Hassen Amri

A short large scale synthesis of (±) sarkomycin esters

Abstract : (k) Sarkomycin ethyl ester has been prepared in four steps from ethyl actylate. We have previously described the substitution of a-functionnal acrylic esters by Grignard reagents in the presence of a catalytic amount of copper (I) (1). This reaction can be applied to lithium enolates (ester or ketone). It gives then rise to new a-substituted functional actylates which are of great interest for the synthesis of biological active compounds (a-methylene &valerolactone, (+)-sarkomycin). CH,OAc flc”” =(COOEt FOOEt v 2.5% Cu(l), -7O”C, THF-Et20 - CH20Ac + COOEt Li-CH,-COOt-Bu THF-Et20, -80°C -CH2 Yield 83% COOEt ===c CH,-CH,-COO,-BU 1 Yield 66% A recent publication (2) on the synthesis of (+) sarkomycin including the same phosphonate 3 as a key intermediate prompts us to describe here our results. Many other preparations of (k) sarkomycm (or its esters) have been reported by mutli step syntheses (2, 3) with low overall yields. We report here a very short, large scale and improved synthesls of two (&) sarkomycin esters using low cost products and methodology. a-Methylene glutaric acid diester 1 can be included in a very short

A one pot synthesis of (E)-4-alkylidene-2-cyclohexen-1-ones

Abstract A one pot synthesis of (E)-4-alkylidene-2-cyclohexen-1-ones 2 via a cross coupling of 2-(1-acetoxy alkyl) enones 1 and aliphatic 1,3-diketones in the presence of anhydrous potassium carbonate in absolute ethanol at reflux, is reported.

A total stereospecific route to α-alkylidene-γ-lactams

Abstract A new efficient γ-lactams 4 synthesis was achieved by two successive reactions: alkylation of nitroalkane anions with dimethyl α-(bromomethyl) fumarate 1 leading to the formation of (E)-1-alkyl-2,3-dimethoxycarbonyl butadienes 3a,b resulting of tandem alkylation–elimination (dehydronitration) processes, followed by an intramolecular cyclization on addition of primary amine.

Synthesis, structure and complexing properties of new calix[4](aza)crowns

The synthesis of calix[4](aza)crowns capped by one ‘tren’ or doubly capped by two azacrowns is described. The crystal structure of the tripodal ‘tren’ is given. Complexing properties towards Co2+, Ni2+, Zn2+ and Cu2+ are described. Conclusions are drawn on the role of functional groups and molecular topology in the complexation behavior of calix[4](aza)crowns.

Addition of bromine to β'-(functional alkyl) α, β-unsaturated esters stereoselective synthesis of β-haloderivatives

Abstract A new convenient stereoselective synthesis of β-brominated β′-(functional alkyl) α,β-unsaturated esters has been developed by the reaction of tetraalkylammonium fluoride in HMPA with ethyl 2,3-dibromo 2-(functional alkyl) propionates which can be easily prepared by addition of bromine to β′-(functional alkyl) acrylates. An interpretation of the observed stereoselectivity is proposed.

A Convenient Synthesis of α-Functional Alkyl Vinyl Ketones

Abstract Reaction of 2-functional alkyl-1,3-diketones with 30% aqueous formaldehyde using aqueous 6-10M potassium carbonate solution as base, afforded a-functional alkyl vinyl ketones in good yields.

Nouvelle synthèse d′α-(1-hydroxy)alkyl-β-lactames

Abstract Direct condensation of primary amines and ethyl-2-hydroxyalkylacrylates, in methanol at reflux, gave 3-hydroxyalkylazetidin-2-ones in good to fair yields.

Addition conjuguée d'amines primaires aux composés acryliques α-(1-hydroxy)alkylés : Nouvelles synthèses de β-et de γ-lactames polyfonctionnels

Absract Direct condensation, in methanol, of primary amines on ethyl-α-(1 -hydroxyalkyl)acrylates and 2-(1-carbethoxy-1-hydroxyethyl)acrylonitrile yielded respectively to α-(1-hydroxyalkyl)-β-lactames and α,β-difunctionalized γ-lactames in good to fair yields. In the latter case, reaction with N,N-dialkylated hydrazines gave perhydro-1,2-pyridazinones.

Synthèse de γ-lactames et de perhydro-1,2-pyridazin-3-ones polyfonctionnels

Abstract Direct condensation, in methanol, of primary amines on 2-(1-carbethoxy-1- hydroxyethyl)acrylonitrile yielded to α and β-functionalized γ-lactames 6(a–f) . The same reaction with hydrazines gave perhydro-1,2-pyridazin-3-ones 7 and 8 when nitrogen is not dialkylated.

Copper(I) mediated highly diastereoselective conjugate addition of Grignard reagents to functionalised cycloalkenols: a general and efficient route for the stereoselective synthesis of 5- and 6-membered ring trisubstituted cycloalkanols

Abstract The conjugate addition of magnesium cuprates to various 2-silyloxycyclopentene and 2-silyloxycyclohexene carboxylates leads diastereoselectively to related syn–anti cyclopentanols and cyclohexanols in fair overall yields. The β-elimination occurring with free hydroxylic derivatives is also partially or totally avoided by concomitant in situ trapping of the generated enolates. Attempts to rationalise our results are discussed.