Synthesis of a Sterically Crowded Atropisomeric 1,8-Diacridylnaphthalene for Dual-Mode Enantioselective Fluorosensing

Abstract

An efficient synthetic route to a sterically crowded 1,8-diheteroarylnaphthalene-derived enantioselective fluorosensor that operates in two different detection modes utilizing fluorescence lifetime and intensity has been developed. Screening of palladium-catalyzed Negishi, Kumada, Suzuki, Hiyama, and Stille coupling methods showed that the latter affords highly congested 1,8-diarylnaphthalenes in superior yields. Despite severe steric hindrance, axially chiral 1,8-bis(3-(3',5'-dimethylphenyl)-9-acridyl)naphthalene, 1, was obtained in 68% yield from 1,8-dibromonaphthalene, 14, and 3-(3',5'-dimethylphenyl)-9-tributylstannylacridine, 13, via two consecutive Stille cross-coupling steps using tetrakis(triphenylphosphine)palladium(0) as catalyst in the presence of copper(II) oxide. The preparation of 1 involved formation of 4-(3',5'-dimethylphenyl)-2-chlorobenzoic acid, 7, through microwave-assisted Suzuki coupling of 4-bromo-2-chlorobenzoic acid, 10, and 3,5-dimethylphenylboronic acid, 11, followed by regioselective amination with aniline and acridine ring construction in phosphorus oxybromide. Lithiation, subsequent treatment with trimethylstannyl chloride, and Stille cross-coupling then completed the five-reaction sequence providing 1 in 57% overall yield. The enantiomers of 1 were separated by semipreparative HPLC on a (R,R)-Whelk-O 1 column and successfully employed in enantioselective fluorosensing of N-t-Boc-protected serine, 20, glutamine, 22, proline, 23, and 2-hydoxy-2-methylsuccinic acid, 21. Fluorescence titration experiments with 23 revealed that both static and dynamic quenching occur with distinctive enantioselectivity. Addition of (R)-23 to a solution of (+)-1 in acetonitrile resulted in stronger fluorescence quenching than titration with the (S)-enantiomer of 23. The fluorescence lifetime, tau, of 1 was determined as 18.8 ns and steadily decreased to 7.5 and 6.8 ns in the presence of 0.1 M of (S)-23 and (R)-23, respectively.

Crystal structure of 1,8-dibenzoyl-2,7-diphenoxynaphthalene

“…Peri-substituted naphthalenes have received much attention as characteristic-structured aromatic-ring-core compounds for a variety of functional materials (Mei et al, 2006;Shinamura et al, 2010;Jiang et al, 2010;Shao et al, 2014). For example, rylene derivatives are fluorophores well known for their exceptional photochemical stability and high fluorescence quantum yields (Wü rthner et al, 2004;Jiao et al, 2009), and employed in solar cells (Shibano et al, 2009), laser dyes (Gvishi et al, 1993), organic light-emitting field-effect transistors (Seo et al, 2013) and optical switches (Oneil et al, 1992).…”

Crystal Structure Study on Non-Coplanarly Organized Accumulating Aromatic Rings Molecules: Spatial Organization of <i>C</i>,<i>C</i>,<i>N</i>-Triaryl Substituted Imines

“…Non-coplanarly accumulated aromatic-rings compounds, e.g., biphenyls and binaphthyls, have been demonstrated as unique building blocks in construction for many functional materials such as molecular catalysis and functional polymers [1][2][3][4][5][6][7][8][9][10][11][12]. Thus, minute spatial structural characterization of these compounds [13][14][15][16] has attracted attention of the chemists in the wide-range of organic molecular science and polymer materials fields.…”

Head-to-tail square-shaped cyclic hydrogen bonds leading to dimeric aggregates: 1,8-dibenzoyl-2,7-dihydroxynaphthalene and a comparison with its analogous benzoylnaphthalene

“…optical and electronic properties, and the applications based on the properties for optically active polymers and catalysts, organic fluorescent dyes and light-emitting diodes (Alfonso et al, 2007;Gasparrini et al, 2008;Zhang et al, 2011). Peri-substituted naphthalenes have also received much attention as characteristic structured aromatic core compounds for a variety of functional materials (Mei et al, 2006;Shinamura et al, 2010;Jiang et al, 2010). Therefore, structural analyses have been actively performed (Gore et al, 1980;Cohen et al, 2004;Jing et al, 2005).…”