Cooperative Al(Salen)-Pyridinium Catalysts for the Asymmetric Synthesis of trans-Configured β-Lactones by [2+2]-Cyclocondensation of Acylbromides and Aldehydes: Investigation of Pyridinium Substituent Effects

Abstract

The trans-selective catalytic asymmetric formation of β-lactones constitutes an attractive surrogate for anti-aldol additions. Recently, we have reported the first catalyst which is capable of forming trans-β-lactones with high enantioselectivity from aliphatic (and aromatic) aldehyde substrates by cyclocondensation with acyl bromides. In that previous study the concepts of Lewis acid and organic aprotic ion pair catalysis were combined in a salen-type catalyst molecule. Since a pyridinium residue on the salen periphery is essential for high trans- and enantioselectivity, we were interested in the question of whether substituents on the pyridinium rings could be used to further improve the catalyst efficiency, as they might have a significant impact on the effective charges within the heterocycles. In the present study we have thus compared a small library of aluminum salen/bispyridinium catalysts mainly differing in the substituents on the pyridinium residues. As one result of these studies a new catalyst was identified which offers slightly superior stereoselectivity as compared to the previously reported best catalyst. NBO calculations have revealed that the higher stereoselectivity can arguably not be explained by the variation of the effective charge.

Asymmetric Catalysis Using Chiral Salen–Metal Complexes: Recent Advances

“…The reaction is restricted to acyl bromides; acyl chlorides do not participate in this process at −70 °C. A later study describes a series of aluminum–salen bispyridinium catalysts similar to 161 but differing in the presence of substituents on the pyridinium rings . These catalysts give only slightly improved stereoselectivity compared to 161 .…”

β-Lactones: A Novel Class of Ca2+-Independent Phospholipase A2 (Group VIA iPLA2) Inhibitors with the Ability To Inhibit β-Cell Apoptosis

“…For β-lactones, the ratio of the peak integrations corresponding to methinic proton of either C-3 or C-4 indicated a ratio of trans/cis diastereomers varying from 9:1 to 7:3. trans β-Lactones were obtained in excess being thermodynamically more stable than their counterparts cis products, and their geometry was determined by 1 H NMR based on the chemical shifts reported in literature for similar compounds. In accordance with the literature data, characteristic peaks for 3-CH and 4-CH are reported at 3.2 and 4.2 ppm, respectively, for trans βlactones, 39 whereas the corresponding chemical shifts for cis β-lactones are reported at 3.6 and 4.5 ppm, respectively. 40 The trans and cis diastereomers of 9d, e, f, j, and k were separated by column chromatography.…”

Synthesis of Long‐Chain β‐Lactones and Their Antibacterial Activities against Pathogenic Mycobacteria

“…Furthermore, from the lead of the initial screening, VM001, the two racemic mixtures of cis ‐VM001 and trans ‐VM001, namely VM007 and VM008, respectively, were successfully isolated by column chromatography (Scheme B). The geometry of these isolated stereoisomers was determined by 1 H NMR spectroscopy based on the chemical shifts of the characteristic peaks of α‐ and β‐protons that were compared with the corresponding reference peaks in the literature . The racemic mixture of trans ‐VM009, assigned as VM013, was also chromatographically isolated in pure form and tested.…”