Mario Ordóñez

Diastereoselective reduction of β-ketophosphonates derived from amino acids. A new entry to enantiopure β-hydroxy-γ-aminophosphonate derivatives

Abstract The reduction of γ-N,N-dibenzylamino-β-ketophosphonates 4 derived from readily available (S)-tribenzylated amino acids was achieved with catecholborane at –20°C affording γ-amino-β-hydroxyphosphonates 5 in high diastereoselectivity and good chemical yield. These reactions provide a new entry to enantiomerically pure γ-amino-β-hydroxyphosphonates.

Preparation of (R)- and (S)-γ-amino-β-hydroxypropylphosphonic acid from glycine

Abstract An efficient synthesis of both enantiomers of γ-amino-β-hydroxypropylphosphonic acid, an analogue of GABOB, has been achieved for the first time starting from glycine, through the resolution of dimethyl (±)-3-( N , N -dibenzylamino)-2-hydroxypropylphosphonate 7 with ( S )- O -methylmandelic acid.

Enantioselective Diels-Alder reactions catalyzed by chiral magnesium lewis acids prepared from hydroxysulfoxides

Abstract Enantioselective Diels-Alder reactions were conducted successfully using chiral magnesium complexes prepared from magnesium iodide and chiral hydroxysulfoxides derived from ( R )- and ( S )-methyl 1-naphthyl sulfoxide. Convenient methods for the preparation of these chiral sulfoxides have also been developed. Hydroxysulfoxide 6 (and its enantiomer 10 ) showed the highest enantioselectivity.

A convenient synthesis of (E)-γ-hydroxy- and (E)-γ-keto-α,β-unsaturated sulfoxides

Abstract ( E )- γ -Hydroxy and ( E )- γ -keto- α , β -unsaturated sulfoxides have been easily prepared in good chemical yield from simple aldehydes 2 and chiral bis-sulfoxide 4 using a SPAC-type reaction. The onepot procedure is based on a Knoevenagel condensation, subsequent prototropic shift and [2,3] sigmatropic sulfoxide-sulfenate rearrangement.

Conformational analysis of 2-halotetrahydrothiopyran S-oxides. Diminution of the anomeric effect in S(O)-C-X compared to S-C-X segments.

Abstract Direct integration of appropriate 1 H and 13 C NMR signals in the low-temperature (below coalescence) spectra of the title heterocycles permitted the estimation of the equilibrium constant for their conformation equilibria. The small but definite predominance of the isomers with axial CBr and CCl bonds in cis -2-halotetrahydrothiopyran S -oxide is contrary to expectation in terms of simple additivity rules, and supports the existence of a n s (o) → σ* C-X stereoelectronic interaction, which seems to be, nevertheless, less important than the corresponding n s → σ* C-X interaction in 2- halotetrahydrothiopyrans. The conformational presence of trans -2-halotetrahydrothiopyran S -oxides to adopt the diaxial conformation (δ G ° = ca. 0.3 kcal/mol) probably reflects the influence of repulsive electrostatic (dipole-dipole) interactions in the diequatorial conformer.

Palladium-Catalyzed Allylic Nucleophilic Substitution Reactions of (E)-γ-Acetoxy-α,β-unsaturated p-Tolylsulfoxides.

Abstract Regio- and diastereoselective nucleophilic allylic substitutions of optically pure (E)-γ-acetoxy-α,β-unsaturated p-tolylsulfoxides 2 and 3 with sodium dimethyl malonate have been carried out. The reactivity of these substrates is controlled by both the chiral sulfinyl group and the size of the alkyl group attached at the γ-terminus of the allylic system. This process constitutes an example of palladium-mediated resolution of a 1:1 mixture of acetates 2 and 3.

Efficient preparation of enantiomerically pure (E)-γ-hydroxy-α,β-unsaturated p-tolylsulfoxides using lipase-mediated acylations

Abstract ( E )-γ-Hydroxy-α,β-unsaturated p -tolylsulfoxides 1 have been efficiently resolved via irreversible enzymatic acylation with lipase PS ( Pseudonomas cepacia ) and vinyl acetate.

Study of the fragmentation pathway of α‐aminophosphonates by chemical ionization and fast atom bombardment mass spectrometry

The diastereoisomers of α-aminophosphonates are key intermediates in the synthesis of enantiomerically pure α-aminophosphonic acids, which are analogs of α-amino acids. Although several methods have been reported for the diastereoselective synthesis of α-aminophosphonates, their mass spectrometry (MS) fragmentation patterns have not yet been fully investigated. The work described here involved a detailed study of the fragmentation of enriched α-aminophosphonate diastereoisomers by chemical ionization (CI-MS) and fast atom bombardment (FAB)-MS. The complete characterization of the different conventional MS fragmentation pathways is represented and this intriguing exercise required the use of tandem mass spectrometry (MS/MS) experiments and high-resolution accurate mass measurements. All α-aminophosphonates gave prominent pseudomolecular ions, protonated molecules [MH](+) , and their fragmentations mainly showed a loss of dimethyl phosphite to give the corresponding iminium ions as base peaks for α-aminophosphonates bearing methylbenzyl and 2,2-dimethylbutyl fragments. The loss of the chiral fragment from the iminium ions bearing the (S)-1-(1-naphthyl)ethyl group gave rise to a base peak due to aryl cations. The nature of all fragment ions were confirmed by high-resolution mass spectrometry (HRMS).

Asymmetric alkylation of dimethoxyphosphoryl-N-[1-(S)-α-methylbenzyl]acetamide enolates. Synthesis of both stereoisomers from the same source of chirality by changing the equivalents of LDA

A new methodology has been developed for the synthesis of both stereoisomers from a single chiral source.

Novel naphthalimide–aminobenzamide dyads asOFF/ONfluorescent supramolecular receptors in metal ion binding

Abstract A series of novel naphthalimide–aminobenzamide (NAPIM-2ABZ) dyads 3 connected by different length polymethylene chains were synthesized and studied as fluorescent supramolecular receptors in metal ion binding. The photophysical properties were evaluated and compared with separated chromophores. The electronic absorption spectra of dyads 3 showed no interaction between chromophores in the ground state. The fluorescence quantum yields were lower in dyads 3 in comparison with N-propyl-2-aminobenzamide (8). The fluorescence quenching is attributed to a PET mechanism between fluorophores (from 2ABZ to NAPIM), which is dependent on the polymethylene chain length. In metal binding study was found a response towards transition metal ions such as Hg(II), Cu(II), Zn(II) and Ni(II). Dyad 3b presented selectivity towards Cu(II). The UV-vis, IR and 1H-NMR studies demonstrated the interaction with 2ABZ moiety in the ground state, and interestingly dyads with shorter polymethylene chains 3a (n = 0), 3b (n = 1) and 3c (n = 2) exhibited an OFF/ON fluorescence behaviour due to the PET inhibition and the quenching of 2ABZ fluorescence. Dyads 3d (n = 4) and 3e (n = 6) presented opposite response ON/OFF in the complex with metal ions evidencing the absence of PET in these dyads.