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Herein, we describe studies showing that Lewis acid co-catalysts can significantly broaden the scope of alkenes that can be incorporated into the photosensitized visible-light De Mayo reaction. Mechanistic studies suggest that the primary benefit of the Lewis acid is not on substrate sensitization but rather on bond-forming steps downstream of energy transfer, highlighting the diverse effects that Lewis acids can have on sensitized photoreactions.

We report the enantioselective [2+2] cycloaddition of simple cinnamate esters, the products of which are useful synthons for the controlled assembly of cyclobutane natural products. This method utilizes a cocatalytic system in which a chiral Lewis acid accelerates the transfer of triplet energy from an excited-state Ir(III) photocatalyst to the cinnamate ester. Computational evidence indicates that the principal role of the Lewis acid cocatalyst is to lower the absolute energies of the substrate frontier molecular orbitals, leading to greater electronic coupling between the sensitizer and substrate and increasing the rate of the energy transfer event. These results suggest Lewis acids can have multiple beneficial effects on triplet sensitization reactions, impacting both the thermodynamic driving force and kinetics of Dexter energy transfer.

The synthesis of unsymmetrical cyclobutanes by controlled heterodimerization of olefins remains a substantial challenge, particularly in an enantiocontrolled fashion. Shown herein is that chiral Lewis acid catalyzed triplet sensitization enables the synthesis of highly enantioenriched diarylcyclobutanes by photocycloaddition of structurally varied 2'-hydroxychalcones with a range of styrene coupling partners. The utility of this reaction is demonstrated through the direct synthesis of a representative norlignan cyclobutane natural product., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The physical, biological, and materials properties of organic compounds are determined by their three-dimensional molecular shape. The development of methods to dictate the stereochemistry of organic reactions has consequently emerged as one of the central themes of contemporary synthetic chemistry. Over the past several decades, chiral catalysts have been developed to control the enantioselectivity of almost every class of synthetically useful transformation. Photochemical reactions, however, are a conspicuous exception. Relatively few examples of highly enantioselective catalytic photoreactions have been reported to date, despite almost a century of research in this field. The development of robust strategies for photochemical enantiocontrol has thus proven to be a long-standing and surprisingly difficult challenge. For the past decade, our laboratory has been studying the application of transition metal photocatalysts to a variety of problems in synthetic organic chemistry. These efforts have recently culminated in the discovery of an effective system in which the activity of a visible light absorbing transition metal photoredox catalyst is combined with a second stereocontrolling chiral Lewis acid catalyst. This dual catalyst strategy has been applied to a diverse range of photochemical reactions; these have included highly enantioselective photocatalytic [2 + 2] cycloadditions, [3 + 2] cycloadditions, and radical conjugate addition reactions. This Account describes the development of the tandem Lewis acid photoredox catalysis strategy utilized in our laboratory. It provides an analysis of the factors that we believe to be particularly important to the success of this seemingly robust approach to photocatalytic stereocontrol. (1) The photocatalysts utilized in our systems are activated by wavelengths of visible light where the organic substrates are transparent, which minimizes the possibility of competitive racemic background photoreactions. (2) The high degree of tolerance that Ru(bpy) 3 and similar octahedral metal polypyridine complexes exhibit toward Lewis acids affords great flexibility in tuning the structure of the stereocontrolling chiral catalyst without perturbing the photoredox properties of the photocatalyst. (3) Synthetic chemists have amassed a substantial understanding of the features that are common in highly successful chiral Lewis acid catalyzed reactions, and these deep, well-validated insights are readily applied to the reactions of a variety of photogenerated intermediates. We hope that the recent success of this and similar dual catalytic systems will provide a useful foundation for the further development of powerful, stereocontrolled photochemical reactions.2+ and similar octahedral metal polypyridine complexes exhibit toward Lewis acids affords great flexibility in tuning the structure of the stereocontrolling chiral catalyst without perturbing the photoredox properties of the photocatalyst. (3) Synthetic chemists have amassed a substantial understanding of the features that are common in highly successful chiral Lewis acid catalyzed reactions, and these deep, well-validated insights are readily applied to the reactions of a variety of photogenerated intermediates. We hope that the recent success of this and similar dual catalytic systems will provide a useful foundation for the further development of powerful, stereocontrolled photochemical reactions.

