Focus on Physico-Chemical Properties of Sulfoximines: Acidity, Basicity and Lipophilicity.

Despite the numerous published syntheses and applications of sulfoximines, very few studies describe their physico-chemical properties and in particular their acidic, basic and lipophilic or hydrophilic characters. We report for the first time the acidity values (pK) of fluorinated sulfoximines in water and in acetonitrile, as well as the basicity (pK) measurements of fluorinated and non-fluorinated sulfoximines in acetonitrile. The same sulfoximine library was also studied in terms of lipophilicity with measurement of the Hansch parameters of the sulfoximine moieties.

Cyclic Sulfoximines as Methyl and Perdeuteromethyl Transfer Agents and Their Applications in Photoredox Catalysis.

Benzo[1,3,2]dithiazole-1,1,3-trioxides are bench-stable and easy-to-use reagents. In photoredox catalysis, they generate methyl and perdeuteromethyl radicals which can add to a variety of radical acceptors, including olefins, acrylamides, quinoxalinones, isocyanides, enol silanes, and N-Ts acrylamide. As byproduct, a salt is formed which can be regenerated to the original methylating agent.

Electrophilic Fluorination of Silyl Dienol Ethers: a General and Selective Access to γ-Fluoro Enals.

We describe the direct synthesis of γ-fluoro enals from the corresponding silyl dienol ethers. This simple process operates under mild conditions and is compatible with a wide range of functionalities. The high γ regioselectivity of this protocol was rationalized by means of theoretical calculations.

The Revival of Enantioselective Perfluoroalkylation - Update of New Synthetic Approaches from 2015-2022.

Over the last years, methods devoted to the synthesis of asymmetric molecules bearing a perfluoroalkylated chain have been limited in number. Among them, only a few can be used on a large variety of scaffolds. This microreview aims at summarizing these recent advances in enantioselective perfluoroalkylation (-CF , -CF H, -C F ) and highlights the need for new enantioselective methods to easily synthesize chiral fluorinated molecules which would be useful for the pharmaceutical and agrochemical industries.

Remote Radical Trifluoromethylation: A Unified Approach to the Selective Synthesis of γ-Trifluoromethyl α,β-Unsaturated Carbonyl Compounds.

Site-selective trifluoromethylation of silyl dienol ethers derived from α,β-unsaturated aldehydes, ketones, and amides was achieved for the first time in the remote γ position. This photoredox catalyzed process is quite general to compounds bearing many functionalities and is applicable to the late-stage functionalization of biorelevant molecules. The use of -perfluoroalkyl sulfoximines as ·R radical sources enables the generalization of the reaction to other perfluoroalkyl groups (R = CFH, CF).

Radical α-Trifluoromethoxylation of Ketones under Batch and Flow Conditions by Means of Organic Photoredox Catalysis.

The first light-driven method for the α-trifluoromethoxylation of ketones is reported. Enol carbonates react with -trifluoromethoxy-4-cyano-pyridinium, using the photoredox catalyst 4-CzIPN under 456 nm irradiation, affording the α-trifluoromethoxy ketones in ≤50% isolated yield and complete chemoselectivity. As shown by 29 examples, the reaction is general and proceeds very rapidly under batch (1 h) and flow conditions (2 min).

Structure and Reactivity of N-Heterocyclic Alkynyl Hypervalent Iodine Reagents.

Ethynylbenziodoxol(on)e (EBX) cyclic hypervalent iodine reagents have become popular reagents for the alkynylation of radicals and nucleophiles, but only offer limited possibilities for further structure and reactivity fine-tuning. Herein, the synthesis of new N-heterocyclic hypervalent iodine reagents with increased structural flexibility based on amide, amidine and sulfoximine scaffolds is reported. Solid-state structures of the reagents are reported and the analysis of the I-C bond lengths allowed assessing the trans-effect of the different substituents.

Direct Trifluoromethylation of Alcohols Using a Hypervalent Iodosulfoximine Reagent.

The direct trifluoromethylation of a variety of aliphatic alcohols using a hypervalent iodosulfoximine reagent afforded the corresponding ethers in moderate to good yields (14-72 %). Primary, secondary, and even tertiary alcohols, including examples derived from natural products, underwent this transformation in the presence of catalytic amounts of zinc bis(triflimide). Typical reaction conditions involved a neat mixture of 6.

