Post-Transition-State Dynamic Effects in the Transmetalation of Pd(II)-F to Pd(II)-CF.

The observation of post-transition-state dynamic effects in the context of metal-based transformation is rare. To date, there has been no reported case of a dynamic effect for the widely employed class of palladium-mediated coupling reactions. We performed an experimental and computational study of the trifluoromethylation of PdF, which is a key step in the Pd/Pd-catalyzed trifluoromethylation of aryl halides or acid fluorides.

Access to N-CF Formamides by Reduction of N-CF Carbamoyl Fluorides.

The departure into unknown chemical space is essential for the discovery of new properties and function. We herein report the first synthetic access to N-trifluoromethylated formamides. The method involves the reduction of bench-stable NCF carbamoyl fluorides and is characterized by operational simplicity and mildness, tolerating a broad range of functional groups as well as stereocenters.

Access to Cyclic -Trifluoromethyl Ureas through Photocatalytic Activation of Carbamoyl Azides.

We report the mild activation of carbamoyl azides to the corresponding nitrenes using a blue light/[Ir]-catalyzed strategy, which enables stereospecific access to -trifluoromethyl imidazolidinones and benzimidazolones. These novel structural motifs proved to be highly robust, allowing their downstream diversification. On the basis of our combined computational and experimental studies, we propose that an electron rebound with the excited metal catalyst is undergone, involving a reduction-triggered nitrogen loss, followed by oxidation to the corresponding carbamoyl nitrene and subsequent C-H insertion.

Recent progress in asymmetric synergistic catalysis - the judicious combination of selected chiral aminocatalysts with achiral metal catalysts.

In this review we survey recent synergistic applications of a chiral organocatalyst with an achiral metal to perform stereoselective transformations of synthetic utility (since 2016). The transformations are classified by the modes of reactivity deployed, focussing on organocatalytic activation of carbonyl substrates as chiral nucleophiles the α-position (, as enamines) and as chiral electrophiles the β-position (, as iminium ions) combined with complementary activation of their reaction partners by an achiral metal co-catalyst (, Pd or Cu-based). Corresponding radical reactions are also presented in which photocatalysis mediated by achiral metal complexes replaces the metal co-catalyst.

Synthesis of -CF Alkynamides and Derivatives Enabled by Ni-Catalyzed Alkynylation of -CF Carbamoyl Fluorides.

The expansion of chemical space associated with ubiquitous motifs is key to unleash new properties and functions. In this context, alkynamides, prevalent in numerous drugs and materials, represent an untapped resource. We herein report the first synthetic access to -trifluoromethyl alkynamides.

Understanding the Diastereopreference of Intermediates in Aminocatalysis: Application to the Chiral Resolution of Lactols.

Downstream intermediates are crucial for the reactivity and selectivity of aminocatalytic reactions. We present an analysis of the stereopreference in aminocatalytic downstream intermediates, which reveals an inconspicuous mechanism of chiral recognition between the catalyst and the rest of the molecule. We delineate a stereoelectronic model to rationalize the mode of chiral transmission.

Illuminating the Path to Target GPCR Structures and Functions.

G-Protein-coupled receptors (GPCRs) are ubiquitous within eukaryotes, responsible for a wide array of physiological and pathological processes. Indeed, the fact that they are the most drugged target in the human genome is indicative of their importance. Despite the clear interest in GPCRs, most information regarding their activity has been so far obtained by analyzing the response from a "bulk medium".

Hydroarylation of Alkenes by Protonation/Friedel-Crafts Trapping: HFIP-Mediated Access to Per-aryl Quaternary Stereocenters.

Upon treatment with a combination of HFIP and an organic sulfonic acid, alkenes behave as Brønsted bases and protonate to give carbocations which can be trapped by electron-rich arenes. The reaction constitutes a Friedel-Crafts hydroarylation which proceeds with Markovnikov selectivity and is orthogonal to traditional metal-catalyzed processes. Intermolecular transfer hydrogenation and hydrothiolation under analogous conditions are also demonstrated.

Visual kinetic analysis.

Visual kinetic analyses extract meaningful mechanistic information from experimental data using the naked-eye comparison of appropriately modified progress reaction profiles. Basic kinetic information is obtained easily and quickly from just a few experiments. Therefore, these methods are valuable tools for all chemists working in process chemistry, synthesis or catalysis with an interest in mechanistic studies.

Reversibility and reactivity in an acid catalyzed cyclocondensation to give furanochromanes - a reaction at the 'oxonium-Prins' '-quinone methide cycloaddition' mechanistic nexus.

Herein we report a combined experimental and computational investigation of the acid catalyzed cyclocondensation reaction between styrenyl homoallylic alcohols and salicylaldehyde to form furanochromanes. We disclose a previously unreported isomerisation of the 'unnatural' -fused products to the diastereomeric 'natural' -fused congeners. Notwithstanding the appeal of assuming this corresponds to to isomerisation of Diels-Alder (D-A) adducts concerted retro-cycloaddition/cycloaddition reactions of an generated -quinone methide with the styrenyl alkene, our combined Hammett/DFT study reveals a stepwise Prins-like process discrete benzylic carbocation intermediates for all but the most electron deficient styrenes.