Hydrogen Bonds and Ion Pairs in Enantioselective Photochemistry

Introduction. The field of enantioselective photochemistry has rapidly grown in recent years and many contributions deal with reactions in which a hydrogen bonding or ion pairing interaction is involved. The distinction whether a hydrogen bond or an ion pair is operative is not always trivial and the classification shown below is somewhat arbitrary. Brønsted acids act via a hydrogen-bonded ion pair, but charge separation has frequently been observed. In the current project we rely mainly on two non-covalent motifs that operate to form a given assembly, (1) a two-point hydrogen bond interaction between chiral lactams and a given substrate, and (2) the protonation of a substrate with a chiral Brønsted acid leading to a hydrogen-bonded or a strict ion pair. In both scenarios the species that undergoes an enantioselective transformation is in its excited singlet or triplet state, which is an important distinction to most reactions reported so far.

Summary of the Project. Hydrogen bonds serve as non-covalent interactions to temporarily recruit substrates in an assembly with a photocatalyst. If a complete proton transfer occurs from the acidic catalyst to the substrate, ion pairs will result. The project revolves around two catalyst classes displaying directed bonding motifs and providing a chiral cavity in which enantioselective photochemical reactions can occur. In work package 1 (WP1), a lactam/amide binding motif will be employed, and the catalysts display an azabicyclo[3.3.1]nonan-2-one backbone connected to a single chromophore. In WP2, chiral phosphoric acids will be used, with the option to install one or two photocatalytic entities at the backbone rendering the compounds either C₁ or C₂ symmetric. It is proposed to study mainly reaction classes that rely on hydrogen atom transfer (HAT) or triplet energy transfer. In the latter case, the chromophore within the catalyst is chosen to reach a long-lived, energetically high-lying triplet state enabling the activation of substrate molecules by sensitization. Typical reactions to occur from the triplet state are photocycloaddition reactions at double bonds and photocyclization reactions. HAT processes are suggested to occur via the reactive nπ* triplet of benzophenones and require this chromophore to be attached to the chiral backbone of the catalyst. The HAT can occur already as an enantioselective process differentiating between two enantiotopic positions in the substrate but it can also create a prochiral radical that undergoes an ensuing enantioselective reaction in the confinement of the catalyst-substrate complex. For both processes (energy transfer and HAT) the distance and directionality between the chromophores of catalyst and substrate play a critical role and need to be carefully evaluated by spectroscopic and computational tools.
 

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