Mireia Pastó

Fine-Tuning of Modular Amino Alcohol Ligands for the Enantioselective Transfer Hydrogenation of Ketones

A family of stereodefined, modular amino alcohols (3-alkoxy-1-amino-1-phenyl-2-propanols), in which the steric bulk of the alkoxy and amino substituents varies smoothly, has been synthesized from enantiomerically pure phenylglycidol, prepared by Sharpless epoxidation. These amino alcohols have been evaluated as ligands in the catalyzed [(amino alcohol)(arene)RuII] transfer hydrogenation of alkyl aryl ketones, with 2-propanol as the hydrogen source. Both the nitrogen substituent and the alkoxy group have been optimized for maximal enantioselectivity and catalytic activity in the process under consideration. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

An enantioselective, stereodivergent approach to anti- and syn-α-hydroxy-β-amino acids from anti-3-amino-1,2-diols. Synthesis of the ready for coupling taxotere® side chain.

Abstract Both anti- and syn-α-hydroxy-β-amino acids are efficiently synthesized in protected form and high enantiomeric purity from readily available anti-N-Boc-1-tert-butyldimethylsilyl-3-amino-1,2-diols. The preparation of the anti series is straightforward, and takes place by protection of the secondary hydroxyl group (1-ethoxyethyl) followed by desilylation/oxidation of the primary hydroxyl group. For the preparation of the syn isomers, the secondary alcohol is inverted at the beginning of the sequence by Mitsunobu methodology (p-nitrobenzoate). Starting from homochiral (2S,3S)-N-Boc-1-tert-butyldimethylsilyl-3-amino-3-phenylpropane-1,2-diol, the ready for coupling Taxotere® side chain has been prepared in enantiomerically pure form.

A CONVENIENT, STEREODIVERGENT APPROACH TO THE ENANTIOSELECTIVE SYNTHESIS OF N-BOC-AMINOALKYL EPOXIDES

Abstract An efficient, stereodivergent and enantioselective synthesis of N-Boc-aminoalkyl epoxides has been developed. Starting from enantiomerically enriched anti N-diphenylmethyl-3-amino-1,2-diols, and after a change in the nitrogen protecting group, an intramolecular Mitsunobu reaction leads to the erythro aminoalkyl epoxides; a three step sequence consisting of protection of the primary alcohol, activation of the secondary alcohol and simultaneous deprotection/cyclization affords in good yields the corresponding threo isomers.

Highly enantioselective dynamic kinetic resolution and desymmetrization processes by cyclocondensation of chiral aminoalcohols with racemic or prochiral δ-oxoacid derivatives

Cyclocondensation reactions of aminoalcohols and with racemic or prochiral delta-oxoacid derivatives provide polysubstituted lactams with high enantioselectivity in a process that involves dynamic kinetic resolution and/or desymmetrization of enantiotopic or diastereotopic ester groups.

Enantioselective synthesis of fully protected anti 3-amino-2-hydroxy butyrates

Abstract An efficient enantioselective synthesis of fully protected anti 3-amino-2-hydroxybutyrates has been developed. Starting from enantiomerically enriched anti N-diphenylmethyl-3-amino-1,2-butanediol, after a change in the nitrogen protecting group, the primary alcohol was protected by regioselective reduction of the corresponding p-methoxybenzylidene acetal. Formation of the oxazolidine and deprotection of the primary alcohol followed by oxidation afforded protected α-hydroxy-β-amino acids in good yield. Since the source of asymmetry is a catalytic Sharpless epoxidation, both enantiomeric series are available and the methodology developed here is expected to be of broad applicability.

Chiral derivatives of semisquaric acid as new modular ligands for asymmetric catalysis

A family of enantiomerically pure ligands based on the cyclobutenedione structure, and containing either an enantiomerically pure amino alcohol or a diamine as the chiral element, has been synthesized. As first examples of their application, these versatile and modularly constructed ligands have been tested in the transfer hydrogenation of acetophenone and in the reduction using borane of this same substrate.

Enantioselective synthesis of N-Boc-2,2-dimethyloxazolidine-5-carbaldehydes, versatile precursors of dipeptide isosteres

Abstract Highly enantioenriched cis and trans N-Boc-2,2-dimethyl-oxazolidine-5-carbaldehydes have been efficiently prepared from N-Boc-3-amino-1,2-alkanediols, readily available in enantiopure or enantioenriched form by Sharpless epoxidation methodology. These compounds have been converted into N-Boc-(S)-γ-[(S)-1-aminoalkyl]-γ-lactones which are key intermediates of hydroxyethylene dipeptide isosteres.