Crystallization Does It All: An Alternative Strategy for Stereoselective Aza-Henry Reaction

Abstract

An efficient and experimentally straightforward method for the stereoselective synthesis of a variety of β-nitroα-amino carboxylic acids via aza-Henry (nitro-Mannich) reaction of aldimines is disclosed, yielding either anti-or a rarely reported syn-configuration. The reaction operates directly on free glyoxylic acid and generates imine species in situ. Crystallization-controlled diastereoselectivity enables isolation of the target compounds in high enantio-and diastereomeric purities by a simple filtration.

On-off transition and ultrafast decay of amino acid luminescence driven by modulation of supramolecular packing

“…The powder X-ray diffraction (PXRD) patterns of the samples were further examined in order to understand the molecular arrangement of the crystals, which might provide insight into the favorable interactions allowing the crystal fluorescence ( Figure 2 D). The crystal structures of lysine, ornithine, and diaminopropionic acid were previously published ( Chiba et al., 1967 ; Marčeková et al., 2019 ; Williams et al., 2016 ). The crystal structure of diaminobutyric acid was determined by the PXRD pattern obtained in this study CCDC Deposition # 1990651 (see STAR Methods ).…”

On-off transition and ultrafast decay of amino acid luminescence driven by modulation of supramolecular packing

“…The crystal structures of lysine, ornithine and diaminopropionic acid were previously published. [30][31][32] The crystal structure of diaminobutyric acid was determined by the PXRD pattern obtained in this study CCDC Deposition # 1990651 (see Experimental Section). The results revealed the crystal packing of all four samples, allowing molecular inspection of the optical phenomenon.…”

The Stereoselective Nitro-Mannich Reaction in the Synthesis of Active Pharmaceutical Ingredients and Other Biologically Active Compounds

“…Among the recent applications of nitro-Mannich reactions in the synthesis of modified amino acids, an interesting recent example is the stereoselective synthesis of β-nitro-α-amino carboxylic acids, reported by the group of Jakubec (Figure 14A; Marčeková et al, 2019). Aza-Henry reactions of aldimines, yielding either anti-or the more rarely reported syn-configured products were performed leading to products in very high yields and diastereoselectivities.…”

“…The auxiliary could be subsequently removed by hydrogenation on Pd-C to yield the free amino acid. Another useful feature is the fact that the nitroalkane can be used in equimolar amounts, whereas in the majority of processes reported a large excess is used (Marčeková et al, 2019). This method has broad scope, and it even worked well with conformationally constrained substrates, including sterically demanding α,α-disubstituted nitro compounds.…”