Alfonso González

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.

The Reaction of b-Aminoenones with a-Amino Derivatives. Synthesis of 2-Functionalized Pyrroles

β-Aminoenones react with ethyl glycinate, α-aminoacetonitrile and α-aminoacetamide hydrochlorides leading to 2-functionalized pyrroles. Although the transamination is a high-yield process, the transformation of the intermediate, in both basic or thermally induced conditions, affords the corresponding pyrroles in poor to moderate yields

Regioselective Synthesis of 2-Functionalized Thiophenes by Condensation of α-Mercapto Compounds with β-Aminoenone Derivatives

Abstract 2-Acylthiophenes and ethyl 2-thiophene-carboxylates are prepared regioselectively by reaction of 3-ctil oroenones and 2-acylenammoni urn chlorides with α-mercapto derivatives in good to moderate yields.

Regioselective Synthesis of 2- and 3-Acylpyrroles by Reaction of b-Aminoenones with a-Aminoketone Hydrochloride

A high regioselective synthesis, with good to excellent yields, of 2- and 3-acylpyrroles from β-aminoenones and α-aminoketones is described. The formation of 2-acylpyrroles or their 3-acylisomers depends on the pattern substitution on the reactants

Some Observations on the Reactivity of b-Aminoenones towards Phenacylamine Hydrochloride

β-Aminoenones react with phenacylamine hydrochloride to give mixture of 2- and 3-acylpyrroles. The reaction is a two steps process: formation of an isolable β-phenacylaminoenone intermediate, and cyclization of this to the final 2- and/or 3-acylpyrroles, depending on the substituents on the starting compounds

An Efficient Synthesis of 3-tert-Aminopropanol Derivatives by Regioselective Ring Opening of Tetrahydro-1,3-oxazines with Grignard Reagents

Abstract N-Benzyl tetrahydro-1,3-oxazines react with methylmagnesium iodide, benzylmagnesium bromide, allylmagnesium chloride and phenylmagnesium bromide affording 3-tert-aminopropanol derivatives with excellent yields. By contrast, the same substrates do no react with sodium phenylacetilide or butyllithium, and the corresponding tetrahydro-1,3-oxazinium methiodides are also inert toward Grignard reagents.

Differential reactivity of β-amino enones and 3-dimethylaminoacrylaldehyde towards α-amino derivatives

Unsubstituted β-amino enones react with α-amino derivatives by a well established route which implies a fast transamination process — 1,4-addition followed by elimination — and cyclodehydration of the intermediate to 3-functionalized pyrroles. In contrast, 3-dimethylaminoacrylaldehyde undergoes 1,2-addition followed by cyclization to give the final 2-substituted pyrroles. Isolation of the intermediates supports the proposed mechanism for each reaction.

Alkylation of 3,5-Dimethylisothiazole. A Regioselective Synthesis of S-Alkyl-3-methylisothiazoles

Abstract 3,5-Dimethylisothiazole reacts sequentially with lithiumdiisopropylamide (molar ratio 1:1) and alkyl halides (in excess) affording 5-alkyl-3-methylisothiazoles in excellent yields. When a two-fold excess of base is used, a mixture of 5-monoalkylated and 3,5-dialkylated products is obtained. Sodium amide was also tried as deprotonating agent, but the yield in final products was lower.

SOME OBSERVATIONS ON THE REGIOSELECTIVE RING OPENING OF TETRAHYDRO-1,3-OXAZINIUM METHIODIDES BY SODIUM BOROHYDRIDE IN ALCOHOLIC AND ETHEREAL SOLVENTS

2-Substituted N-benzyl-N-methyltetrahydro-1,3-oxazinium iodides react with sodium borohydride in anhydrous THF leading to a mixture of 3-alkoxypropylamines and their borane complexes. On the contrary, when anhydrous methanol or ethanol is used as solvent, the corresponding transacetalization product is obtained as single compound