Maria D. Rozwadowska

Density Functional Theory Calculations of the Optical Rotation and Electronic Circular Dichroism: The Absolute Configuration of the Highly Flexible trans-Isocytoxazone Revised

Ab initio calculations of the optical rotation (OR) and electronic circular dichroism (ECD) for a series of trans-diastereomers of the natural cytokine modulator cytoxazone 1-4 have been performed by density functional theory (DFT). The calculation of OR and ECD curves provides, after critical assessment, a reliable method for the assignment of absolute configuration of these conformationally flexible molecules. The effects of the level of theory used for calculations, changes of conformer equilibrium, and the solvent influence on the geometry and values of calculated OR data are discussed, leading to the conclusion that the most frequently used B3LYP/6-31G(d) method is not adequate for prediction of the absolute configuration of this type of highly flexible molecules. The absolute configurations of levorotatory trans-isocytoxazone 2 and analogues 1, 3, and 4 have been established as (-)-(4S,5S)-trans-1-4; i.e., it is in opposition to the previously published configuration (-)-(4R,5R)-trans-2.

Cyanohydrins as substrates in benzoin condensation. : Regiocontrolled mixed benzoin condensation

Abstract O-Benzoylated cyanohydrins of aromatic aldehydes have been used as one of the substrates in the benzoin condensation. They were treated with aromatio aldehydes under phase-transfer conditions to result in benzoin benzoates. By this method aldehydes which fail to undergo condensation using traditional conditions could be converted into benzoins. By the Umpolung of reactivity of the pertinent aldehyde it was possible to prepare both isomeric unsymmetrical benzoins, including the thermodynamically less stable ones.

Enantioselective modification of the Pomeranz–Fritsch–Bobbitt synthesis of tetrahydroisoquinoline alkaloids synthesis of (−)-salsolidine and (−)-carnegine

Abstract (−)-Salsolidine 7 and (−)-carnegine 8 were prepared in 46 and 36% e.e. , respectively, by enantioselective addition of methyllithium to the Pomeranz–Fritsch imine 13 in the presence of ligands 9 – 12 , followed by acid-catalyzed cyclization and hydrogenolysis.

Stereoselective synthesis of 3-mono- and 1,3-disubstituted 4-phenyl-1,2,3,4-tetrahydroisoquinolines

Abstract (1 S ,2 S )-(+)-Thiomicamine was transformed in high yield and with high diastereoselectivity into (3 R ,4 R )-4-phenyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid and enantiomerically pure (3 R ,4 R ) - 3-hydroxymethyl-4-phenyl- and (1 R ,3 R ,4 R ) - 3-hydroxymethyl-1-methyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline derivatives.

An efficient synthesis of S-(+)-amphetamine

Abstract Optically active ( S )-(+)-amphetamine hydrochloride ( 5 ·HCl) was prepared from ( 1S,2S )-2-amino-1-phenyl-1,3-propanediol ( 1 ) via its 3 -iodo intermediate ( 3 ). A phthaloyl group was used for protecting the amine function.

Transformation of (+)-thiomicamine into a new ligand for the enantioselective addition of methyllithium to prochiral imines

Abstract A new ligand 2 was prepared from (+)-thiomicamine 1 and o-methoxyphenol, and its activity as an external controller of stereochemistry in enantioselective additions of methyllithium to prochiral imines 8–10 tested. The non-racemic secondary amines 11–13 were prepared in 60–90% chemical yield with the enantioselectivity ranging from 2 to 41%. 6,7-Dimethoxy-3,4-dihydroisoquinoline 8 was transformed into (+)-salsolidine 11 with an e.e. of 41%.

A concise synthesis of (R)-(+)-phenylalaninol from (1S,2S)-(+)-thiomicamine

Abstract ( R )-(+)-Phenylalaninol 6 was obtained from oxazolines 3 and 4 derived from (1 S ,2 S )-2-amino-1-aryl-1,3-propanediols 1 and 2 by the action of Raney nickel followed by hydrolysis of the intermediate benzamide 5 .

Enantioselective alkylation of reissert compounds in phase transfer catalysed reactions

Isoquinoline Reissert compounds were alkylated under phase-transfer reaction conditions using chiral quaternary ammonium salts derived from Cinchona alkaloids as catalysts. The best stereoselectivity (ee up to 65%) was achieved in the alkylation of 1-cyano-2-phenoxycarbonyl-1.2-dihydroisoquinoline (1d), catalysed by N-benzylcynchoninium bromide (3a), carried in toluene/50% NaOH biphasic system.

Synthesis and spectroscopic studies of some hydrogenated thiazolo[2,3-a]isoquinolines

Abstract Dihydro-5 H -thiazolo[2,3- a ]isoquinolinones ( 1 – 6 ) and tetrahydro-5 H -thiazolo[2,3 a ]isoquinolines ( 7 – 12 ) have been prepared from 3,4-dihydroisoquinoline derivatives under the action of α-mercapto alkanoic acids or ethylene sulfide, respectively. In the synthesis of compounds 2 and 5 isothiocarbostril ( 13 ) and N -thioacetyl-β-phenylethylamine derivatives ( 14 ), respectively, were also used as substrates and treated with bromoacetic acid derivatives. Spectral characteristics (IR, 1 H, 13 C NMR and MS) of compounds 1 – 12 are presented.

Air oxidation of Reissert compounds

Reissert compounds undergo autoxidation in basic solution giving rise to isoquinaldo- or quinaldonitriles. Under the same reaction conditions, dihydroisoquinoline Reissert compounds undergo oxidative decyanation to dihydroisocarbostirils. The intermediacy of α-peroxycyanides is proposed in this transformation.