José M. Villalgordo

Synthesis of a novel heterospirocyclic 3-(N-methyl-N-phenylamino)-2H-azirine and its use as an amino acid equivalent in the preparation of a model tripeptide

Abstract The synthesis of a novel heterospirocyclic 3-amino-2H-azirine based on the reaction between amide enolates and diphenylphosphorochloridate is described. This compound has been shown to be a useful amino acid equivalent and the synthesis of a model tripeptide was achieved in good overall yields.

Reaction between hydrazines and chiral α-acetylenic ketones: synthesis of novel enantiomerically pure pyrazolyl-β-amino alcohols

Abstract A simple and efficient methodology toward the stereoselective synthesis of novel, enantiomerically pure, pyrazolyl-β-amino alcohols is presented. Thus, when hydrazines 4a,b were allowed to react at 0°C with chiral α-acetylenic ketones of type 3, pyrazolyl oxazolidine derivatives 5a–d were formed with total regioselectivity in 92–97% yield. Subsequent oxazolidine ring opening by means of TFA, and re-protection of the amino group as the N-Boc derivatives, afforded enantiopure amino alcohols 7a–d.

Reaction of α-iminomethylene amino esters with mono- and bidentate nucleophiles: a straightforward route to 2-amino-1H-5-imidazolones

Abstract The reaction between α-iminomethylene amino esters with different mono- and bidentate nucleophiles has been studied. It has been shown that the reactions with primary and secondary amines as monodentate nucleophiles afford 2-aminoimidazolones efficiently under very mild conditions. Judicious selection of the primary amines employed can modulate the regioselectivity. Analogous reactions employing bidentate nucleophiles (e.g. amidines) also afford imidazolyl derivatives. The formation of the latter is preferred over the formation of seven-membered heterocycles of the triazepinone type. The optimized methodology in solution described herein should be readily adaptable to use in the solid phase for the parallel synthesis of collections of 2-aminoimidazolone derivatives with a high degree of molecular diversity.

A highly efficient and straightforward stereoselective synthesis of novel chiral α-acetylenic ketones

Abstract A very efficient and straightforward synthesis of novel chiral α-acetylenic ketones of type 3 has been developed. Starting from commercially available l -(−)-serine 4, and through the Garners aldehyde 5, ethynyloxazolidine 2 was formed in good overall yield. Condensation of the corresponding lithium acetylide 7 with different aliphatic and aromatic aldehydes 5 and 8a–h at low temperatures yielded the respective propargylic alcohols 9a–i. Subsequent mild oxidation of 9a–i with 10-I-4-iodinane oxide (IBX) 12 afforded chiral α-acetylenic ketones 3a–i almost quantitatively.

exo,exo-2-Amino-3-borneol-derived oxazolidinone as a new chiral auxiliary for use in asymmetric transformations

N-Acylimides derived from exo,exo-2-amino-3-borneol when subjected to alkylation, Diels–Alder reaction, and conjugate additions afford the corresponding products with a high level of asymmetric induction, particularly in those cases of inherent poor diastereofacial selectivity.

Synthesis of novel optically pure quinolyl-β-amino alcohol derivatives from 2-amino thiophenol and chiral α-acetylenic ketones and their IBX-mediated oxidative cleavage to N-Boc quinolyl carboxamides ☆

Abstract A methodology directed toward the stereoselective synthesis of novel quinolyl glycines is presented. This strategy is based on the cyclocondensation reaction between 2-amino thiophenol 4 and chiral acetylenic ketones of the type 3 containing a latent α-amino acid functionality. The initially formed benzo[b][1,4]thiazepine derivatives 5, readily undergo sulphur extrusion in refluxing toluene to yield the corresponding 2,4-disubstituted quinolines 6. Subsequent oxazolidine ring opening followed by in situ re-protection of the amino group afforded the corresponding quinolyl-β-amino alcohols 8a–8f in enantiomerically pure form and good overall yields. The derivatives 8 are in principle suitable precursors for the synthesis of novel optically pure quinolyl glycines through oxidation of the alcohol side chain. However, these amino alcohol derivatives 8, did not afford the expected quinolyl glycines 10 using numerous oxidising agents and reaction conditions. Instead, by reacting 8 with the mild oxidising reagent IBX 11, an oxidative CC cleavage leading to the N-Boc quinolyl carboxamides 12 took place.