Maria L. Quiroga

SYNTHESIS OF POLYSUBSTITUTED 3-THIOFURANS BY REGIOSPECIFIC MONO-IPSO-SUBSTITUTION AND ORTHO-METALLATION FROM 3,4-DIBROMOFURAN

The synthetic potential of 3,4-dibromofuran has been assessed by its conversion into 3,4-disubstituted furans via mono-S-ipso-substitution. The ability of 3-methylthio and 3-phenylthio substituents for directing the metallation at position α-relative to the substituent has allowed the regiospecific alkylation. It provides a straightforward approach to several 3-monothiosubstituted furans which are receiving increasing interest as odour and flavour chemicals.

Diastereoselective synthesis of 4-substituted 5-(p-tolylsulfinyl)-5,6-dehydropiperidin-2-ones. A new approach to methyl L-(2S, 4S)-4-methyl-6-oxopipecolate

Abstract The sulfoxide-mediated diastereoselective Michael reaction of homochiral α-sulfinylketimines 1a – d and β-substituted ene esters 2a – d (Huas reaction) was explored. Straightforward cyclization of the open-chain adducts take place under the reaction conditions to provide the 4-substituted 5-( p -tolylsulfinyl)-5,6-dehydropiperidin-2-ones 3 and 7 – 12 , whose stereochemistry is formed in the prior step. Furthermore, the role of the metal ion of the aza-enolate reagents and the steric demands of the O -alkyl ester group have been examined. It seems that the anti -diastereoselectivity depends on metal chelation by the oxygen of the ester as well as the oxygen of the sulfinyl group and the nitrogen in the aza-enolate (( Z )-configuration). In addition, the synthesis of methyl l -(2 S ,4 S )-4-methyl-6-oxopipecolate has been achieved from the suitably functionalized 2-sulfinylketimine 1a (five steps; overall yield: 53–65%).

Stereoselective cyanosilylation of α-sulfinylketimines or its covalently stabilized enamine tautomers. Synthesis of enantiomerically pure α-sulfinylmethyl-α-amino nitriles

Abstract α-Sulfinylketimines and β-sulfinylenamines undergo reaction with delivery cyanide reagents such as TMSCN or TBDMSCN in the presence of either stoichiometric excesses of ZnCl 2 or ZnBr 2 , or catalytic amount of Yb(TfO) 3 . The use of ZnCl 2 in alcohol solvents provides the best diastereoselectivity. It is mediated by a chelated transition state, the p -tolyl group driving the anti attack of the reagent. By using Yb(TfO) 3 poor diastereoselectivities but good yields are obtained. It seems that an iminium derivative originated by metal coordination with either the nitrogen or oxygen atom in the substrate is responsible for the observed results. Interestingly, β-sulfinylenamines provide analogous α-amino nitriles in the same reaction conditions. It allowed the cyanosilylation of the covalently stabilized enamines arising from unstable β-sulfinyl aldehydes.

A novel synthesis of thiazoles from dimethyl N-(ethoxycarbonylmethyl)imino dithiocarbonate, carbon disulfide and alkyl halides

Abstract We report a new synthesis of thiazoles from a cyclocondensation reaction between dimethyl N-(ethoxycarbonylmethyl)iminodithiocarbonate (EMIC), carbon disulfide and alkylation of intermediate thiazole-2-thiolate with alkyl halides.

A novel synthesis of 2,3-dihydrooxazoles from dimethyl N-ethoxycarbonylmethyliminodithiocarbonate and aromatic aldehydes

Abstract We report the synthesis of 5-aryl-2-ethoxycarbonyl-4-methylthio-2,3-dihydrooxazoles from a cyclocondensation reaction betweeen dimethyl N-ethoxycarbonylmethyliminodithiocarbonate and aromatic aldehydes.

Assignment of relative configurations to diastereomeric carbinols with lanthanide shift reagent[eu(fod)3] : Application to 1-mesltyl-2-methyl-3-phenyl-1-propanol

Abstract Assignment of relative configurations to the diastereomeric racemates (1R2R, 1S2S) and (1R2S, 1S2R) of 1-mesityl-2-methyl-3-phenyl-1-propanol was carried out, by studing the chemical shifts induced by Eu(fod)3 an the signal of the Me group in position 2, taking into account a prior estimate of the populations of significant forms in both diastereomers.

Reduction of Chiral Acyclic Ketones with Hydride-transfer Agents. Semiempirical Analysis of the Observed Stereoselectivity

(±)-2,2,6,6-Tetramethyl-5-phenylheptan-3-one (1), (±)-4,4-dimethyl-1,3-diphenylpentan-1-one (2), (±)-2-methyl-1,3-diphenylpropan-1-one (3), and (±)-2,3,3-trimethyl-1-phenylbutan-1-one (4) have been reduced with lithium tetrahydridoaluminate (LAH), sodium tetrahydridoaluminate (NAH), lithium tri-t-butoxyhydridoaluminate (LTBHA), lithium tetrahydridoborate (LBH), lithium tri-s-butylhydridoborate (LS = lithium selectride) and potassium tri-s-butylhydridoborate (KS = potassium selectride) using different solvents and reaction conditions. For ketones (1) and (2) some correlations with the observed stereoselectivity have been found. The applicability of a semiempirical scale for the effective size of reagent to the stereochemical analysis of the observed asymmetric induction has been tested.

On the synthesis of α-di-(methylmercapto)-methylene derivatives of symmetrical ketones

The generation of synthetic intermediates α-di-(methylmercapto)-methylene ketones 1 has been optimized. Selection of the best base/solvent system for quantitative formation of 1 is justified.

A new synthetic approximation to thiazoles with a versatile persubstitution and/or perfunctionalization

A new synthetic approach to 2-alkyl-, 2-aryl-, and 2-N-alkylaminothiazoles has been carried out. This strategy is based on the high versatility of synthons derived from 2-methylthiothiazoles

Stereoselectivity in the condensation reactions of 1-phenylethyl alkyl and phenyl ketones with organometallic reagents

Stereochemical results of the condensation reactions of a series of ketones, PhCHMeCOR (R = Me, Et, Pri, But, Ph), with various organomagnesium and organolithium derivatives in ethers as solvents are reported. Results are accounted for on the basis of competition between two transition states which may adopt either Karabatsos- or Felkin-type conformations according to the nature of R, the reagent nucleophilicity, and the polarity of solvent. Polar and steric analysis of this reaction allows highly stereoselective syntheses of diastereoisomeric α-phenylalkanols to be devised.