Bidentate Schiff bases derived from (S)-α-methylbenzylamine as chiral ligands in the electronically controlled asymmetric addition of diethylzinc to aldehydes

Abstract

A group of bidentate Schiff bases derived from enantiomerically pure (S)--methylbenzylamine was synthesized. Crystal structure was determined for three compounds. Schiff bases were used as chiral ligands in the asymmetric addition of Et2Zn to aldehydes. The obtained enantioselectivity was e.e.=8-94% depending on the substrate and the best was observed for (S,E)-2-(1-(1-phenylethylimino)-ethyl)phenol. The enantioselectivity increase was connected with the substituent-induced electronic effects in the substrate molecules. Molecular modeling resulted in the models of the 3D structures of Zn-Zn complex catalysts containing investigated Schiff bases, which were consistent with the reported chirality of the addition product and explained observed e.e. The presented transition state models allow explaining the change of the absolute configuration of diethylzinc addition product in the case of using ortho-substituted aldehydes.

Chiroptical Inversion Induced by Rotation of a Carbon–Carbon Single Bond: An Experimental and Theoretical Study

“…Among them, the conformer s -1c is preferred over s -1a and s -1b by 2.25 and 1.41 kcal/mol, respectively. The computed conformer of lowest energy is in good agreement with the known single-crystal X-ray diffraction structure (Figure ) and Smith’s conformational analysis as well …”

“…Comparison of (left) the computed structure for the most stable conformer s -1c in vacuum obtained at the B3LYP/6-311++G** level of theory and (right) the reported single-crystal structure of s - 1 from ref .…”

Ease to Challenges in Achieving Successful Synthesized Schiff Base, Chirality, and Application as Antibacterial Agent

“…However, recently, the extensive applicability of this transformation was reduced due to the unobtainability of appropriate catalysts for assigning a certain stereochemistry to the newly made stereogenic centers [22]. 2 BioMed Research International diethylzinc to aldehyde as shown in Scheme 6 [24]. They achieved an enantiomer excess (e.e) of 8 to 94% based on the substrate, and the finest was observed for (S, e)-2-(1-(1-phenylethylimino)-ethyl) phenol [24].…”

“…2 BioMed Research International diethylzinc to aldehyde as shown in Scheme 6 [24]. They achieved an enantiomer excess (e.e) of 8 to 94% based on the substrate, and the finest was observed for (S, e)-2-(1-(1-phenylethylimino)-ethyl) phenol [24]. Additionally, chiral Schiff bases with substituent were reported to have strong influence on a catalyst's effectiveness, enantioselectivities, and reactiv-ities [14,25].…”

“…use of m-chloro, p-chlorobenzaldehyde, and p-bromobenzaldehyde gave very considerable higher enantiomeric excesses of addition products (e:e: = 94%, 53%, and 96%, respectively, in Table 2: entries 6-8). They observed that the presence of electron-withdrawing substituent in the substrates which initiated an increased Lewis acidity on the carbon atom of the carbonyl group was accountable for increased substrate's reactivity [24]. In vitro cytotoxicity screening revealed that the metal complexes had substantial cytotoxic results higher than that of cisplatin, against three cancer cell lines breast (HepG2), cervical carcinoma (MDA-MB231), and lung (A549) cancer cell lines.…”