Margherita Barbero

Chiral derivatives of 1,2-benzenedisulfonimide as efficient Brønsted acid catalysts in the Strecker reaction

Two chiral derivatives of 1,2-benzenedisulfonimide, namely 4-methyl-3,6-bis(o-tolyl)-1,2-benzenedisulfonimide and 4,5-dimethyl-3,6-bis(o-tolyl)-1,2-benzenedisulfonimide, have been easily synthesized in good overall yields (respectively 34% and 41%) by means of an eleven-step synthetic protocol from commercially available 2-methyl-6-nitroaniline or 2,3-dimethyl-6-nitroaniline. 4,5-Dimethyl-3,6-bis(1-naphthyl)-1,2-benzenedisulfonimide was also synthesized, but the overall yield from 2,3-dimethyl-6-nitroaniline was lower (9%). The atropisomers of these compounds have been resolved and (-)atropisomers have been demonstrated to be efficient chiral catalysts in the Strecker reaction.

Preparation and Characterization of Aryl or Heteroaryl(3-indolyl)methylium o-Benzenedisulfonimides

An initial study has been accomplished into the synthetic feasibility of the preparation of diarylcarbenium salt via the direct coupling of aryl (or heteroaryl) aldehydes and arenes (or heteroaryl analogues) in the presence of a strong organic Brønsted acid. A number of stabilized aryl or heteroaryl(3-indolyl)carbenium ions, never previously prepared in the solid state, have been isolated in excellent yields as highly stable o-benzenedisulfonimide salts and have been fully characterized. Their purity has been proven by spectroscopic methods and chemical reduction with NaBH(4). An X-ray crystal structure analysis has been performed on one of the products: an azafulvenium species was shown to be the exclusive structure in the solid state.

A Brønsted acid catalysed enantioselective Biginelli reaction

A chiral derivative of 1,2-benzenedisulfonimide, namely (−)-4,5-dimethyl-3,6-bis(o-tolyl)-1,2-benzenedisulfonimide is herein proven to be an efficient chiral catalyst in a one pot three-component Biginelli reaction. In fact the yields of the target dihydropyrimidines were very high (25 examples; average 91%) and enantiomeric excesses were always excellent (14 examples; average 97%). Ultimately, we herein propose a procedure that displays a number of benefits and advantages including the total absence of solvents, mild reaction conditions, relatively short reaction times and stoichiometric reagent ratios. Target dihydropyrimidines are obtained in adequate purity, making further chromatographic purification unnecessary. Moreover, the chiral catalyst was easily recovered from the reaction mixture and reused, without the loss of catalytic activity.

O-Benzenedisulfonimide as a Reusable Brønsted Acid Catalyst for Hetero-Michael Reactions

Abstract The hetero-Michael reactions among various oxygen, sulfur, and nitrogen nucleophiles and α,β-unsaturated compounds were carried out in the presence of catalytic amounts of o-benzenedisulfonimide as Brønsted acid organocatalyst. The reaction conditions were very mild, and the yields of target products were good. The catalyst was easily recovered and purified, ready to be used in further reactions. This ability grants economic and ecological advantages. Supplemental materials are available for this article. Go to the publishers online edition of Synthetic Communications® to view the free supplemental file. GRAPHICAL ABSTRACT

Synthesis of bench-stable diarylmethylium tetrafluoroborates.

A representative number of bench-stable nonsymmetric diarylcarbenium tetrafluoroborates have been isolated via the direct coupling of aryl (or heteroaryl) aldehydes and N-heteroarenes and fully characterized. They have proven to be highly stable in the presence of both EDG and EWG substituents. An (E)-iminium vinylogous substructure has been shown as the common cation scaffold by X-ray analysis and by NOE determination.

Convenient procedure for converting 1,3-dithiolane-2-thiones into 1,3-dithiolan-2-ones

1,3-Dithiolan-2-ones have been obtained by reaction of 1,3-dithiolane-2-thiones and epoxides in the presence of HBF4·Et2O. The reactions, carried out in anhydrous CH2CL2 at 0–5 °C→room temperature (Procedure A) or in anhydrous chlorobenzene at 0–5-→80 °C (Procedure B), gave product yields of 63–95%. By Procedure B it was also possible to isolate the intermediates 1-oxa-4,6,9-trithiaspiro[4.4]nonanes in good yields (66–85%). Reaction pathways are proposed.

Fungal Anticancer Metabolites: Synthesis Towards Drug Discovery

BACKGROUND Fungi are a well-known and valuable source of compounds of therapeutic relevance, in particular of novel anticancer compounds. Although seldom obtainable through isolation from the natural source, the total organic synthesis still remains one of the most efficient alternatives to resupply them. Furthermore, natural product total synthesis is a valuable tool not only for discovery of new complex biologically active compounds but also for the development of innovative methodologies in enantioselective organic synthesis. METHODS We undertook an in-depth literature searching by using chemical bibliographic databases (SciFinder, Reaxys) in order to have a comprehensive insight into the wide research field. The literature has been then screened, refining the obtained results by subject terms focused on both biological activity and innovative synthetic procedures. RESULTS The literature on fungal metabolites has been recently reviewed and these publications have been used as a base from which we consider the synthetic feasibility of the most promising compounds, in terms of anticancer properties and drug development. In this paper, compounds are classified according to their chemical structure. CONCLUSION This review summarizes the anticancer potential of fungal metabolites, highlighting the role of total synthesis outlining the feasibility of innovative synthetic procedures that facilitate the development of fungal metabolites into drugs that may become a real future perspective. To our knowledge, this review is the first effort to deal with the total synthesis of these active fungi metabolites and demonstrates that total chemical synthesis is a fruitful means of yielding fungal derivatives as aided by recent technological and innovative advancements.

A General Procedure to Selectively Prepare N-Alkylanilines by an Unexpected Reaction of (Z)-(tert-Butylsulfanyl)(aryl)diazenes with Alkyllithium Reagents

A general procedure has been set up to prepare, selectively, the N-monoalkylanilines 7, reacting (Z)-(tert-butylsulfanyl)(aryl)diazenes 3 with alkyllithium 6 (MeLi, BuLi, s-BuLi, n-C 6 H 1 3 Li). The reactions were carried out in anhydrous diethyl ether at 0 °C or -78 °C, depending on the reagent 6, and then at room temperature. In optimal conditions the yields of the pure products 7 (uncontaminated by dialkylation products) were from good to excellent: for 38 considered examples, 34 were positive with yields varying between 61% and 91% (average yield 78%). Collateral proofs were carried out to support a hypothesized reaction mechanism.

Synthetic application of lithiated tris(methylthio)methane: preparation of aliphatic methyl thiolcarboxylates from the corresponding halides. Convenient synthesis of tris(methylthio)methane

A thorough study directed towards the synthesis of methyl thiolcarboxylates was made on the basis of the following steps: (i) conversion of alkyl halides into the corresponding trimethyl trithioorthocarboxylates by using tris(methylthio)methyllithium in THF at –78 °C; (ii) selective hydrolysis of the intermediates to methyl thiolcarboxylates by using 35% aq. HBF4 in DMSO or, in some cases, in THF. The overall yields of the two stages are, usually, between 70 and 88%. By this procedure it is also possible to incorporate 8O in the carbonyl group of thiol esters (∼98% isotopic purity). Furthermore, a new, convenient method for the preparation of tris(methylthio)methane as the precursor of tris(methylthio)methyllithium was developed.