Celia Andrés

Synthesis of the novel chiral 1,3-amino alcohol 8-N,N-bis(ferrocenylmethyl)amino-menthol and its use as catalyst in the enantioselective addition of diethylzinc to aldehydes

Abstract Optically active 8-N,N-bis(ferrocenylmethyl)aminomenthol 5, obtained by condensation of (−)-aminomenthol with ferrocenecarboxaldehyde followed by N-alkylation with (ferrocenylmethyl)trimethylammonium iodide and further reduction, was found to catalyze (5 mol%) the enantioselective ethylation of aromatic, aliphatic and organometallic aldehydes to secondary alcohols with high enantioselectivities (up to 95%) at room temperature.

Stereoselective ring opening of chiral oxazolidines by reformatsky reagents: an enantioselective entry to β-amino esters.

Abstract Chiral oxazolidines obtained by condensation of aldehydes with (-).(R)- or (+).(S)-N-benzylphenylglycinol react with the Reformatsky reagent derived from ethyl bromoacetate, in mild reaction conditions (Et2O or CH2Cl2, 0°C, 15-60 min), leading to ethyl β-amino carboxylates in moderate to good diastereomeric excess (60-92%). These ring opening products are transformed into primary β-aminoesters, in one step, by debenzylation with H2/Pd on carbon without loss of their stereochemical integrity. In this way, ethyl β-amino carboxylates can be obtained in both enantiomeric forms, with chemical yields ranging 55-76% and moderate to good e.e. (60-92%).

A new chiral glycine synthon. Synthesis, x-ray structure of (−).(2S,4R)-2-ethoxycarbonyl-4-phenyl-1,3-oxazolidine and diastereoselective nucleophilic ring opening to (R)-ethyl α-amino carboxylates.

Abstract Condensation of (R)-N-benzyl-2-phenylglycinol 1 with the methyl hemiacetal of ethyl glyoxylate leads to (2S,4R)-2-ethoxycarbonyl-4-phenyl-1,3-oxazolidine 2 as the major product, obtained as a pure enantiomer after column chromatography. Compound 2 is stereoselectively cleaved by dialkylzinc reagents, prepared from alkylmagnesium iodides and ZnCl 2 , with moderate to good d.e.ś (72–94 %). These compounds, after separation by column chromatography and debenzylation by hydrogenolysis in the presence of 10% Pd on carbon, lead to enantiomerically pure ethyl α-amino carboxylates with good chemical yields.

Regio- and stereoselective 6-exo-trig radical cyclisations onto chiral perhydro-1,3-benzoxazines: synthesis of enantiopure 3-alkylpiperidines

Abstract Enantiopure 3-alkyl substituted piperidines are prepared by diastereoselective 6- exo - trig cyclisation of perhydro-1,3-benzoxazines derived from (−)-(8)-amino menthol. The diastereoselective cyclisation is promoted by tributyltin hydride, and the competitive 1,5-hydrogen migration depends on the position of the acceptor double bond and the radical site.

Diastereoselective intramolecular Diels-Alder reaction of the furan diene. A facile access to enantiopure epoxy tetrahydroisoindolines

Abstract 2-(2′-Furfuryl)-N-acryloyl tetrahydro-1,3-benzoxazine 2a participates in diastereoselective intramolecular Diels-Alder reaction in very mild conditions leading to two diastereoisomeric exo -adducts with good diastereoselectivity. Chromatographic separation of both adduts, and further elimination of the menthol appendage allows to prepare enantiopure iso -indoline derivatives in excellent chemical yields.

Highly Homogeneous Stereocontrolled Construction of Quaternary Hydroxyesters by Addition of Dimethylzinc to α‐Ketoesters Promoted by Chiral Perhydrobenzoxazines and B(OEt)3

A highly efficient enantioselective addition of Me(2)Zn to α-ketoesters, assisted by a chiral perhydro-1,3-benzoxazine ligand, is described. This novel catalytic system offers homogeneous elevated enantioselectivities in the preparation of α-hydroxyesters that bear a quaternary stereocenter, with a minor dependence on electronic and steric effects when aromatic, heteroaromatic, or aliphatic α-ketoesters are employed. The catalyst can be recovered and reused without loss of activity.

Cyanogen Bromide as a Useful Brominating Agent, Synthesis of α-Bromo-β-Aminoenones

Abstract Cyanogen bromide reacts with β-aminoenones, in very mild conditions, leading to α-bromo-β-aminoenones with excellent yields.

Diastereoselective 5-exo-trig radical cyclisation on N-Acryloyl-tetrahydro-1,3-oxazines. A novel approach to enantiopure 3-substituted pyrrolidines

Abstract N-Acryloyl-2-(phenylselenomethyl)-tetrahydro-1,3-oxazine 1 generates a carbon-centred radical in the presence of tri-n-butyltin hydride and A1BN. This radical underwent diastereoselective 5-exo-trig cyclisation leading to a mixture of five-membered lactams 2a and 2b (d.e. 68%). Chromatographic separation of the diastereomers and elimination of the chiral auxiliary provided enantiopure (R)-3-methylpyrrolidine in good chemical yield.

Synthesis of enantiopure mono- and disubstituted tetrahydroisoquinolines by 6-exo radical cyclizations

Abstract 2-( o -Bromophenyl)-3-allyl- and 2-allyl-3-( o -bromobenzyl)-substituted perhydrobenzoxazines, derived from (−)-8-amino menthol, readily cyclized stereoselectively by reaction with tributyltin hydride in the presence of AIBN. The cyclization compounds were transformed into enantiopure 4-alkyl tetrahydroisoquinolines by reductive ring opening of the N,O-acetal moiety with lithium aluminum hydride. Enantiopure 1,4- and 3,4-dialkyl-substituted tetrahydroisoquinolines were also prepared by reaction of the cyclized compounds with methylmagnesium iodide and subsequent elimination of the menthol appendage.

The Reaction of β-Aminoenones with Cyanamide. A High Efficient Synthesis of 2-Aminopyrimidines

Abstract β-aminoenones react with cyanamide, molar ratio 1:2, to yield 2-aminopyrimidines in nearly quantitative yields.