Chiral Aminoalcohols and Squaric Acid Amides as Ligands for Asymmetric Borane Reduction of Ketones: Insight to In Situ Formed Catalytic System by DOSY and Multinuclear NMR Experiments

Abstract

A series of squaric acid amides (synthesized in 66–99% isolated yields) and a set of chiral aminoalcohols were comparatively studied as ligands in a model reaction of reduction of α-chloroacetophenone with BH3•SMe2. In all cases, the aminoalcohols demonstrated better efficiency (up to 94% ee), while only poor asymmetric induction was achieved with the corresponding squaramides. A mechanistic insight on the in situ formation and stability at room temperature of intermediates generated from ligands and borane as possible precursors of the oxazaborolidine-based catalytic system has been obtained by 1H DOSY and multinuclear 1D and 2D (1H, 10/11B, 13C, 15N) NMR spectroscopy of equimolar mixtures of borane and selected ligands. These results contribute to better understanding the complexity of the processes occurring in the reaction mixture prior to the possible oxazaborolidine formation, which play a crucial role on the degree of enantioselectivity achieved in the borane reduction of α-chloroacetophenone.

Design, Synthesis, and Biological Activity of Donepezil: Aromatic Amine Hybrids as Anti-Alzheimerss Drugs

“…The synthesis of DNP-phenylethylamine heterozygous derivatives is described (Scheme .) All the compounds were synthesized according to the previously reported method . The types of bases are discussed, as well as sodium ethoxide, sodium hydride, and triethylamine.…”

“…All the compounds were synthesized according to the previously reported method. 21 The types of bases are discussed, as well as sodium ethoxide, sodium hydride, and triethylamine. As an organic base of the system, the results show that when triethylamine is added to the reaction system as an acidic binder, the reaction can be carried out more efficiently, and when the reaction time is controlled at about 10 h, the yield is improved.…”

Squaramide Tethered Clindamycin, Chloroquine, and Mortiamide Hybrids: Design, Synthesis, and Antimalarial Activity

“…Thus, clindamycin 1 was converted into the known azide 4 following an inversion of configuration at C7 . Then, reduction of the azide furnished the corresponding amine 5 in high yield and treatment with diethyl squarate under basic conditions provided clindamycin-monosquaramide ester 7 in excellent yield . A similar strategy was executed starting from hydroxychloroquine sulfate 2 .…”

“…38 Then, reduction of the azide furnished the corresponding amine 5 in high yield 39 and treatment with diethyl squarate under basic conditions provided clindamycin-monosquaramide ester 7 in excellent yield. 40 A similar strategy was executed starting from hydroxychloroquine sulfate 2. We selected the terminal position of chloroquine for the installation of the linker since biologically active chloroquine analogues were prepared by functionalization at this position.…”