Chiral Recognition and Kinetic Resolution of Aromatic Amines via Supramolecular Chiral Nanocapsules in Nonpolar Solvents

Abstract

Herein we report the first example of chiral recognition and kinetic resolution of aromatic amine guests using supramolecular nanocapsules assembled from cyclodextrin derivatives in nonpolar media. With these nanocapsules, an extremely high chiral recognition of 1-(1-naphthyl)ethylamine (1) in cyclohexane was achieved, with a binding selectivity of up to 41 for (S)-1 over (R)-1. In addition, kinetic resolution of 1 through enantioselective N-acylation was accomplished with an enantiomeric excess of up to 91%.

Kinetic resolution of primary amines via enantioselective N-acylation with acyl chlorides in the presence of supramolecular cyclodextrin nanocapsules

“…The X-ray crystalline structure showed that the 4i molecule was included within the cavity of the TIPS-β-CD dimer in a similar fashion to a TIPS-β-CD-(S)-1-(1-naphthyl)ethylamine 6 or TIPS-β-CD-pyrene 10 complex previously reported (Figure 3). Interestingly, both the carbonyl oxygen and chlorine atoms of the 1-naphthoyl chloride molecule formed hydrogen bonds with the 3-OH group of the upper and lower TIPS-β-CDs, respectively (the O···O and Cl···O distances are 2.68 and 3.14 Å, respectively).…”

“…Similar to our recent study using acid anhydride as an acylation reagent, 6 cyclohexane was chosen as the solvent, in which the supramolecular TIPS--CD nanocapsule showed high chiral recognition towards 1 (Table 1, entry 1). A mixture of primary amines 1-3, TIPS--CD (5.0 equiv), and triethylamine (1.0 equiv) in cyclohexane was stirred for 1 h to reach complexation equilibrium.…”

“…= 7%, ee = 91%, s = 23; conv. = 49%, ee = 75, s = 15), 6 suggesting that the supramolecular CD nanocapsule can be applied to the KR of primary amines with not only acid anhydride, but also with more reactive acyl chlorides. 7 To the best of our knowledge, this is the first report of the enantioselective N-acylation of a primary amine with acyl chloride as an acylation reagent.…”

“…More recently, we reported the high chiral recognition and KR of primary amines utilizing a supramolecular chiral nanocapsule assembled by 6-Otriisopropylsilylated -cyclodextrin (TIPS--CD) in nonpolar solvents. 6 In particular, the KR of racemic 1-(1-naphthyl)ethylamine (1-NEA) was achieved via enantioselective N-acylation with benzoic anhydride in the presence of this supramolecular chiral nanocapsule with an enantiomeric excess of up to 91%. This result implies that the supramolecular cyclodextrin nanocapsule can potentially function as a powerful tool for the KR of highly reactive chemical species including primary amines.…”

Visible chiral discrimination via macroscopic selective assembly

“…Cyclodextrins, cyclic oligomers of D-glucopyranose units with a conical chiral cavity, have chirality sensing ability through host-guest interactions [40][41][42] . Consequently, cyclodextrins are employed in various matrixes for applicable enantiomeric selectivity and separation, e.g., microspheres, nanochannels, electrodes, and the stationary phase of columns [43][44][45][46] .…”