Possibilities of Exploiting Kinetic Control in the Continuous Fractional Crystallization of Diastereomeric Mixtures

For rapid and kinetic control-influenced resolutions, it is advisable to choose a resolving agent with the highest possible eutectic composition (eeEuResAg). It may also be advantageous to add the crystalline resolving agent directly to the solution of the racemic compound. In addition, the use of a quasi-racemic resolving agent or amphoteric resolving agent can provide kinetic resolution. In some cases, the continuous fractional crystallization of diastereomeric salts requires the salt of the resolving agent (Ca2+, Na+, etc.) or other achiral additives (thiourea) that cause rapid crystallization and provide high diastereomeric purity. A further advantage may be the sequential use of the same resolving agent that is capable of forming crystalline diastereomers with both enantiomers when using kinetic control (tandem resolution).

Kinetic Separation of cis-and trans-Limonene Epoxide: Reaction of Diastereomeric Mixture of Limonene Oxides with Secondary Amine and Carbamate

A simple kinetic separation of (1:1) diastereomeric mixture of limonene oxides was used to purify cis-and trans-diastereomers of (R)-(+)-limonene oxide. The epoxide ring of trans-isomer was selectively opened by (R)-N-methyl-(α-methyl-benzyl)amine. This secondary nucleophilic amine left cis-limonene oxide largely unreacted and was obtained up to 90% yield. In a diverse way, (R)-N-(α-methylbenzyl) ethyl carbamate, selectively catalyze hydrolysis of cis-limonene oxide to 1,2-limonene diol leaving trans-limonene oxide largely unreacted. The unreacted trans-limonene oxide was recovered in up to 75% yield. HPLC and NMR analyses were used to demonstrate that the isolation of cis-and trans-diastereomers of (R)-(+)-limonene oxide has shown that > 98% were pure. As a result, depending on the realization of the secondary amine or carbamate in the presence of water, either cis-or trans-limonene oxide may be obtained in high diastereomeric purity.

Ancistrotectoquinones A and B, the First Quinoid Naphthylisoquinoline Alkaloids, from the Chinese Liana Ancistrocladus tectorius

From the leaves and stems of Ancistrocladus tectorius (Ancistrocladaceae) from the Chinese island Hainan, two novel-type 7,3′-coupled naphthylisoquinolines, named ancistrotectoquinones A (4) and B (5), were isolated. They are the first alkaloids with a 1,4-naphthoquinone portion coupled to an isoquinoline moiety. Due to the lowered degree of steric hindrance next to the biaryl axis and for electronic reasons, 4 and 5 occur as pairs of configurationally semi-stable, and, thus slowly interconverting atropo-diastereomers. The Gibbs free energies of activation between the two atropisomers of ancistrotectoquinone A (4a/b) were determined by measuring the time-dependent decrease of diastereomeric purity of freshly separated samples enriched with the M- or P-atropisomer and, computationally, by DFT calculations. The absolute configurations at the biaryl axes of the atropo-diastereomers of 4a/b and 5a/b were assigned by online LC-CD analysis. The stereostructure of 4a/b was further confirmed by its semi-synthesis from the likewise 7,3′-coupled ‘normal' naphthylisoquinoline alkaloid ancistrotectorine (6), by biomimetic oxidation with Fremy's salt.

Selective synthesis of E-isomers of aldoximes via a domino aza-Michael/retro-Michael reaction

A highly stereoselective synthesis of E-isomer of aldoximes was developed through a base-catalysed domino aza-Michael/retro-Michael reaction of hydroxylamine and 2-(R-benzylidene)malononitrile. This reaction generates (E)-aldoxime diastereomer in high yields (eight examples, isolated yields of 82-93 %), excellent diastereomeric purity (diastereomeric ratio higher than 95: 5 by 1H NMR), and proceeds under mild reaction conditions (aqueous NaOH, pH 12, room temperature, 4 h).

Stereoselective Synthesis of 2-Substituted Pyrrolidines

Using O-pivaloyl protected D-galactopyranosylamine and D-arabinopyranosylamine, (S) or (R) configured α-substituted homoallylamines are synthesized with high diastereoselectivity by reaction of the corresponding aldimines with allyltributylstannane. Electrophile-induced endo-trig-cyclization of these N-glycosylhomoallylamines gave the 2-substituted pyrrolidines of high diastereomeric purity.