Surprising Route to a Monoazaporphyrin and Full Characterization of Its Complexes with Five Different 3d Metals.

In the search for mild agents for the oxidative cyclization of tetrapyrromethane to the corresponding corrole, we discovered a route that leads to a monoazaporphyrin with three meso-CF3 groups. Optimization studies that allowed access to appreciable amounts of this new macrocycle paved the way for the preparation of its cobalt, copper, nickel, zinc, and iron complexes. All complexes were fully characterized by various spectroscopic methods and X-ray crystallography. Their photophysical and electrochemical properties were determined and compared to those of analogous porphyrins in order to deduce the effect of the peripheral N atom. Considering the global efforts for designing efficient alternatives to platinum group metal (PGM) catalysts, they were also absorbed onto a porous carbon electrode material and studied as electrocatalysts for the oxygen reduction reaction (ORR). The cobalt complex was found to be operative at a quite positive catalytic onset potential and with good selectivity for the desirable 4-electrons/4-protons pathway.

Total Synthesis of Aleutianamine.

Aleutianamine is a recently isolated pyrroloiminoquinone natural product that displays potent and selective biological activity toward human pancreatic cancer cells with an IC50 of 25 nM against PANC-1, making it a potential candidate for therapeutic development. We report a synthetic approach to aleutianamine wherein the unique [3.3.1] ring system and tertiary sulfide of this alkaloid were constructed via a novel palladium-catalyzed dearomative thiophene functionalization. Other highlights of the synthesis include a palladium-catalyzed decarboxylative pinacol-type rearrangement of an allylic carbonate to install a ketone and a late-stage oxidative amination. This concise and convergent strategy will enable access to analogues of aleutianamine and further investigation of the biological activity of this unique natural product.

Part-per-Trillion Trace Selective Gas Detection Using Frequency Locked Whispering-Gallery Mode Microtoroids.

Rapid detection of toxic and hazardous gases at trace concentrations plays a vital role in industrial, battlefield, and laboratory scenarios. Of interest are both sensitive as well as highly selective sensors. Whispering-gallery mode (WGM) microresonator-based biochemical sensors are among the most sensitive sensors in existence due to their long photon confinement times. One main concern with these devices, however, is their selectivity toward specific classes of target analytes. Here, we employ frequency locked WGM microtoroid optical resonators covalently modified with various polymer coatings to selectively detect the chemical warfare agent surrogate diisopropyl methylphosphonate (DIMP) as well as the toxic industrial chemicals formaldehyde and ammonia at parts-per-trillion concentrations (304, 434, and 117 ppt, respectively). This is 1-2 orders of magnitude better than previously reported, depending on the target, except for pristine graphene and pristine carbon nanotube sensors, which demonstrate similar detection levels but in vacuum and without selectivity. Selective polymer coatings include polyethylene glycol for DIMP sensing, accessed by the modification of commercially available materials, and 3-(triethoxysilyl) propyl-terminated polyvinyl acetate (PVAc) for ammonia sensing. Notably, we developed for the first time an efficient one-pot procedure to access 3-(triethoxysilyl) propyl-terminated PVAc that utilizes cobalt-mediated living radical polymerization and a nitroxyl polymer-terminating agent. Alkaline hydrolysis of PVAc coatings to form polyvinyl alcohol coatings directly bound to the microtoroid proved to be reliable and reproducible, leading to WGM sensors capable of the rapid and selective detection of formaldehyde vapors. The selectivity of these three polymer coatings as sensing media was predicted, in part, based on their functional group content and known reactivity patterns with the target analytes. Furthermore, we demonstrate that microtoroids coated with a mixture of polymers can serve as an all-in-one sensor that can detect multiple agents. We anticipate that our results will facilitate rapid early detection of chemical agents, as well as their surrogates and precursors.

Ir-Catalyzed Asymmetric Allylic Alkylation of Dialkyl Malonates Enabling the Construction of Enantioenriched All-Carbon Quaternary Centers.

An enantioselective iridium-catalyzed allylic alkylation of malonates with trisubstituted allylic electrophiles to form all-carbon quaternary stereocenters is reported. This reaction proceeds at ambient temperature and enables the preparation of a wide range of enantioenriched products in up to 93% yield and 97% ee. The quaternary products can be readily converted to several valuable building blocks such as vicinal quaternary products and ß-quaternary acids.

Synthesis of Enantioenriched gem-Disubstituted 4-Imidazolidinones by Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation.

A variety of enantioenriched gem-disubstituted 4-imidazolidinones were prepared in up to >99% yield and 95% ee by the Pd-catalyzed decarboxylative asymmetric allylic alkylation of imidazolidinone-derived ß-amidoesters. In the process of preparing these substrates, a rapid synthetic route to 4-imidazolidinone derivatives was developed, beginning from 2-thiohydantoin. The orthogonality of the benzoyl imide and tert-butyl carbamate groups used to protect these nitrogen-rich products was demonstrated, enabling potential applications in drug design.

Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation of 1,4-Diazepan-5-ones.

We report the palladium-catalyzed asymmetric allylic alkylation of 1,4-diazepan-5-ones. This reaction proceeds smoothly to give gem-disubstituted diazepanone heterocycles bearing various functional groups in up to >99% yield and up to 95% ee. An electron-rich p-anisoyl lactam protecting group and the use of a nonpolar solvent proved crucial to obtaining high enantioselectivity in most cases. Additionally, we demonstrate the use of our methodology in the synthesis of a gem-disubstituted analogue of the FDA-approved anti-insomnia drug suvorexant.