Abstract
The precise site-specific positioning of metal–ligand complexes on various DNA structures through covalent linkages has gained importance in the development of hybrid catalysts for aqueous-phase homogeneous catalysis. Covalently modified double-stranded and G-quadruplex DNA-based hybrid catalysts have been investigated separately. To understand the role of different DNA secondary structures in enantioselective Friedel–Crafts alkylation, a well-known G-quadruplex-forming sequence was covalently modified at different positions. The catalytic performance of this modified DNA strand was studied in the presence and absence of a complementary DNA sequence, resulting in the formation of two different secondary structures, namely duplex and G-quadruplex. Indeed, the secondary structures had a tremendous effect on both the yield and stereoselectivity of the catalyzed reaction. In addition, the position of the modification, the topology of the DNA, the nature of the ligand, and the length of the linker between ligand and DNA were found to modulate the catalytic performance of the hybrid catalysts. Using the optimal linker length, the quadruplexes formed the (−)-enantiomer with up to 65% ee, while the duplex yielded the (+)-enantiomer with up to 62% ee. This study unveils a new and simple way to control the stereochemical outcome of a Friedel–Crafts reaction.
Highlights
The Friedel–Crafts reaction was first reported in 1877 [1,2]
While the classical Friedel–Crafts reactions were performed under strictly anhydrous conditions, in recent years numerous attempts were made to expand this reaction to aqueous media [6]
The dU12-modified sequences were combined with a complementary DNA sequence to fold into the dsDNA, which was used as a catalyst in combination with Cu(II) for the same enantioselective Friedel–Crafts alkylation
Summary
The Friedel–Crafts reaction was first reported in 1877 [1,2]. Since it has become one of the most versatile methods for the formation of carbon–carbon bonds, and enantioselective Friedel–Crafts alkylation reactions have gained particular importance [3,4,5]. The concept of DNA-based hybrid catalysts was first reported by Roelfes and Feringa in 2005, where the combination of a double-stranded (ds) DNA and a Cu(II)-complex covalently bound to an intercalating moiety was tested [17] Since this approach has been successfully expanded to various enantioselective reactions, such as Diels–Alder reactions [17,18,19,20,21], inverse electron-demand hetero-Diels–Alder reactions [22], Friedel–Crafts alkylations [23,24,25,26,27], Michael additions [28,29,30], fluorinations [31], syn-hydrations [32], and metal–organic reactions [33]. We report a direct comparison of G-quadruplex and duplex DNA-based hybrid catalysts, formed by covalent attachment of different bpy-linker constructs to the quadruplex forming sequences and their application on an enantioselective Friedel–Crafts alkylation. While quadruplexes preferentially formed the (−)-enantiomer with up to 65% ee, the best duplex yielded the (+)-enantiomer with up to 62% ee
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