Dario Perdicchia

A convenient procedure for the synthesis of tetrathia-[7]-helicene and the selective α-functionalisation of terminal thiophene ring

This paper describes a convenient preparation of tetrathia-[7]-helicene (TH[7]), the generation of the α-anion on the terminal thiophene ring, and the synthesis of the 2-formyl-tetrathia-[7]-helicene (2-CHO-TH[7]). The key intermediate trans-1,2-dibenzodithiophene-ethene, prepared in 97% yield by McMurry coupling of the 2-formyl-benzo[1,2-b;4,3-b′]dithiophene, was transformed into TH[7] using a known procedure. The described method affords TH[7] in 46% overall yield, which is more than four times the yield previously reported in the literature. The α-anion of TH[7], which is easily generated on the α-position of one of the terminal thiophene rings, reacts with electrophilic reagents such as D2O and DMF. The latter reaction proved to be the best way to prepare 2-CHO-TH[7], a key intermediate for the preparation of new substituted heterohelicenes.

Enzymatic Kinetic Resolution of 2-Piperidineethanol for the Enantioselective Targeted and Diversity Oriented Synthesis †

2-Piperidineethanol (1) and its corresponding N-protected aldehyde (2) were used for the synthesis of several natural and synthetic compounds. The existence of a stereocenter at position 2 of the piperidine skeleton and the presence of an easily-functionalized group, such as the alcohol, set 1 as a valuable starting material for enantioselective synthesis. Herein, are presented both synthetic and enzymatic methods for the resolution of the racemic 1, as well as an overview of synthesized natural products starting from the enantiopure 1.

Enantioselective synthesis of (R)-(−)-baclofen using Fischer-type carbene anions

Abstract The antispastic drug ( R )-(−)-baclofen has been synthesized enantioselectively using a diastereoselective Michael addition reaction of the conjugate base of an enantiopure Fischer-type amino carbene to p -chloro-nitrostyrene.

Michael addition of nitromethane to non-racemic chiral Cr(CO)3 complexes of ethyl cinnamate derivatives: stereoselective synthesis of (R)-(−)-baclofen

Abstract We carried out a highly stereoselective Michael addition (96% de ) of nitromethane to enantiomerically pure tricarbonyl(ethyl-4-chloro-2-trimethylsilylcinnamate)chromium(0). This reaction is the key step in the synthesis of ( R )-(−)-baclofen, a potent antispastic drug.

Stereoselective synthesis of β-sultams using chiral tricarbonyl(η6-arene)chromium(0) complexes

Abstract The reaction of (−)1R or (+)-1S-tricarbonyl(2-substituted benzaldehyde)chromium complexes with tertbutylmethanesulfonamide dianion afforded, after decomplexation and intramolecular cyclization, the enantiomerically pure N-tert-butyl-3-(2-phenyl substituted)-1,2-thiazetidine 1,1 dioxide derivatives. The hydrolytic ring opening gave the corresponding enantiopure β-aminosulfonic acid.

The 1,2,3-triazole ring as a bioisostere in medicinal chemistry

1,2,3-Triazole is a well-known scaffold that has a widespread occurrence in different compounds characterized by several bioactivities, such as antimicrobial, antiviral, and antitumor effects. Moreover, the structural features of 1,2,3-triazole enable it to mimic different functional groups, justifying its wide use as a bioisostere for the synthesis of new active molecules. Here, we provide an overview of the 1,2,3-triazole ring as a bioisostere for the design of drug analogs, highlighting relevant recent examples.

A new ‘one-pot’ synthesis of hydrazides by reduction of hydrazones

Abstract A new, high-yielding methodology for reducing hydrazones to hydrazines is described, which allows the synthesis of different mono-, di- and trisubstituted hydrazines. Moreover, the reduction step can be followed by an in situ reaction with a carboxylic acid making possible a ‘one-pot’ synthesis of trisubstituted hydrazides. The method is relatively general and, in principle, suitable for industrial applications.

Synthesis of the first chiral PNA monomer labelled with a Fischer-type carbene complex

Abstract The synthesis, through a cross-metathesis reaction, of the first chiral peptide nucleic acid (PNA) monomer labelled with a Fischer-type carbene complex of chromium is reported. IR analysis of the new bioconjugate shows that the Cr(CO) 4 moiety represents a suitable spectroscopic probe for diagnostic purposes.

Chiral nitrogen-stabilized Fischer carbene complexes: an efficient tool in the stereocontrolled elaboration of additional stereogenic centers*

The elaboration of the organic ligand of amino and hydrazino carbene complexes of the Fischer type through the reactions of their anions with electrophiles is a useful tool for achieving the stereoselective formation of new carbon-carbon bonds. Anions of chiral carbene complexes substituted with a C2 symmetry amine give stereoselective 1,4-Michael additions to nitroolefins, thus achieving a new entry to b-aryl-g-aminobutyric acid derivatives, which are biologically important molecules. Moreover, two new and complementary protocols for the synthesis of alkyl hydrazino carbene complexes have been developed and the first reactions of their conjugated bases with alkyl halides and aldehydes are reported.

Fischer-type alkyl(hydrazino)carbene complexes: new synthetic potential in comparison with aminocarbene complexes

Abstract A general picture is given of the reactivity of the two Fischer-type alkyl(hydrazino)carbene complexes (CO) 5 CrC(CH 3 )N(Bn)N(CH 3 ) 2 ( 1 ) and (CO ) 4 CrC(CH 3 )N(Bn)N (CH 3 ) 2 ( 3 ). Unlike their organic isolobal hydrazide analogues, they easily yield the corresponding α-anions at −78°C, which react with various electrophiles. Furthermore, the tetracarbonyl chelate 3 (easily generated from 1 ) has greater synthetic potential than aminocarbenes: for example, it can be alkylated stepwise twice in the α-position, thus making it possible to introduce a new stereogenic centre in the molecule.