No abstract

Proton abstraction of N-tert-butoxycarbonyl-piperidine (N-Boc-piperidine) with sBuLi and TMEDA provides a racemic organolithium that can be resolved using a chiral ligand. The enantiomeric organolithiums can interconvert so that a dynamic resolution occurs. Two mechanisms for promoting enantioselectivity in the products are possible. Slow addition of an electrophile such as trimethylsilyl chloride allows dynamic resolution under kinetic control (DKR). This process occurs with high enantioselectivity and is successful by catalysis with substoichiometric chiral ligand (catalytic dynamic kinetic resolution). Alternatively, the two enantiomers of this organolithium can be resolved under thermodynamic control with good enantioselectivity (dynamic thermodynamic resolution, DTR). The best ligands found are based on chiral diamino-alkoxides. Using DTR, a variety of electrophiles can be used to provide an asymmetric synthesis of enantiomerically enriched 2-substituted piperidines, including (after Boc deprotection) the alkaloid (+)-beta-conhydrine. The chemistry was extended, albeit with lower yields, to the corresponding 2-substituted seven-membered azepine ring derivatives.

The new compounds 1-aryl-3-{1-phenyl-3-[p (methylthio)phenyl]pyrazol-4-yl}-2-propen-1-ones 2a?l were prepared by the condensation of 1-phenyl-3-[p (methylthio)phenyl]-4-formylpyrazole 1 with different aryl ketones. Compounds 2a?l in reaction with hydrazine hydrate yielded 3-aryl-5-{1-phenyl-3-[p-(methylthio)phenyl]pyrazol-4 yl}-4,5-dihydro-(1H)-pyrazoles 3a?l and in the presence of hydrazine hydrate in glacial acetic acid gave 1-acetyl-3-aryl 5-{1-phenyl-3-[p-(methylthio)phenyl]pyrazol-4-yl}-4,5 dihydro-(1H)-pyrazoles 4a?l. These compounds were tested in vitro for their antitubercular and antimicrobial activities. The in vitro antimycobacterial activity of the newly synthesized compounds was investigated against Mycobacterium tuberculosis H37RV (ATCC 27294) in BACTEC 12B medium using the ALAMAR radiometric system. The antimicrobial in vitro activity was tested against Bacillus coccous, Bacillus subtilis Escherichia coli, Proteus vulgaris and antifungal activity against Aspergillus niger. The structures of the synthesized compounds were assigned on the basis of elemental analysis IR, 1H NMR and mass spectral data.

Dynamic thermodynamic resolution of N-Boc-2-lithiopiperidine is possible using a chiral ligand; the two enantiomers of this organolithium can be resolved with selectivities of up to 85 : 15 from a selection of 26 chiral diamino-alkoxide ligands screened.