Using non-bonding interactions to control photochemical reactions requires an understanding of not only thermodynamics and kinetics of ground state and excited state processes but also the intricate interactions that dictate the dynamics within the system of interest. This review is geared towards a conceptual understanding of how one can control the reactivity and selectivity in the excited state by employing confinement and non-covalent interactions. Photochemical reactivity of organic molecules within confined containers and organized assemblies as well as organic templates that interact through H-bonding and/or cation-carbonyl/cation-π interactions is reviewed with an eye towards understanding supramolecular effects and photocatalysis.
Can photocatalysis be performed without electron or energy transfer? To address this, organo-photocatalysts that are based on atropisomeric thioureas and display lower excited-state energies than the reactive substrates have been developed. These photocatalysts were found to be efficient in promoting the [2+2] photocycloaddition of 4-alkenyl-substituted coumarins, which led to the corresponding products with high enantioselectivity (77-96% ee) at low catalyst loading (1-10 mol%). The photocatalytic cycle proceeds by energy sharing via the formation of both static and dynamic complexes (exciplex formation), which is aided by hydrogen bonding.
Photochemical transformations are a powerful tool in organic synthesis to access structurally complex and diverse synthetic building blocks. However, this great potential remains untapped in the mainstream synthetic community due to the challenges associated with stereocontrol originating from excited state(s). The finite lifetime of an excited state and nearly barrierless subsequent processes present significant challenges in manipulating the stereochemical outcome of a photochemical reaction. Several methodologies were developed to address this bottleneck including photoreactions in confined media and preorganization through noncovalent interactions resulting in stereoenhancement. Yet, stereocontrol in photochemical reactions that happen in solution in the absence of organized assemblies remained largely unaddressed. In an effort to develop a general and reliable methodology, our lab has been exploring non-biaryl atropisomers as an avenue to perform asymmetric phototransformations. Atropisomers are chiral molecules that arise due to the restricted rotation around a single bond (chiral axis) whose energy barrier to rotation is determined by nonbonding interactions (most often by steric hindrance) with appropriate substituents. Thus, atropisomeric substrates are chirally preorganized during the photochemical transformation and translate their chiral information to the expected photoproducts. This strategy, where "axial to point chirality transfer" occurs during the photochemical reaction, is a hybrid of the successful Curran's prochiral auxiliary approach involving atropisomers in thermal reactions and the Havinga's NEER principle (nonequilibrating excited-state rotamers) for photochemical transformations. We have investigated this strategy in order to probe various aspects such as regio-, enantio-, diastereo-, and chemoselectivity in several synthetically useful phototransformations including 6π-photocyclization, 4π-ring closure, Norrish-Yang photoreactions, Paternò-Büchi reaction, and [2 + 2]- and [5 + 2]-photocycloaddition. The investigations detailed in this Account clearly signify the scope of our strategy in accessing chirally enriched products during phototransformations. Simple design modifications such as tailoring the steric handle in atropisomers to hold reactive units resulted in permanently locked/traceless axial chirality in addition to incorporating multiple stereocenters in already complex scaffolds obtained from phototransformation. Further improvements allowed us to employ low energy visible light rather than high energy UV light without compromising the stereoenrichment in the photoproducts. Continued investigations on atropisomeric scaffolds have unraveled new design features, with outcomes that are unique and unprecedented for excited state reactivity. For example, we have established that reactive spin states (singlet or triplet excited state) profoundly influence the stereochemical outcome of an atropselective phototransformation. In general, the photochemistry and photophysics of atropisom...
The efficiency of [2+2] photocycloadditions of 4-alkenylcoumarins was evaluated with various thiourea skeletons to develop thiourea-based catalysts for promoting photochemical reactions. Our results indicate that the excited state chemistry is dependent on the nature of the thiourea catalyst employed to activate the photoactive substrate.Keywords: asymmetric photoreactions; hydrogen bonding photocatalysis; organophotocatalysis; photochirogenesis; thiourea photocatalysis Photochemical transformations are an important class of organic reactions that are often known to generate products with unique stereochemistry.[1] For this reason, chemists have developed strategies that are readily applied in organic synthesis.[2] In recent years, there has been tremendous impetus towards developing enantioselective syntheses of complex strained compounds by light initiated reactions. [1c,2i] In that regard three different catalytic strategies have garnered attention, as they are effective in controlling chemical transformations initiated by light. The first strategy involves photoredox chemistry [3] where a light absorbing sensitizer performs a one electron oxidation or reduction of the reactive substrate leading to a radical anion or a radical cation. As these reactive species are in the ground state, their higher potential enables them to react efficiently to form products. The second strategy involves an energy transfer mechanism [2h,4] where the excited state energy from a light absorbing sensitizer is transferred to the substrate, producing a singlet or a triplet excited state that reacts to form the product. This strategy requires the excited state energy of the sensitizer to be higher than that of the reactive substrate. The third strategy involves an energy sharing mechanism where, upon light excitation, the sensitizer/catalyst and reactant complex (static/dynamic complex) undergo a phototransformation to form the product(s). [5] We have embraced the energy sharing strategy and have utilized thiourea-based catalysts [6] to promote photoreactions with excellent control of product enantioselectivity.[5b] As an example, we showed that 4-alkenylcoumarin 1a underwent a stereoselective [2+2] photocycloaddition to form photoproduct 2a with 94% enantioselectivity with binaphthyl based thiourea catalysts.[5b] Having deciphered the importance of binaphthyl based thiourea catalysts we were interested in evaluating other thiourea skeletons to promote photochemical transformations. We were interested in the role of thioureas not only to achieve high enantioselectivity but also high conversions, as it will increase the type of skeletons that could be employed for controlling photoreactions. In this report we present our findings with six diverse thiourea catalysts 3b-g in promoting the [2+2] photocycloaddition of coumarins 1a and 1b. (Scheme 1). The efficiencies of the new thiourea skeletons were compared to reaction efficiency with our previously established catalyst 3a (prepared in one step from commercially availab...
Mechanistic investigations of the intermolecular [2+2] photocycloaddition of coumarin with tetramethylethylene mediated by thiourea catalysts reveal that the reaction is enabled by a combination of minimized aggregation, enhanced intersystem crossing, and altered excited-state lifetime(s). These results clarify how the excited-state reactivity can be manipulated through catalyst-substrate interactions and reveal a third mechanistic pathway for thiourea-mediated organo-photocatalysis.
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