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Cross-Coupling Approach to an Array of Macrocyclic Receptors Functioning as Chiral Solvating Agents

Author:
Ema, Tadashi, Yamasaki, Takayuki, Watanabe, Sagiri, Hiyoshi, Mahoko, Takaishi, Kazuto
Source:
Journal of organic chemistry 2018 v.83 no.18 pp. 10762-10769
ISSN:
1520-6904
Subject:
Suzuki reaction, crystal structure, enantioselectivity, hydrogen bonding, moieties, nuclear magnetic resonance spectroscopy, organic compounds, receptors
Abstract:
Chiral macrocyclic receptors 1 with multiple hydrogen-bonding sites in the cavity were synthesized and used as NMR chiral solvating agents (CSAs). The Suzuki–Miyaura cross-coupling reaction gave rapid access to a series of variants 1b–p of unsubstituted parent compound 1a. Among them, 1d with the 4-cyanophenyl group at the 3,3′-positions of the binaphthyl moiety was the most excellent CSA for a benchmark analyte compound, 2-chloropropionic acid (CPA); both of the quartet and doublet signals of CPA were split most completely in CDCl₃. Binding constants (Kₐ) determined in CDCl₃ by NMR titrations indicated that (R)-1d was the most enantioselective (Kₐ(S)/Kₐ(R) = 5.4). Interestingly, the Kₐ value of (R)-1d for (S)-CPA (5900) was greater than that of (R)-1a for (S)-CPA (3080), which strongly suggests an attractive interaction between the 4-cyanophenyl group of (R)-1d and (S)-CPA. The X-ray crystal structure of 1d indicates that one of the two H atoms meta to the cyano group is directed toward the cavity. DFT calculations suggested that this H atom of the 4-cyanophenyl group of (R)-1d forms a weak hydrogen bond with the Cl atom of (S)-CPA (C–H···Cl–C hydrogen bond).
Agid:
6146160