Merging hypervalent iodine and sulfoximine chemistry: a new electrophilic trifluoromethylation reagent.

Electrophilic trifluoromethylation is at the forefront of methodologies available for the installation of the CF moiety to organic molecules; research in this field is largely spurred by the availability of stable and accessible trifluoromethylation reagents, of which hypervalent iodine and sulfoximine based compounds have emerged as two prominent reagent classes. Herein, we describe the facile synthesis of an electrophilic trifluoromethylation reagent which merges these two scaffolds in a novel hypervalent iodosulfoximine compound. This presents the first analogue of the well-known Togni reagents which neither compromises stability or reactivity.

Four-Component Photoredox-Mediated Azidoalkoxy-trifluoromethylation of Alkenes.

We report herein an efficient four-component photoredox-catalyzed reaction. Under the optimized conditions using [Ru(bpy)(PF)] as the photocatalyst, a wide range of terminal and internal alkenes can efficiently undergo azidoalkoxy-trifluoromethylation in the presence of Umemoto's reagent, carbonyl compound, and TMSN, giving rise to original and highly complex molecules in a single operation.

Divergent Synthesis of 1,2-Benzo[ e]thiazine and Benzo[ d]thiazole Analogues Containing a S-Trifluoromethyl Sulfoximine Group: Preparation and New Properties of the Adachi Reagent.

We report here the preparation of unprecedented analogues of 1,2-benzothiazine and benzoisothiazole incorporating the S-trifluoromethyl sulfoximine group in their core. Using a stable precursor to start, cyclization occurs via a catalytic controlled process. The choice of the catalyst is crucial for selectivity toward the five- or the six-membered ring.

One-Pot Synthesis of Aryl- and Alkyl S-Perfluoroalkylated NH-Sulfoximines from Sulfides.

A general efficient one-pot synthesis of S-perfluoroalkylated NH-sulfoximines from sulfides has been developed using phenyliodine diacetate (PIDA) and ammonium carbamate. Remarkable rate enhancement with trifluoroethanol was observed, presumably due to H-bonding effects. These mild and metal-free conditions are compatible with -CH F, -CFCl , -CF H, -CF Br, -C F , and -CF groups, in both the alkyl- and aryl series.

Dichlorotrifluoromethoxyacetic Acid: Preparation and Reactivity.

We describe the first gram scale preparation of the reagent dichlorotrifluoromethoxyacetic acid. This stable compound is obtained in five steps starting from the cheap diethylene glycol. The reactivity of the sodium salt of this fluorinated acid was also tested and allowed the preparation of new amides.

Generation of the SCF Radical by Photoredox Catalysis: Intra- and Intermolecular Carbotrifluoromethylthiolation of Alkenes.

We report the first use of N-trifluoromethylthiosaccharin as the source of SCF radical under photoredox catalysis. This allowed an efficient and general visible-light-mediated carbotrifluoromethylthiolation of alkenes. Under the optimized conditions using fac-[Ir(ppy) ] as the photocatalyst, various N-aryl acrylamides as well as a wide range of substituted styrenes can readily be difunctionalized in an intra- or intermolecular fashion, affording the corresponding SCF -containing products in good to excellent yield.

Improvements of TArgeted multiplex mass spectrometry IMaging.

MALDI mass spectrometers have become popular tools for imaging histological sections. Currently this technology is primarily used for imaging naturally occurring molecules. Here we report on the improvement of TArgeted multiplex MS IMaging (TAMSIM) technology.

Correlation between mRNA levels and functional role of alpha1-adrenoceptor subtypes in arteries: evidence of alpha1L as a functional isoform of the alpha1A-adrenoceptor.

The mRNA levels for the three alpha1-adrenoceptor subtypes, alpha1A, alpha1B, and alpha1D, were quantified by real-time RT-PCR in arteries from Wistar rats. The alpha1D-adrenoceptor was prominent in both aorta (79.0%) and mesenteric artery (68.

Pathological role of a constitutively active population of alpha(1D)-adrenoceptors in arteries of spontaneously hypertensive rats.

1. The role of a constitutively active population of alpha(1D)-adrenoceptors was analysed in arteries obtained from spontaneously hypertensive rats (SHR) and controls (WKY) divided into three groups: young prehypertensive, adult hypertensive, and adult animals chronically treated with captopril (50 mg kg(-1) per day orally) in order to prevent the hypertensive state. 2.