Philippe A. Peixoto

Asymmetric Hydroxylative Phenol Dearomatization Promoted by Chiral Binaphthylic and Biphenylic Iodanes

The long-standing quest for chiral hypervalent organoiodine compounds (i.e., iodanes) as metal-free reagents for asymmetric synthesis continues. Although remarkable progress has recently been made in organoiodine-catalyzed reactions using a terminal oxidant in stoichiometric amounts, there is still a significant need for flaskable chiral iodane reagents. Herein, we describe the synthesis of new iodobinaphthyls and iodobiphenyls, their successful and selective DMDO-mediated oxidation into either λ(3)- or λ(5)-iodanes, and the evaluation of their capacity to promote asymmetric hydroxylative phenol dearomatization (HPD) reactions. Most notably, a C2-symmetrical biphenylic λ(5)-iodane promoted the HPD-induced conversion of the monoterpene thymol into the corresponding ortho-quinol-based [4+2] cyclodimer (i.e., bis(thymol)) with enantiomeric excesses of up to 94%.

Design and Synthesis of Epicocconone Analogues with Improved Fluorescence Properties

Epicocconone is a natural latent fluorophore that is widely used in biotechnology because of its large Stokes shift and lack of fluorescence in its unconjugated state. However, the low photostability and quantum yields of epicocconone have limited its wider use, and in the absence of a total synthesis, this limitation has been a long-standing problem. Here we report a general strategy for the synthesis of epicocconone analogues that relies on a 2-iodoxybenzoic acid-mediated dearomatization and on the replacement of the triene tail of the natural product by an aromatic ring. This design element is general and the synthesis is straightforward, providing ready access to libraries of polyfunctional fluorophores with long Stokes shifts based on the epicocconone core. Our structural modifications resulted in analogues with increased photostability and quantum yields compared with the natural product. Staining proteomic gels with these new analogues showed significant lowering of the detection limit and a 30% increase in the number of low-abundance proteins detected. These epiccoconone analogues will substantially improve the discovery rate of biomarker needles in the proteomic haystack.

Phenol Dearomatization with Hypervalent Iodine Reagents.

This chapter highlights recent developments in phenol dearomatization using organoiodane reagents and a selection of applications in natural product synthesis.

Asymmetric Alkynylation of β-Ketoesters and Naphthols Promoted by New Chiral Biphenylic Iodanes

The preparation of new chiral biphenylic λ3 -iodane reagents bearing transferable alkynyl ligands is described. These reagents transfer their carbon-based ligands onto β-ketoesters with an enantiomeric excess (ee) up to 68u2009%, and most remarkably, enable the dearomative alkynylation of naphthols in good to high yields up to 84u2009%u2009ee.

Epicocconone–Hemicyanine Hybrids: Near Infrared Fluorophores for Protein Staining and Cell Imaging

The development of new near infrared (NIR) dyes is crucial for diverse applications and especially bioimaging, as they absorb and emit light in the therapeutic window (650-950u2005nm). We report here a new family of NIR fluorophores that has been obtained by hybridising hemicyanines with epicocconone. Emission wavelengths of these hybrid dyes is in the range 715-795u2005nm and is combined with large Stokes shifts (75-95u2005nm). The absorption and emission wavelength can be modulated according to the hemicyanine moiety and adding sulfonic acid moieties enhances water solubility. We demonstrate their application in the sensitive detection of proteins in gel electrophoresis and the staining of specific cellular organelles in confocal microscopy. These results are particularly encouraging and bring forward a new fluorescent skeleton for chemical biology.

Metal-free aerobic C–H oxidation of cyclic enones

A metal-free procedure is described for the aerobic and complete C–H methylene oxidation of Hajos–Parrish enones to versatile dihydroindenediones. The synthetic utility of these substrates was illustrated by converting them into highly substituted indanes after an intramolecular Friedel–Crafts conjugate addition. Importantly, the aerobic oxidation was compatible with substrates sensitive to radicals.

Bioinspired Total Synthesis of (−)-Vescalin: A Nonahydroxytriphenoylated C-Glucosidic Ellagitannin

The first total synthesis of the 2,3,5-O-(S,R)-nonahydroxytriphenoylated (NHTP) C-glucosidic ellagitannin (-)-vescalin was accomplished through a series of transformations mimicking the sequence of events leading to its biogenesis. The key steps of this synthesis encompass a Wittig-mediated ring opening of a glucopyranosic hemiacetal, a C-glucosidation event through a phenolic aldol-type reaction, and a Wynberg-Feringa-Yamada-type oxidative phenolic coupling, which forged the NHTP unit of (-)-vescalin.