1. Optimisation of a lithium magnesiate for use in the non-cryogenic asymmetric deprotonation of prochiral ketones
Silvia Zaragoza-Calero, Javier Francos, Charles T O'Hara Dalton Trans . 2014 Jan 21;43(3):1408-12. doi: 10.1039/c3dt52577e.
A study has been conducted to determine whether lithium magnesiates are feasible candidates for the enantioselective deprotonation of 4-alkylcyclohexanones. The commercially available chiral amine (+)-bis[(R)-1-phenylethyl]amine (2-H) was utilised to induce enantioselection. When transformed to its lithium salt and combined with (n)Bu2Mg, improved enantioselective deprotonation of 4-tert-butylcyclohexanone (with respect to the monometallic lithium amide) at 20 °C was observed. In an attempt to optimise the reaction further, different additives were added to the lithium amide. The best performing deprotonations at 0 °C were those in which (Me3SiCH2)2Mg (er pro-S 74 : 26) and (Me3SiCH2)2Mn (er pro-S 72 : 28) were added, hence the lithium magnesiate "LiMg(2)(CH2SiMe3)2" was used in the remainder of the study. The optimum solvent for the reaction was found to be THF. NMR spectroscopic studies of a D8-THF solution of "LiMg(2)(CH2SiMe3)2" appear to show that this mono-amide bis-alkyl species is in equilibrium with a bis-amide mono-alkyl compound (and a tris-alkyl lithium magnesiate). When a genuine bis-amide lithium magnesiate solution is used, the deprotonation results were essentially identical to those obtained for "LiMg(2)(CH2SiMe3)2". By adding LiCl to "LiMg(2)(CH2SiMe3)2" the er at 0 °C improved to 81 : 19. At -78 °C good yields and an er of 93 : 7 were obtained. This LiCl-containing base was used to successfully deprotonate other 4-alkylcyclohexanones.
2. Experimental and theoretical studies on the enantioselectivity of molecularly imprinted polymers prepared with a chiral functional monomer
D Mariano A Vera, Carlos A Chesta, Natalia Gsponer, Hernán A Montejano, Cristina L Ramírez, Juan J Torres J Chromatogr A . 2012 Nov 30;1266:24-33. doi: 10.1016/j.chroma.2012.09.042.
A comprehensive study on the enantioseparation of racemic bis[1-phenylethyl]amine (PEA) on a series of molecularly imprinted polymers (MIPs) prepared using the chiral functional monomer (S)-2-(2-methyl-acryloylamino)-3-phenyl propionic acid (MAPP) is reported. MIP-R, MIP-S and MIP-RS, were synthesized separately by imprinting the pure enantiomers (R-, S-PEA) and racemic PEA, respectively, MAPP, EDGMA as crosslinker and chloroform as the porogen. It was found that all MIPs prepared were able to resolve the PEA racemate. Residence times (t(r)) and enantioselectivity factors (α) were estimated from typical elution chromatography experiments. Frontal chromatography experiments were conducted to acquire the adsorption isotherms for both enantiomers on the different MIPs (and on the non-imprinted polymer, NIP). The adsorption isotherms were analyzed using the affinity spectrum (AS) and the expectation-maximization (EM) methods. The study also involved the theoretical evaluation of the MAPP/enantiomers interactions in the pre-polymer mixture. The EM method predicts mono- and bimodal distribution of affinity binding sites depending upon the polymer analyzed. Apparently, the enantioseparation process depends on relatively small differences in the stabilization of the diasteroisomeric ion-pairs PEA/MAPP complexes on the surface of the polymers.
3. Chiral benzamidinate ligands in rare-earth-metal coordination chemistry
Jochen Kratsch, Corinna M Preuss, Larissa Hartenstein, Paul Benndorf, Peter W Roesky Chemistry . 2012 Nov 5;18(45):14454-63. doi: 10.1002/chem.201202457.
The treatment of the recently reported potassium salt (S)-N,N'-bis-(1-phenylethyl)benzamidinate ((S)-KPEBA) and its racemic isomer (rac-KPEBA) with anhydrous lanthanide trichlorides (Ln = Sm, Er, Yb, Lu) afforded mostly chiral complexes. The tris(amidinate) complex [{(S)-PEBA}(3)Sm], bis(amidinate) complexes [{Ln(PEBA)(2)(μ-Cl)}(2)] (Ln = Sm, Er, Yb, Lu), and mono(amidinate) compounds [Ln(PEBA)(Cl)(2)(thf)(n)] (Ln = Sm, Yb, Lu) were isolated and structurally characterized. As a result of steric effects, the homoleptic 3:1 complexes of the smaller lanthanide atoms Yb and Lu were not accessible. Furthermore, chiral bis(amidinate)-amido complexes [{(S)-PEBA}(2)Ln{N(SiMe(3))(2)}] (Ln = Y, Lu) were synthesized by an amine-elimination reaction and salt metathesis. All of these chiral bis- and tris(amidinate) complexes had additional axial chirality and they all crystallized as diastereomerically pure compounds. By using rac-PEBA as a ligand, an achiral meso arrangement of the ligands was observed. The catalytic activities and enantioselectivities of [{(S)-PEBA}(2)Ln{N(SiMe(3))(2)}] (Ln = Y, Lu) were investigated in hydroamination/cyclization reactions. A clear dependence of the rate of reaction and enantioselectivity on the ionic radius was observed, which showed higher reaction rates but poorer enantioselectivities for the yttrium compound.
