Silvano Cadamuro

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.

SYNTHESIS, CHARACTERIZATION AND CELL VIABILITY TEST OF SIX VANADYL COMPLEXES WITH ACETYLACETONATE DERIVATIVES

Vanadium compounds are known to display a number of therapeutic effects, namely insulin-mimetic and cardiovascular effects. Evidence of the antiproliferative and proapoptotic activity of a number of vanadyl complexes, together with their low toxicity, establishes these metal compounds as promising antitumoral therapeutic agents. In the present work, we describe the synthesis and full characterization of six new vanadyl complexes with acetylacetonate derivatives bearing asymmetric substitutions on the β-dicarbonyl moiety: the complexes were characterized in the solid state as well as in solution. Our results show that all complexes are in square pyramidal geometry; cis isomers in the equatorial plane are favored in the presence of strongly coordinating solvents. EPR evidence suggests that all complexes are in the bis-chelate form, although in two cases the mono-chelated complex seems to be present as well. Preliminary tests carried out on non-tumor and tumor cell lines show that these complexes are effective in suppressing cell viability and elicit a distinct response of tumor and non-tumor cells.

General methods for synthesizing 2,4-diacylpyrroles and their precursors containing one or two masked acyl groups

A thorough study of the synthesis of 2,4-diacylpyrroles by direct acylation of pyrrole and 2- and 3-acylpyrroles is reported. Among these, Friedel–Crafts acylation of 3-acylpyrroles is the most general and advantageous method because it utilises easily accessible starting materials. In addition it is always regiospecific and readily provides 2,4-diacylpyrroles containing identical or different acyl groups in very high yields (81–100%) under mild conditions. Alternative procedures concern the synthesis of precursors of 2,4-diacylpyrroles containing one or two acyl groups masked by a 1,3-benzodithiolyl or 1,3-benzoxathiolyl group and subsequent hydrolysis with HgO–35% aq. HBF4Me2SO. Overall yields are always good (52–60%). Indirect acylation constitutes a secure complement to direct acylation when it is necessary to operate in the presence of protected acyl groups.

CONVENIENT ROUTE FOR THE SYNTHESIS OF 3-SUBSTITUTED AND 3,4-DISUBSTITUTED PYRROLE-2,5-DICARBALDEHYDES

3-Substituted and 3,4-disubstituted pyrrole-2,5-dicarbaldehydes have been obtained by hydrolysis with HgO–35% aq. HBF4–DMSO of the intermediates 4 and 5 prepared by electrophilic substitution reactions on 2,5-bis(1,3-benzodithiol-2-yl)pyrrole. The overall yields starting from pyrrole ranged from 41–88%.

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.

A convenient general method for the synthesis of pyrrole-2,5-dicarbaldehydes

A new general method for the synthesis of pyrrole-2,5-dicarbaldehyde and its 3-mono- and 3,4-disubstituted derivatives is reported. It involves the intermediate formation of the corresponding 2,5-bis(1,3-benzodithiol-2-yl)pyrroles followed by hydrolysis with HgO–35% aq. HBF4–DMSO. Pyrrole-2,5-dicarbaldehyde was obtained in overall yields of 43–65%, whilst that of the derivatives was 32–90%. Moreover the methylation of the corresponding dithiolic intermediate with further hydrolysis resulted in the formation of 1-methylpyrrole-2,5-dicarbaldehyde in 90% overall yield.