DNA‐Based Asymmetric Inverse Electron‐Demand Hetero‐Diels–Alder

Abstract

While artificial cyclases hold great promise in chemical synthesis, this work presents the first example of a DNA‐catalyzed inverse electron‐demand hetero‐Diels–Alder (IEDHDA) between dihydrofuran and various α,β‐unsaturated acyl imidazoles. The resulting fused bicyclic O,O‐acetals containing three contiguous stereogenic centers are obtained in high yields (up to 99 %) and excellent diastereo‐ (up to >99:1 dr) and enantioselectivities (up to 95 % ee) using a low catalyst loading. Most importantly, these results show that the concept of DNA‐based asymmetric catalysis can be expanded to new synthetic transformations offering an efficient, sustainable, and highly selective tool for the construction of chiral building blocks.

New Benchmark in DNA-Based Asymmetric Catalysis: Prevalence of Modified DNA/RNA Hybrid Systems

“… 23 As for the design of the optimum DNA sequence, we took on board the observations made by Roelfes and Feringa who reported the strong influence of small self-complementary DNA sequences on both the enantioselectivity and the reaction rate. 15 They notably observed that 12-mers containing G-tracts lead to the highest levels of selectivity. With this in mind, we started our screening with 5′-GCCAGC S L/D GACCG-3′ ( ODN1 ), where S L/D corresponds to either ( l )-Ser ( S L ) or ( d )-Ser ( S D ).…”

“… 4 Indeed, since the pioneering work of Roelfes and Feringa, 5 who were the first to combine the chirality of the double helical structure of st-DNA with catalytically active metallic cofactors to catalyze a Diels–Alder cycloaddition, 6 the concept of DNA-based asymmetric catalysis (DAC) has been applied to an increasing number of enantioselective carbon–carbon and carbon–heteroatom bond-forming reactions, including Friedel–Crafts alkylations, 7 Michael additions, 8 syn -hydrations, 9 cyclopropanations, 10 fluorinations, 11 the hydrolytic kinetic resolution of epoxides, 12 the hydroamination of nitrostyrene, 13 the photocatalyzed [2 + 2] cycloadditions, 14 and more recently, the inverse electron-demand hetero-Diels–Alder. 15 Despite these achievements, the desire to tailor new DNA-based catalytic systems with improved efficiency, selectivity, and versatility remains an everlasting goal. We report here our efforts toward the development of a DNA/RNA hybrid catalytic system obtained through rational design and rounds of selection, which displays unprecedented levels of selectivity throughout the current DAC repertoire.…”

Harnessing DNA as a Designable Scaffold for Asymmetric Catalysis: Recent Advances and Future Perspectives

“…The enantioselective inverse‐electron‐demand hetero‐Diels‐Alder reaction catalyzed by supramolecular DNA hybrid catalysts was also reported [45] . The enantioselective cycloaddition reaction between azachalcones ( 10a – c , heterodiene) and dihydrofuran ( 11 , dienophile) is shown in Scheme 4.…”

Modular Design of G-Quadruplex MetalloDNAzymes for Catalytic C–C Bond Formations with Switchable Enantioselectivity

“…As a solution, chelate ligands were bound to DNA via covalent or non-covalent interactions. In this way, peroxidase-like reactions and Zn II - and Ce IV -dependent site-specific RNA and DNA cleavage were established. − Roelfes and Feringa pioneered the design of Cu II complexes that bind to double-stranded DNA for enantio­selective transformations such as Diels–Alder reactions, Michael additions, and Friedel–Crafts reactions. − In recent times, also DNA G-quadruplexes were discovered for chiral catalysis, and a first example was reported in 2010 by Moses et al They showcased an enantio­selective Diels–Alder reaction by planar Cu II chelates, non-covalently stacked on a terminal G-quartet . Later, Wang and Li demonstrated Friedel–Crafts reactions, cyclopropanations, and other transformations.…”