Aromatic C-H amination in hexafluoroisopropanol.

We report a direct radical aromatic amination reaction that provides unprotected anilines with an improvement in the substrate scope compared to prior art. Hydrogen bonding by the solvent hexafluoroisopropanol to anions of cationic species is responsible for increased reactivity and can rationalize the enhancement in substrate scope. Our findings may have bearings on radical additions to arenes for direct C-H functionalization in general.

18F-Deoxyfluorination of Phenols via Ru π-Complexes.

The deficiency of robust and practical methods for 18F-radiofluorination is a bottleneck for positron emission tomography (PET) tracer development. Here, we report the first transition-metal-assisted 18F-deoxyfluorination of phenols. The transformation benefits from readily available phenols as starting materials, tolerance of moisture and ambient atmosphere, large substrate scope, and translatability to generate doses appropriate for PET imaging.

Applications of protein engineering to members of the old yellow enzyme family.

In the 20 years since Massey's initial report in 1995, interest in using alkene reductases to prepare chiral intermediates for synthesis has grown rapidly. While native alkene reductases often show very high stereoselectivities toward favorable substrates, these enzymes have somewhat size-restricted active sites that limit their substrate ranges to small alkenes. In addition, most alkene reductases have the same stereoselectivities, which makes it difficult to access the "other" product enantiomers. Protein engineering strategies have been used to address both of these issues and good progress has been made in several cases. This review summarizes published examples through late 2014 and focuses on studies of six enzymes: Saccharomyces pastorianus OYE 1, tomato OPR1, Zymomonas mobilis NCR, Enterobacter cloacae PB2 PETN reductase, Bacillus subtilis YqjM and Pichia stipitis OYE 2.6.

Selective Aromatic C-H Hydroxylation Enabled by η6-Coordination to Iridium(III).

We report an aromatic C-H hydroxylation protocol in which the arene is activated through η6-coordination to an iridium(III) complex. η6-Coordination of the arene increases its electrophilicity and allows for high positional selectivity of hydroxylation at the site of least electron density. Through investigation of intermediate η5-cyclohexadienyl adducts and arene exchange reactions, we evaluate incorporation of arene π-activation into a catalytic cycle for C-H functionalization.

Investigation of fluorinated and bifunctionalized 3-phenylchroman-4-one (isoflavanone) aromatase inhibitors.

Fluorinated isoflavanones and bifunctionalized isoflavanones were synthesized through a one-step gold(I)-catalyzed annulation reaction. These compounds were evaluated for their in vitro inhibitory activities against aromatase in a fluorescence-based enzymatic assay. Selected compounds were tested for their anti-proliferative effects on human breast cancer cell line MCF-7. Compounds 6-methoxy-3-(pyridin-3-yl)chroman-4-one (3c) and 6-fluoro-3-(pyridin-3-yl)chroman-4-one (3e) were identified as the most potent aromatase inhibitors with IC50 values of 2.5 µM and 0.8 µM. Therefore, these compounds have great potential for the development of pharmaceutical agents against breast cancer.

Engaging unactivated alkyl, alkenyl and aryl iodides in visible-light-mediated free radical reactions.

Radical reactions are a powerful class of chemical transformations. However, the formation of radical species to initiate these reactions has often required the use of stoichiometric amounts of toxic reagents, such as tributyltin hydride. Recently, the use of visible-light-mediated photoredox catalysis to generate radical species has become popular, but the scope of these radical precursors has been limited. Here, we describe the identification of reaction conditions under which photocatalysts such as fac-Ir(ppy)3 can be utilized to form radicals from unactivated alkyl, alkenyl and aryl iodides. The generated radicals undergo reduction via hydrogen atom abstraction or reductive cyclization. The reaction protocol utilizes only inexpensive reagents, occurs under mild reaction conditions, and shows exceptional functional group tolerance. Reaction efficiency is maintained upon scale-up and decreased catalyst loading, and the reaction time can be significantly shortened when the reaction is performed in a flow reactor.

Development of a new class of aromatase inhibitors: design, synthesis and inhibitory activity of 3-phenylchroman-4-one (isoflavanone) derivatives.

Aromatase (CYP19) catalyzes the aromatization reaction of androgen substrates to estrogens, the last and rate-limiting step in estrogen biosynthesis. Inhibition of aromatase is a new and promising approach to treat hormone-dependent breast cancer. We present here the design and development of isoflavanone derivatives as potential aromatase inhibitors. Structural modifications were performed on the A and B rings of isoflavanones via microwave-assisted, gold-catalyzed annulation reactions of hydroxyaldehydes and alkynes. The in vitro aromatase inhibition of these compounds was determined by fluorescence-based assays utilizing recombinant human aromatase (baculovirus/insect cell-expressed). The compounds 3-(4-phenoxyphenyl)chroman-4-one (1h), 6-methoxy-3-phenylchroman-4-one (2a) and 3-(pyridin-3-yl)chroman-4-one (3b) exhibited potent inhibitory effects against aromatase with IC(50) values of 2.4 µM, 0.26 µM and 5.8 µM, respectively. Docking simulations were employed to investigate crucial enzyme/inhibitor interactions such as hydrophobic interactions, hydrogen bonding and heme iron coordination. This report provides useful information on aromatase inhibition and serves as a starting point for the development of new flavonoid aromatase inhibitors.