Jean-Marc Weibel

The organic chemistry of silver acetylides

Silver acetylides are among the oldest organometallics known; however, their applications in organic chemistry remained scarce until very recently. Indeed, several reactions involving silver salts as catalyst or silver acetylides have been reported in the past five years. The extreme mildness and very low basicity of these nucleophilic reagents nicely complement the behavior of other alkynyl metals, rendering them very useful in various transformations, especially in the synthesis of complex molecules. Silver acetylides are now seen as promising tools in organic chemistry. This critical review focuses on this emerging field, and, with emphasis on mechanistic aspects, cover the synthesis of silver acetylides, their applications in organic chemistry and reactions involving silver salts as catalysts where silver acetylides are probable intermediates.

Mechanistic Studies and Improvement of Coinage Metal-Catalyzed Transformation of Alkynyloxiranes to Furans: An Alcohol Addition−Cyclization−Elimination Cascade

In the presence of alcohol Ag or Au salts or complexes catalyze the conversion of alkynyloxiranes to substituted furans. Both catalysts are effective, and a large furan diversity can be obtained in high yield with one or the other catalyst. Mechanistic studies revealed that a cascade pathway and not the sometimes reported direct intramolecular nucleophilic addition of oxirane oxygen atom to intermediate acetylene-metal pi-complex occurs. Under the defined conditions, the intermediate formation of epoxide opening products has been identified. Depending on the catalyst, one or both of the latter cyclized to dihydrofurans, and further elimination of the alcohol led to the corresponding furans. These results highlight the duality between oxophilicity and alkynophilicity of Ag or Au salts.

Silver(I)-Catalyzed Cascade: Direct Access to Furans from Alkynyloxiranes

Functionalized furans are conveniently formed by a new silver(I)-catalyzed reaction of alk-1-ynyl oxiranes in the presence of p-toluenesulfonic acid and methanol. Evidence supported a cascade mechanism.

Targeting the dimerization initiation site of HIV-1 RNA with aminoglycosides: from crystal to cell.

The kissing-loop complex that initiates dimerization of genomic RNA is crucial for Human Immunodeficiency Virus Type 1 (HIV-1) replication. We showed that owing to its strong similitude with the bacterial ribosomal A site it can be targeted by aminoglycosides. Here, we present its crystal structure in complex with neamine, ribostamycin, neomycin and lividomycin. These structures explain the specificity for 4,5-disubstituted 2-deoxystreptamine (DOS) derivatives and for subtype A and subtype F kissing-loop complexes, and provide a strong basis for rational drug design. As a consequence of the different topologies of the kissing-loop complex and the A site, these aminoglycosides establish more contacts with HIV-1 RNA than with 16S RNA. Together with biochemical experiments, they showed that while rings I, II and III confer binding specificity, rings IV and V are important for affinity. Binding of neomycin, paromomycin and lividomycin strongly stabilized the kissing-loop complex by bridging the two HIV-1 RNA molecules. Furthermore, in situ footprinting showed that the dimerization initiation site (DIS) of HIV-1 genomic RNA could be targeted by these aminoglycosides in infected cells and virions, demonstrating its accessibility.

Gold(I)-catalyzed cycloisomerization of β-alkynylpropiolactones to substituted α-pyrones.

Substituted α-pyrones were straightforwardly synthesized in good to excellent yields by a new gold(I)-catalyzed rearrangement of β-alkynylpropiolactones.

Gold(I)-catalyzed rearrangement of N-aryl 2-alkynylazetidines to pyrrolo[1,2-a]indoles.

Various N-aryl-2-alkynylazetidines were very efficiently converted to pyrrolo[1,2-a]indoles with gold catalysts, especially the 2-biphenyl-dicyclohexylphosphino-gold(I) hexafluoroantimonate, in dichloromethane at room temperature. Additionally, two formal syntheses of bioactive non-natural compounds, i.e. 7-methoxymitosene and an 5-HT(2C) receptor agonist, have been achieved.

Gold(I)/(III)-catalyzed rearrangement of divinyl ketones and acyloxyalkynyloxiranes into cyclopentenones.

Multifaceted gold(I/III) catalysts with their carbophilic and oxophilic characters catalyzed very efficiently the formation of hydroxylated cyclopentenones from simple divinyl ketones or acyloxyalkynyloxiranes. The Nazarov reaction is rapidly performed in dichloroethane with 5 mol % of the simple gold(III) trichloride salt at 70 °C, while the rearrangement of alkynyloxiranes requires 5 mol % of a more stable NHC gold(III) triflimidate complex.

Dependence of the cellular internalization and transfection efficiency on the structure and physicochemical properties of cationic detergent/DNA/liposomes.

Control of the structure and physicochemical properties of DNA complexed with nonviral vectors is essential for efficient biodistribution and gene delivery to cells. Cationic liposomes interact with DNA giving transfection competent but large and heterogeneous aggregates. On the other hand, cationic detergents condense DNA into small homogeneous but reversible complexes inefficient for transfection.

Silver(I)-catalyzed deprotection of p-methoxybenzyl ethers: a mild and chemoselective method.

The p-methoxybenzyl protecting group (PMB) on various alcohols and an acid was efficiently and selectively cleaved by the action of a catalytic amount of silver(I) hexafluoroantimonate combined with 0.5 equiv of 1,3,5-trimethoxybenzene in dichloromethane at 40 °C.

Silver & gold-catalyzed routes to furans and benzofurans

Silver and gold have become incredibly versatile and mild catalysts for numerous transformations, especially in heterocycle synthesis. For the most prominent of them, i.e. furans, silver and gold, with their unique reactivity and mildness, allow numerous possible routes to highly substituted and/or functionalized furans from a large variety of starting materials. Silver and gold catalysis provide thus the most flexible way to this important family of compounds. The present review describes these silver and gold-catalyzed routes, with some emphasis on mechanistic aspects, and proposes a comparison of both the silver and the gold-catalyzed syntheses of furans.