Jaume Farràs

Cleavage of tert-butyldimethylsilyl ethers by chloride ion

A general method for the selective cleavage of tert-butyldimethylsilyl ethers in the presence of tert-butyldiphenylsilyl ones has been established using a combination of H2O and a concentrated solution of LiCl in DMF at 90 °C. Since no acids, bases, reducing or oxidizing agents are used, the method seems to be very appropiate for the deprotection of TBDMS ethers in the presence of other sensitive functional groups.

β3-Amino acids by nucleophilic ring-opening of N-nosyl aziridines

Abstract N -Nosyl aziridines can be easily prepared from 1,2-amino alcohols derived from α-amino acids. Nucleophilic ring-opening of N -nosyl aziridines with cyanide ions followed by hydrolysis of the corresponding nitriles lead to N -nosyl β 3 -amino acids, which can be readily converted into a variety of derivatives bearing adequate functionality for peptide synthesis. The proposed methodology is simple, efficient, and amenable to large-scale preparations.

Catalytic C–H Activation of Phenylethylamines or Benzylamines and Their Annulation with Allenes

Tetrahydro-3-benzazepines and tetrahydroisoquinolines are synthesized in one step from allenes and phenylethylamines or benzylamines, respectively. Mechanistically, it is assumed that activation of a C-H bond of an aromatic ring with Pd(II) occurs, directed by the primary amine, leading to the formation of a palladacycle into which an allene then undergoes insertion. The resulting π-allyl intermediate cyclizes to the products by an intramolecular allylic alkylation. The process is particularly useful with 2,3-butadienoates and amines having a quaternary carbon at the α-position.

Allylic alcohols of unexpected configuration by oxazaborolidine-catalysed reduction of α,β-unsaturated ketones. An explanation based on MO calculations

Abstract While the reduction of most α,β-unsaturated ketones with BH 3 :SMe 2 in the presence of ( R )- B -methyl-4,5,5-triphenyl-1,3,2-oxazaborolidine [(R)- 2 ] affords allylic alcohols of the S configuration, that of α,β-unsaturated ketones branched at both the α and α′ positions gives alcohols of the R configuration. Theoretical calculations on complexes of representative enones with BH 3 (6–31G ∗ ) or with BH 3 :(R)- 2 (AM1) may account for the apparent changes in the steric requirements on either side of the CO group.

Pseudoaxially Disubstituted Cyclo-β3-tetrapeptide Scaffolds

Abstract An N,N-disubstituted cyclo-β3-tetrapeptide, identified as a potential molecular scaffold, has been synthesised on a multigram scale from β-homophenylalanine by employing a nosylate-based protection strategy. C2-Symmetric derivatives containing pseudoaxial, combinatorially addressable functionalities have been prepared from the parent cyclopeptide.

Total synthesis of entecavir

Entecavir (BMS-200475) was synthesized from 4-trimethylsilyl-3-butyn-2-one and acrolein. The key features of its preparation are: (i) a stereoselective boron-aldol reaction to afford the acyclic carbon skeleton of the methylenecylopentane moiety; (ii) its cyclization by a Cp2TiCl-catalyzed intramolecular radical addition of an epoxide to an alkyne; and (iii) the coupling with a purine derivative by a Mitsunobu reaction.

New bicyclic nucleosides related to 6-azaisocytidine

Ribosidation of azolo-triazines related to 6-azaisocytosine gives fluorescent nucleosides (6a/6b) and/or novel betaine-like nucleosides (7a/7b), depending on the reaction conditions. The structure of 7a (debenzoylated) has been confirmed by X-ray crystallography. By heating in the presence of Me3SiOTf, betaines 7 rearrange to afford first N8-substituted isomers 8 and eventually 6.

Uracil- and thymine-substituted thymidine and uridine derivatives

Abstract The four possible 3′-uracil-1-yl and 3′-thymin-1-yl derivatives of 3′-deoxythymidine and the four analogous derivatives of 2′-deoxyuridine have been synthesised from thymidine and uridine, respectively. Advantages of the 2-(methoxycarbonyl)vinyl group to prevent the formation of anhydronucleosides and of SnCl 2 /PhSH/Et 3 N in relation to H 2 /Pd for the reduction of most azido groups are disclosed.

Design and synthesis of a novel cyclo-β-tetrapeptide

Abstract N -Substituted tetralactams (cyclo-β-tetrapeptides) have been identified as potential molecular scaffolds by computer-aided design; compound 2 , arising from l -β-homophenylalanine, has been prepared as a model system and its structure elucidated by single crystal X-ray analysis and NMR spectroscopy.

4-31G ab initio and MNDO semi-empirical calculations on bicyclic CN7– and N8 species, and n.m.r. and i.r. studies on 15N-labelled CN7–

Hepta-azapentalene anion and octa-azapentalene are predicted by both 4-31G ab initio and MNDO semi-empirical calculations to be true minima on the CN7– and N8 potential hypersurfaces, respectively; 15N scrambling from labelled 5-azidotetrazole anion is shown to occur by 15N n.m.r. and i.r. spectroscopy, all data pointing to the involvement of the bicyclic CN7– intermediate.