Three-Component Olefin Dicarbofunctionalization Enabled by Nickel/Photoredox Dual Catalysis.

An intermolecular, photocatalytic dicarbofunctionalization (DCF) of olefins enabled by the merger of Giese-type addition with Ni/photoredox dual catalysis has been realized. Capitalizing on the rapid addition of 3° radicals to alkenes and their reluctance toward single electron metalation to Ni complexes, regioselective alkylation and arylation of olefins is possible. This dual catalytic method not only permits elaborate species to be assembled from commodity materials, but also allows quaternary and tertiary centers to be installed in a singular, chemoselective olefin difunctionalization. This multicomponent process occurs under exceptionally mild conditions, compatible with a diverse range of functional groups and synthetic handles such as pinacolboronate esters. This technology was directly applied to the synthesis of an intermediate to a preclinical candidate (TK-666) and its derivatives.

Spray Pyrolysis as a Combinatorial Method for the Generation of Photocatalyst Libraries.

An inexpensive, combinatorial method to evaluate an array of metal oxide materials as photocatalysts for solar fuel production utilizing spray pyrolysis is presented. This new approach capitalizes on the inherent properties of spray pyrolysis. We take advantage of the natural lateral gradient produced in a spray cone to fashion four-metal-three-at-a-time compositional triangular patterns on conductive glass substrates from simple nitrate salt precursor solutions. Subsequent annealing produces thin-film electrodes that are readily screened for photochemical activity using a simple laser scanner system. The apparatus employed is constructed from readily available commercial components, making it accessible to a wide number of laboratories. Our method complements other combinatorial methods in that it provides a chemically different environment for the formation of materials that might produce different morphologies and metal oxidation states and it allows for easy evaluation of layered structures, as well single-phase materials, thereby expanding the number of unique materials tested as potential photocatalysts. As a proof of principle, the discovery and optimization of a new Na-doped CuBi2O4 photocatalyst is described.

3-Boryl-2,1-borazaronaphthalene: Umpolung Reagents for Diversifying Naphthalene Isosteres.

A Pd-catalyzed Miyaura borylation of 3-bromo-2,1-borazaronaphthalenes is reported. This method allows the formation of umpolung reagents for subsequent Pd-mediated cross-coupling. Coupling of this nucleophilic partner with a variety of commercially available aryl- and heteroaryl halides allows facile and rapid diversification of these cores.

Redox-Neutral Photocatalytic Cyclopropanation via Radical/Polar Crossover.

A benchtop stable, bifunctional reagent for the redox-neutral cyclopropanation of olefins has been developed. Triethylammonium bis(catecholato)iodomethylsilicate can be readily prepared on multigram scale. Using this reagent in combination with an organic photocatalyst and visible light, cyclopropanation of an array of olefins, including trifluoromethyl- and pinacolatoboryl-substituted alkenes, can be accomplished in a matter of hours. The reaction is highly tolerant of traditionally reactive functional groups (carboxylic acids, basic heterocycles, alkyl halides, etc.) and permits the chemoselective cyclopropanation of polyolefinated compounds. Mechanistic interrogation revealed that the reaction proceeds via a rapid anionic 3- exo- tet ring closure, a pathway consistent with experimental and computational data.