1‐(α‐Aminobenzyl)‐2‐naphthol: A New Chiral Auxiliary for the Synthesis of Enantiopure α‐Aminophosphonic Acids

Abstract

A new diastereoselective synthesis of alpha-aminophosphonates has been developed, based on the reaction, in the presence of trifluoroacetic acid, of trialkyl phosphites with chiral imines derived from (R)- or (S)-1-(alpha-aminobenzyl)-2-naphthol. The reaction proceeds at room temperature in toluene with high diastereoselectivity. The major diastereomer can be separated by crystallization from an appropriate solvent. The relative configuration of both chiral centers of the major diastereomer was determined by single-crystal X-ray structure analysis. The desired alpha-aminophosphonic acids can be obtained in enantiopure form by treatment of the corresponding diastereomers with HCl.

Selective Synthesis and Structural Confirmation of 1,3‐Oxazines and Schiff Bases with Controllable Substitution Patterns

“…This type of cyclic and Schiff base product formation of the Betti base has been earlier referred to as ring-chain tautomerism. [20][21][22][23][24] As described earlier, [12][13][14][15][16][17][18][19][20][21][22][23][24] the separation and purification in racemic Betti-base syntheses are very difficult. Our current tactic of using ammonium acetate in the conventional approach enabled us to successfully isolate stable oxazines (ring) and Schiff bases (open chain) that contain two identical or two different aryl substituents.…”

“…The condensation of b-naphthol, benzaldheyde, and ammonia in alcoholic solution at room temperature for several days [12,13] results in (E)-[(1-phenylmethyl(phenylmethylideneamino)]naphth-2-ol (imine formation), which exists in tautomeric equilibrium with two diasteromeric trans-and cis-2,4-diphenyl-2,3-dihydro-3H-naphthoA C H T U N G T R E N N U N G [1,2-e]-1,3-oxazines formed by tautomeric N,O proton transfer in solution phase. Further, in the case of racemic Betti-base synthesis, separation and purification of enantiomers are not straightforward [14][15][16][17][18][19][20][21][22][23][24] and very few reactions similar to Bettis approach have been reported so far in the literature.…”

Stereoselective Synthesis of α-Aminophosphonic Acids Using the Betti Base as Chiral Auxiliary

“…up to 84%). 13 When racemic imine 1a was used in the reaction with triethyl phosphite, a major diastereomer of phosphonate (9a) was obtained after recrystallization of the diastereomerically enriched product from toluene with 78% yield. This result allows us to synthesize enantiopure aminophosphonates, as was carried out by reaction of enantiopure imines 1a,f,g with triethyl phosphite and TFA.…”

Multicomponent reaction in deep eutectic solvent for synthesis of substituted 1-aminoalkyl-2-naphthols

“…This MCR provides a valuable framework for obtaining compounds that have several interesting biological applications, such as antibacterial, hypotensive, and bradycardiac activities [12], as well as pharmacological properties [13,14]. Furthermore, there is growing interest in Betti bases as chiral inductors or chiral precursors for asymmetric synthesis of a-aminophosphonic acids [15].…”