Achille Barco

Diastereoselective synthesis of β-amino-α-hydroxy phosphonates via oxazaborolidine catalyzed reduction of β-phthalimido-α-keto phosphonates

Abstract Reduction of β-phthalimido-α-keto phosphonates, obtained through an Arbuzov reaction between the appropriate acid chloride and triethyl phosphite, with boranes and oxazaborolidine as catalyst, afforded β-phthalimido-α-hydroxy phosphonates in good yields and high diastereoselectivity. Deprotection of the amino group gave the title compounds.

A unified asymmetric approach to substituted hexahydroazepine and 7-azabicyclo[2.2.1]heptane ring systems from D(−)-quinic acid: Application to the formal synthesis of (−)-balanol and (−)-epibatidine

3,4-O-Isopropylidene-3(R),4(S)-dihydroxycyclohexanone 7, a chiron easily prepared through a five step sequence from D(-)-quinic acid 1, has been efficiently utilized as the starting building block for the enantioselective syntheses of (3R,4S)-N-p-toluenesulfonyl-3,4-epoxy-hexahydroazepine 17 and (1R,4S)-N-tert-butoxycarbonyl-7-azabicyclo[2.2.1]heptan-2-one 43, advanced intermediates already taken to (-)-balanol and (-)-epibatidine respectively. While the nitrogen atom ring-insertion via Beckmann rearrangement was the key step for the construction of the hexahydroazepine ring of 17, a regio- and stereospecific intramolecular nucleophilic ring opening of an intermediate cyclic sulfate featured the approach to the substituted 7-azabicyclo[2.2.1]heptane nucleus of 43.

Tandem michael reactions for the construction of pyrrolidine and piperidine ring systems

Abstract A convergent one-pot construction of disubstituted pyrrolidine and piperidine frameworks has been accomplished through a simple protocol involving intermolecular conjugate addition of a nitrogen nucleophile to an electrophilic olefin followed by intramolecular trapping of the generated enolate by a built-in α,β,-unsaturated acceptor.

Synthetic studies towards forskolin

Abstract A model tricyclic system incorporating the complete array of oxygenated functions of the AB portion of forskolin has been synthetized. The highly substituted decalin unit of the natural target has been in turn assembled in a convenient way utilizing an intramolecular nitrile oxide cycloaddition reaction as key step.

Polymer-bound 4-benzylsulfonyl-1-triphenylphosphoranylidene-2-butanone as a tool for the solid-phase synthesis of substituted piperidin-4-one derivatives.

Abstract An efficient method for the construction of 2-substituted-piperidin-4-one derivatives on solid support has been developed using polymer-bound 4-benzylsulfonyl-1-triphenylphosphoranylidene-2-butanone as a convenient precursor for substituted divinyl ketones in the heterocyclization reaction with amines. The resin was released in a recyclable sulfinate form.

Enantioselective synthesis of (+)- and (−)-α-allokainic acid

Abstract A concise enantioselective route to (+)- and (−)-a-allokainic acid from D- and L-serine respectively has been established by enantio- and diastereo-selective tandem Michael reaction methodology for the construction of three chiral centers in a single stage.

Enantioselective approach to 7-azabicyclo[2.2.1]heptane ring systems using D-(−)-quinic acid as the chiral educt: Application to the formal synthesis of (+)-epibatidine

By utilizing D-(−)-quinic acid as the chiral starting material the optically pure 7-[(1,1-dimethylethoxy)carbonyl]-7-azabicyclo[2.2.1.]heptan-2-one 2, an advanced intermediate already taken to (+)-epibatidine 1, a non-opioid analgesic isolated from Ecuadorian poison frogs, was synthetized through a facile, regioselective intramolecular nucleophilic ring opening of a cyclic sulfate moiety.

Generation and cycloaddition reactions of 3-substituted-2-nitro-1,3-dienes

Abstract Two procedures for the regiospecific preparation of 3-substituted-2-nitro-1,3-dienes have been developed. The cycloaddition chemistry of the in situ generated dienes has been investigated.

Enantiodivergent synthesis of 2-hydroxymethyl-3-hydroxy-4-nitro-pyrrolidines through tandem Michael-Henry reaction using L-serine as the chiral educt

Abstract By utilizing L-serine, both enantiomers of all trans 2-hydroxymethyl-3-hydroxy-4-nitro-pyrrolidine were efficiently prepared through tandem Michael-Henry methodology. Their stereochemistry has been assigned through conversion of one of them to trans 2-hydroxymethyl-3-hydroxypyrrolidine, a naturally occurring compound recently isolated from Castanospermum australe.

Enantioselective synthesis of (−)-meroquinene through tandem Michael reaction methodology.

Abstract An enantioselective approach to the synthesis of non natural (−)-meroquinene 1 based on sequential inter- and intramolecular Michael reaction between (L)-menthyl N-benzyl-5-amino-2E-pentenoate 3 and 1-acetyloxy-4-methoxymethyloxy-2-nitrobutane 10b , acting as surrogate of 2-nitro-1,3-butadiene 4 , is described. The heterocyclization process led to the formation of the piperidine ring system 12 , obtained as an unseparable 80:20 mixture of diastereomers at the newly created chiral centres at C-3 and C-4, which became easily separable by column chromatography after transformation of the nitrogen protective benzyl group into the corresponding carbamates 14 and 15 . Both compounds, after elaboration of the chain geminal to the nitro group into a vinyl appendage. underwent regio- and stereo-selective removal of the nitro group by palladium-catalyzed displacement with hydride generated by formate to give the precursor 19 , easily converted by treatment with hydrochloric acid to 1 , isolated as hydrochloride.