahydrofuran complex

Abstract A borane tetrahydrofuran complex has been used to study the reduction of 3,3-difluoro-2-oxindoles and been found to yield either 3-fluoroindoles or 3,3-difluoroindolines. The latter have been found to be reasonably stable when the aromatic nucleus is substituted with an electron withdrawing group and are in these cases the predominant product. The efficient synthesis of the former occurs by climination of HF in the presence of silica from the latter. The 3,3-difluoro-2-oxindoles were prepared by the reaction of appropriately substituted isatin derivatives with DAST.