José A. Souto

Iodine(III)-mediated intermolecular allylic amination under metal-free conditions.

A new approach to direct intermolecular allylic amination has been developed using metal-free conditions at room temperature. The reaction employs a hypervalent iodine(III) reagent as an oxidant and bistosylimide as a nitrogen source. A series of different allylic aminations are presented with up to a 99% yield. Mechanistic studies including isotope labeling and Hammett correlation suggest that depending on the substrate structure two different mechanisms can be operating.

Iodine(III)‐Promoted Intermolecular Diamination of Alkenes

A rapid and productive vicinal diamination of alkenes takes place in the presence of a hypervalent iodine(III) reagent and bissulfonimides as nitrogen sources. A total of more than 60 examples are presented. The reaction is characterized by its robustness and its wide substrate scope: it proceeds selectively with both terminal and internal alkenes and tolerates a range of functional groups.

Indole Synthesis Based On A Modified Koser Reagent

A new metal-free method for the rapid and productive preparation of indoles has been developed. This process is based on sterically congested hypervalent iodine compounds of the family of Koser reagents, and iodosobenzene in combination with 2,4,5-tris-isopropylbenzene sulfonic acid provides the highest yields and fastest reaction times. This reagent alone promotes the chemoselective oxidative cyclization of 2-amino styrenes to indoles in high yields under mild conditions.

Oxidative Diamination Promoted by Dinuclear Iodine(III) Reagents

New dinuclear iodine(III) reagents for the intermolecular diamination of alkenes are reported. These are accessible through protolytic aminolysis events, which generate defined imido-iodine(III) groups.

Synthesis of Benzamides Related to Anacardic Acid and Their Histone Acetyltransferase (HAT) Inhibitory Activities

A group of benzamides related to anacardic acid amide CTPB with alkyl chains of defined length were prepared by a five‐step sequence starting from 2,6‐dihydroxybenzoic acid, and their activities were compared with those reported for the HAT inhibitor anacardic acid (AA). The subset of 4‐cyano‐3‐trifluoromethylphenylbenzamides with shorter chains exhibited activities similar to that of AA, as they behaved as human p300 inhibitors, induced a decrease in histone acetylation levels in immortalized HEK cells, and counteracted the action of the HDAC inhibitor SAHA in MCF7 breast cancer cells. Moreover, an analogue with the shortest alkyl chain induced significant apoptosis at 50 μM in U937 leukemia cells.

Machines vs Malaria: A Flow-Based Preparation of the Drug Candidate OZ439

An efficient preparation of the antimalarial drug candidate OZ439, which was obtained by integrating a machine-assisted approach with batch processes, is reported. This approach allows a rapid and cost-effective production of the key intermediates that were readily elaborated into the target molecule.

Competing Thermal Electrocyclic Ring-Closure Reactions of (2Z)-Hexa-2,4,5-trienals and Their Schiff Bases. Structural, Kinetic, and Computational Studies†

The electrocyclic ring closure reactions of (2Z)-hexa-2,4,5-trienals (vinylallenals) to alkylidene-2H-pyrans and of the corresponding Schiff base derivatives to alkylidenepyridines can be concurrent. Rates of vinylallenal cyclization and imine formation upon addition of n-butylamine determine the extent of the competition. The activation energies for the electrocyclization of a series of 6-substituted-(2Z)-4-tert-butyl-3-methylhexa-2,4,5-trienals 2 and trienimines 4 depend on the steric interactions between the substituents at C6 and the tert-butyl group at C4. Mixtures of alkylidene-2H-pyrans 3 and alkylidenepyridines 5 are obtained with bulky groups at C6, whereas only the latter is obtained with a C6-t-Bu and only the former with substituents of moderate size at C6. The reaction rates were indirectly derived from the empirical observations using a global optimization study based on differential evolution. The cyclizations are torquoselective, and the kinetically favored (E)-alkylidene heterocycles evolve by electrocyclic ring opening/ring closure toward the thermodynamic Z isomers upon extended reaction times. Density functional theory (DFT) calculations of the electrocyclizations helped in their characterization as monorotatory processes with pseudopericyclic features and made it possible to rationalize the reactivity trends and the torquoselectivity.

New Anacardic Acid-Inspired Benzamides: Histone Lysine Acetyltransferase Activators

A series of N‐(4‐cyano‐3‐trifluoromethyl‐phenyl)‐2‐ethoxy‐6‐alkyl (and alkenyl) benzamides related to the anacardic acid derivative CTPB have been prepared from 2,6‐dihydroxybenzoic acid with a Suzuki coupling and addition of the anion of 4‐cyano‐3‐trifluoromethylphenylamine to a benzodioxinone as the key steps. In U937 cells, these analogues, in particular 7 c, 7 d, 7 f and 7 j, induced cell‐cycle arrest in the G1 phase, caused apoptosis in about 20 % of the cells, and increased the acetylation levels of H3. These activities correlate with the enzymatic activation of histone lysine acetyltransferases (KATs): CBP and PCAF.

Hypervalent Iodine Mediated Oxidative Amination of Allenes

An oxidative amination of allenes using a single hypervalent iodine reagent is reported. The reaction proceeds very efficiently for monosubstituted allenes and leads to formation of the corresponding propargylic amines, either as the internal or as the terminal amine. The respective reaction outcome could be influenced in favor of the former product by addition of triphenylphosphine oxide to the iodine(III) reagent.

A facile and green route to terpene derived acrylate and methacrylate monomers and simple free radical polymerisation to yield new renewable polymers and coatings

We present new acrylic monomers derived directly from abundant naturally available terpenes via a facile, green and catalytic approach. These monomers can be polymerised to create new polymers with a wide range of mechanical properties that positions them ideally for application across the commodity and specialty plastics landscape; from packaging, cosmetic and medical, through to composites and coatings. We demonstrate their utility through formation of novel renewable polymer coatings.