Ethyl dibromofluoroacetate: a versatile reagent for the synthesis of fluorinated molecules

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Synthesis of 3-aryl-2-arylamidobenzofurans based on the Curtius rearrangement

The synthesis of novel 3-aryl-2-arylamidobenzofurans has been accomplished via a Curtius rearrangement strategy in four steps from benzofuran-2-carboxylic acids. The requisite Suzuki-Miyaura cross-coupling, with benzyl 3-bromobenzofuran-2-ylcarbamate or 2-arylamido-3-bromobenzofurans, revealed an unusual reductive debromination process due to the presence of the free NH group. This dehalogenation can be suppressed by N-alkylation. DMAP is an efficient reagent for the one-pot conversion of benzyl benzofuran-2-ylcarbamates into the corresponding benzofuran-2-arylamides through aroylation, thus acting both as an acyl transfer reagent and a deprotecting agent of the Cbz group. A mechanism is postulated.     

Gram-scale synthesis of iejimalide B

Iejimalide B ( 2 ) is the most promising member of a small family of marine polyene macrolides endowed with remarkably selective activity against human cancer cell lines. As this product, however, is hardly available from the natural sources, a detailed evaluation requires the development of an efficient and practical synthetic approach. This challenge has now been met by adapting the first total synthesis of 2 previously reported by our group to the needs of high material throughput. Redesigning the access routes to the five required building blocks in combination with a careful optimization of the fragment coupling processes provided gram amounts of this valuable compound in a sequence of no more than 16 linear steps with an overall yield of about 7 %. Key elements of the successful strategy include: i) three hydrostannylation processes of elaborate terminal alkynes with “lower order” stannyl cuprates, ii) a Brown allylation, a Noyori transfer hydrogenation, and a Marshall propargylation to set the chiral centers at C9, C17, C22 and C23, and iii) a modified Takai–Utimoto olefination for the preparation of the very labile skipped 1,4‐diene flanking the ester group. The assembly process benefited from a particularly mild protocol for the Stille cross‐coupling previously developed in this laboratory, which clearly outperformed the alternative Suzuki reaction in terms of yield and scalability. The 24‐membered macrocyclic frame was forged by a remarkably selective ring‐closing metathesis reaction (RCM), in which two out of the ten double bonds present in the cyclization precursor were selectively activated with the aid of a second‐generation Grubbs catalyst.     

Silica nanoparticles containing a rhodamine dye and multiple gold nanorods

Silica shells are grown around colloidally synthesized gold nanorods (AuNRs) to form core–shell particles (AuNR@SiO₂) of variable occupancy, defined as the number of AuNRs per silica particle. Multiple AuNR occupancy within the silica shell, confirmed with high-resolution electron microscopy, is reflected in a redshift of the longitudinal plasmon mode of the nanorods due to multipolar coupling between AuNRs of a favored end–end orientation. In addition to the plasmon resonance that dominates their absorbance spectra, FL-AuNR@SiO₂, core–shell particles incorporating a lipid probe (rhodamine-DOPE), can be monitored by their fluorescence and Raman signals. Optical and scanning electron microscopy (SEM) images are compared directly, enabling the correlation of spectroscopic characteristics with particle morphology. Raman and SEM images show that the most intense Raman signals come from aggregates of AuNRs trapped within the silica matrix. Biexponential fits to fluorescence decays indicate that competing mechanisms of quenching and fluorescence enhancement contribute to a reduced fluorescence lifetime of rhodamine-DOPE located near the AuNRs.     

Mannich-Type Reactions of Alkylzinc Reagents

Mannich-type reactions involving alkylzinc reagents have been developed using different strategies. We show that the addition of these organometallic species to sulfonyl imines occurs upon simple heating and affords Mannich products in moderate to excellent yields (14 examples, 30–99 %). Interestingly, N-alkyl imines were also found to be suitable partners after activation as an acyliminium by acetyl chloride (12 examples, 49–86 %) or, more originally, by TMSCl (14 examples, 26–87 %). These methods proved complementary, leading to the preparation of both N-protected secondary or tertiary amines and N-unprotected secondary amines in good yields, with an increased eco-compatibility, and under simple conditions.     

Influence of the Crystallinity of Silver Nanoparticles on Their Magnetic Properties

The magnetic properties of noble-metal nanoparticles are a puzzling phenomenon, tentatively often explained as a size effect or a ligand effect. Many experimental studies performed to date have attempted to vary these readily available parameters without reaching a definitive conclusion. In an attempt at better understanding the role of core crystallinity on these magnetic properties, we have compared the behavior of silver nanoparticles, which were either single-crystalline or multi-twinned, of almost identical sizes and with the same ligand coating. Our results indicate that single-crystalline nanoparticles tend to behave as classical paramagnetic materials, whereas multi-twinned ones exhibit a combination of para- and ferro-magnetic behaviors. Our hypothesis is that lattice defects within the core bear magnetic moments which couple through conduction electrons, with dipolar interactions also playing a local and macroscopic role.     

Hyperpolarized 13C NMR Spectroscopy of Urine Samples at Natural Abundance by Quantitative Dissolution Dynamic Nuclear Polarization

Hyperpolarized nuclear magnetic resonance (NMR) offers an ensemble of methods that remarkably address the sensitivity issues of conventional NMR. Dissolution Dynamic Nuclear Polarization (d-DNP) provides a unique and general way to detect ¹³C NMR signals with a sensitivity enhanced by several orders of magnitude. The expanding application scope of d-DNP now encompasses the analysis of complex mixtures at natural ¹³C abundance. However, the application of d-DNP in this area has been limited to metabolite extracts. Here, we report the first d-DNP-enhanced ¹³C NMR analysis of a biofluid -urine- at natural abundance, offering unprecedented resolution and sensitivity for this challenging type of sample. We also show that accurate quantitative information on multiple targeted metabolites can be retrieved through a standard addition procedure.     

Sydnone-Cyanines as Clickable Probes for Fluorescent Labelling

The synthesis of four clickable sydnone-heptamethine cyanine derivatives is described in this article. The synthetic route is based on a palladium-cross coupling reactions of sydnone boronates affording the desired sydnone-cyanine conjugates in only five steps. These compounds were shown to react smoothly with cyclooctynes to form the corresponding pyrazoles clicked products quantitatively at room temperature and with rate constants up to 18 m ⁻¹ ⋅ s⁻¹, affording interesting new tools for biorthogonal fluorescent labelling of (bio)molecules. Fluorescence properties of both sydnone- and pyrazole-cyanines are described, as well.     

Asymmetric Allenylation of Alkynes mediated by Chiral Organoselenated Reagents under Oxidative Conditions

The reactivity of novel chiral lactamide-substituted diselenide-based reagents under oxidative conditions was exploited to develop a metal-free method for the preparation of enantioenriched allenylamides from simple alkynes in good yields, and with enantiomeric excesses up to 99 %. The key of the success in this method is attributed to the hydrogen-bonded lactamide appendages that ensure configurational stability of chiral vinyl selenoxide intermediates for an optimal enantiotopic β-syn-elimination step.