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

Tadashi Ema, Takayuki Yamasaki, Sagiri Watanabe, Mahoko Hiyoshi, Kazuto Takaishi

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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).

Original languageEnglish
JournalJournal of Organic Chemistry
DOIs
Publication statusAccepted/In press - Jan 1 2018

ASJC Scopus subject areas

  • Organic Chemistry

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