We report the highly enantioselective addition of photogenerated α-amino radicals to Michael acceptors. This method features a dual-catalyst protocol that combines transition metal photoredox catalysis with chiral Lewis acid catalysis. The combination of these two powerful modes of catalysis provides an effective, general strategy to generate and control the reactivity of photogenerated reactive intermediates.

Control over the stereochemistry of excited-state photoreactions remains a significant challenge in organic synthesis. Recently, it has become recognized that the photophysical properties of simple organic substrates can be altered upon coordination to Lewis acid catalysts, and that these changes can be exploited in the design of highly enantioselective catalytic photoreactions. Chromophore activation strategies, wherein simple organic substrates are activated towards photoexcitation upon binding to a Lewis acid catalyst, rank among the most successful asymmetric photoreactions. Herein, we show that chiral Brønsted acids can also catalyze asymmetric excited-state photoreactions by chromophore activation. This principle is demonstrated in the context of a highly enantio- and diastereoselective [2+2] photocycloaddition catalyzed by a chiral phosphoramide organocatalyst. Notably, the cyclobutane products arising from this method feature a trans-cis stereochemistry that is complementary to other enantioselective catalytic [2+2] photocycloadditions reported to date. Lewis acids have recently been shown to enable stereocontrol in photochemical cycloadditions, a difficult task due to the reactivity of excited-state compounds. Here the authors show that chiral Brønsted acids are competent chromophore activators in [2+2] cycloadditions, forming diastereomers disfavored in similar Lewis acid catalyzed photochemical reactions. [ABSTRACT FROM AUTHOR]

A method for intermolecular [3+2] cycloaddition between aryl cyclopropyl ketones and alkenes involving the combination of Lewis acid and photoredox catalysis is reported. In contrast to other more common methods for [3+2] cycloaddition, these conditions operate using a broad range of both electron-rich and electron-deficient reaction partners. The critical factors predicting the success of these reactions is the redox potential of the cyclopropyl ketone and the ability of the alkene to stabilize a key radical intermediate. [ABSTRACT FROM AUTHOR]

The synthesis of unsymmetrical cyclobutanes by controlled heterodimerization of olefins remains a substantial challenge, particularly in an enantiocontrolled fashion. Shown herein is that chiral Lewis acid catalyzed triplet sensitization enables the synthesis of highly enantioenriched diarylcyclobutanes by photocycloaddition of structurally varied 2′-hydroxychalcones with a range of styrene coupling partners. The utility of this reaction is demonstrated through the direct synthesis of a representative norlignan cyclobutane natural product. [ABSTRACT FROM AUTHOR]

The article presents a new means for the catalyzed formation of Lewis acid, as well as cycloaddition of a differently inaccessible N-nosyl nitrones. These nitrones have the ability to generate 1,2-isoxazolidines that can be deprotected in meek considerations. Details of the study are also explained and provided for in the article.

Relatively few catalytic systems are able to control the stereochemistry of electronically excited organic intermediates. Here we report the discovery that a chiral Lewis acid complex can catalyze triplet energy transfer from an electronically excited photosensitizer.We applied this strategy to asymmetric [2 + 2] photocycloadditions of 2′-hydroxychalcones, using tris(bipyridyl) ruthenium(II) as a sensitizer. A variety of electrochemical, computational, and spectroscopic data rule out substrate activation by means of photoinduced electron transfer and instead support a mechanism in which Lewis acid coordination dramatically lowers the triplet energy of the chalcone substrate.We expect that this approach will enable chemists to more broadly apply their detailed understanding of chiral Lewis acid catalysis to stereocontrol in reactions involving electronically excited states. [ABSTRACT FROM AUTHOR]

The first highly enantioselective intermolecular addition of photogenerated α‐amino radicals to Michael acceptors is reported. [ABSTRACT FROM AUTHOR]