Enantioselective Diels–Alder Reactions with G‐Quadruplex DNA‐Based Catalysts

Abstract

Deoxyribonucleic acid (DNA) is the genetic material of living organisms. In the past, double-stranded DNA (dsDNA) with its ubiquitous architecture has not been regarded as a catalytic species, since the duplex structure precludes the formation of catalytically competent tertiary structures.[1] To date, although no naturally occurring catalytic DNA has been reported, DNA for nonbiological applications has aroused much interest in chemists for applications in areas such as catalysis, encoding, and stereocontrol.[2] Among these applications, a series of DNA-based asymmetric catalysis have been developed, which use a hybrid catalyst composed of dsDNA and a copper(II) complex.[3] This same strategy was later applied to G-quadruplex DNA (G4DNA) and modest enantioselectivities in the Diels-Alder (D-A) reaction were obtained.[4] Very recently, a G4DNA metalloenzyme composed of G4DNA and copper(II) ions has been reported to be able to catalyze an enantioselective Friedel-Crafts reaction. [5] This biology/chemistry interface is an attractive area of research and awaits further extensive exploration. Herein, we report an enantioselective D-A reaction achieved through the use of human telomeric G4DNA-based catalysts. We show that the absolute configuration of the products can be reversed when the conformation of the G4DNA is switched from antiparallel to parallel. Furthermore, both the reaction rate and the enantioselectivity of the reaction were found to be dependent on the DNA sequence.The D-A reaction is an important carbon-carbon bond forming reaction in organic synthesis. In the past few decades, it has received much attention in the development of innovative catalytic strategies to control the creation of the new carbon-carbon bonds and stereocenters. Among those strategies, biological molecules have been viewed as interesting and promising catalysts.[6] Herein, human telomeric G4DNA (ODN-1, 5'-G 3 (T 2 AG 3 ) 3 -3') was selected owing to its tunable conformation. As an initial attempt, a model D-A reaction [7] between aza-chalcone (1 a) and cyclopentadiene (2) was chosen to probe the catalytic performance of ODN-1. We found that ODN-1 alone in its antiparallel conformation [8] could promote the D-A reaction and the enantiomeric excess of the endo isomer of product 3 a is 17 % (Table 1, entry 2).The enantioselectivity of the ODN-1 promoted D-A reaction is significantly higher than that of the uncatalyzed reaction (Table 1, entry 2 vs. entry 1), which suggests that ODN-1 might function as an enantioselective catalyst for the D-A reaction.We assembled a complex between Cu(NO 3 ) 2 and ODN-1 (ODN-1-Cu 2+ ) and tested its ability to enantioselectively catalyze the D-A reaction. ODN-1-Cu 2+ provides a significant enhancement in the reaction rate ( entry 3). We also observed an excellent diastereoselectivity for product 3 a (endo/exo of 98:2) and a good enantioselectivity (74 % ee). These results suggest that ODN-1-Cu 2+ can serve as a potent catalyst, providing stereoselectivity and enhancement in reaction rates. To furthe...

Regioselective Heck reaction catalyzed by Pd nanoparticles immobilized on DNA-modified MWCNTs

“…These approaches employing aryl triflate substrate and numerous phosphine backbone ligands such as amide-based phosphite-oxazolines, 11 atropisomeric P,O-ligands, 16 benzylically substituted P,Nligands, 17 and diphosphine-oxazoline ferrocenyl 18 in presenting of palladium salts. [31][32][33][34][35][36][37][38] This molecule has several properties that make it a very promising scaffold for designing a hybrid catalyst, which is chemically stable and commercially available natural DNA is inexpensive. However, the main drawback of this substrate is the easy hydrolysis of triflate, limiting its application in the presence of water.…”

DNA-based hybrid catalysis

“…without ligand. Using human telomeric G-quadruplex sequences up to 75% ee was obtained in the catalyzed enantioselective Friedel-Crafts alkylation and up to 74% ee in the Diels-Alder reactions [22,23 ]. The enantiomeric outcome of the reaction could be switched by addition of either Na + or K + ions, which was ascribed to the formation of either antiparallel or hybrid G-quadruplex structures, respectively [24].…”

Enantioselectively-Catalyzed Reactions with (E)-2-Alkenoyl-pyridines, TheirN-Oxides, and the Corresponding Chalcones

“…reaction between 1 and cyclopentadiene was faced testing human telomeric G4DNA of composition [5′-G 3 (T 2 AG 3 ) 3 Table 21 show that, unexpectedly, the organic ligand 2,2′-bipyridine (XXXIVa) is not necessary and the best result, in terms of conversion, diastereo-and enantioselectivity, is obtained when G4DNA itself behaves as organic ligand (Table 21, entries 9 and 12). Furthermore, the [h- 66 Given the results obtained with catalysts between Gquadruplex as chiral source and the Cu(II) complexes of the above-reported achiral ligands, two points were inferred in details. Starting from the human telomeric G4 sequence (h-Tel), several nucleobase substitution experiments were performed to investigate the influence on stereoselectivity of the D.A.…”