Palladium-Catalyzed Synthesis of Linked Bis-Heterocycles─Synthesis and Investigation of Photophysical Properties.

A palladium-catalyzed domino C-N coupling/Cacchi reaction is reported. Design of photoluminescent bis-heterocycles, aided by density functional theory calculations, was performed with synthetic yields up to 98%. The photophysical properties of the products accessed via this strategy were part of a comprehensive study that led to broad emission spectra and quantum yields of up to 0.59. Mechanistic experiments confirmed bromoalkynes as competent intermediates, and a density functional theory investigation suggests a pathway involving initial oxidative addition into the cis C-Br bond of the gem-dihaloolefin.

Pd(0)/Blue Light Promoted Carboiodination Reaction - Evidence for Reversible C-I Bond Formation via a Radical Pathway.

A Pd(0)/blue light catalyzed carboiodination reaction is reported. A simple, air-stable catalytic system, utilizing [Pd(allyl)Cl]2 and DPEPhos, generated a variety of iodinated hetero- and carbocycles including oxindoles, dihydrobenzofurans, indolines, a chromane, and a tetrahydronaphthalene. This protocol was tolerant of sensitive functional groups including free carboxylic acids, phenols, and anilines, as well as pyridines, while delivering products in up to 94% yield. Support for a reversible C-I bond formation via a single electron mechanism was obtained using a deuterium labeled substrate and a stoichiometric neopentylpalladium species.

A Modular Approach for the Palladium-Catalyzed Synthesis of Bis-heterocyclic Spirocycles.

A simple and modular approach toward bis-heterocyclic spirocycles using palladium catalysis is reported. The enclosed methodology leverages a Mizoroki-Heck-type reaction to generate a neopentylpalladium species. This species can undergo intramolecular C-H activation on a wide array of (hetero)aryl C-H bonds, generating a variety of [4.4] and [4.5] bis-heterocyclic spirocycles in up to 95% yield. A diverse range of bis-heterocyclic spirocycles were possible, with 24 examples and 18 different combinations of heterocycles were synthesized. Biologically relevant aza-heterocycles such as purine, pyrazole, (benz)imidazole, (aza)indole, and pyridine were readily incorporated into the spirocyclic core. The reaction was readily scalable to 1 mmol using a lower catalyst loading and number of base equivalents, and the product was purified without the use flash column chromatography.

A DFT examination of the role of proximal boron functionalities in the S-alkylation of sulfenic acid anions.

Sulfenic acid anions represent an emerging nucleophile for the preparation of sulfoxides. Their S-functionalization chemistry can often be influenced by a nearby group that interacts with the component atoms of the sulfenate through non-bonding interactions. This study uses DFT methods to assess the importance of proximal boron-containing functional groups to direct S-alkylation chemistry of selected sulfenate anions. Several structural variations were modelled at the B3LYP/6-311++G(d,p) level, with the boron species positioned 3 to 5 carbons away from the alkylation site. Transition state free energies of S-alkylation transition states were located with and without sulfenate oxygen precomplexing to the nearby boron atom. The outcomes suggest that an ortho-substituted boronate ester on benzyl bromide can direct and accelerate an alkylation reaction principally due to a reduction of the entropic barrier. It was also determined that an intermolecular precomplex imparts too much stabilization to the sulfenate, thereby reducing its reactivity. The modelling suggests a possible aryl migration of the boronate/sulfenate complex is not competitive with S-alkylation.