Synthesis and Stereochemical Characterization of a Novel Chiral α-Tetrazole Binaphthylazepine Organocatalyst

Abstract

A novel α-tetrazole-substituted 1,1′-binaphthylazepine chiral catalyst has been synthesized and its absolute configuration has been determined by DFT computational analysis of the vibrational circular dichroism (VCD) spectrum of its precursor. The VCD analysis, carried out through the model averaging method, allowed to assign the absolute configuration of a benzylic stereocenter in the presence of a chiral binaphthyl moiety. The 1,1′-binaphthylazepine tetrazole and the nitrile its immediate synthetic precursor, have been preliminarily tested as chiral organocatalysts in the asymmetric intramolecular oxa-Michael cyclization of 2-hydroxy chalcones for the synthesis of chiral flavanones obtaining low enantioselectivity.

Catalytic Tetrazole Synthesis via [3+2] Cycloaddition of NaN3 to Organonitriles Promoted by Co(II)-complex: Isolation and Characterization of a Co(II)-diazido Intermediate

“…These unnatural heterocyclic compounds have largely manifested their applications in medicinal chemistry and pharmaceutical science. − Due to the longer biodisponibility, the tetrazole moiety increases the activity of the drug without affecting the active pharmaceutical ingredient. Furthermore, the acidic nature of 5-substituted 1H-tetrazoles renders them to act as bioisosteric replacements of carboxylic acids. − A large variety of tetrazole fragments containing drug molecules have been reported to date. − Due to their high energy properties, tetrazole derivatives also found their applications as potential explosives and in the manufacturing of high-energy materials. − Furthermore, tetrazole derivatives are used for the preparation of ligands for various kinds of coordination complexes. − These nitrogen-rich heterocyclic compounds are also extensively used as effective organocatalysts. − …”

5,5,7,7-Tetrametyl-6,7-dihydro-5H-dibenzo[c,e]azepine

“…Dibenz[c,e]azepines constitute an important class of compounds widely employed as chiral or pro-chiral scaffolds for the construction of chiral catalysts for asymmetric synthesis or probes for chiral molecular recognition. In particular, 1,1 -binaphthylazepines have been widely employed as chiral ligands in organometallic catalysis [1][2][3][4][5] and organocatalysis [6][7][8][9][10], while not-atropisomerically stable (i.e., tropos) 1,1 -biphenylazepines have been reported both as structural motifs for the construction of the chiral ligands [9][10][11][12][13][14][15] and as the chiroptical probes for the absolute configuration assignment to the chiral acids [16][17][18][19] and amines [14,20]. In fact, in 1,1 -biphenylazepines the low phenyl-phenyl rotational barrier allows, at room temperature, a free interconversion of the two possible M and P atropisomeric forms.…”