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 co-catalytic 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 co-catalyst 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.

Methods that enable the direct C−H alkoxylation of complex organic molecules are significantly underdeveloped, particularly in comparison to analogous strategies for C−N and C−C bond formation. In particular, almost all methods for the incorporation of alcohols by C−H oxidation require the use of the alcohol component as a solvent or co‐solvent. This condition limits the practical scope of these reactions to simple, inexpensive alcohols. Reported here is a photocatalytic protocol for the functionalization of benzylic C−H bonds with a wide range of oxygen nucleophiles. This strategy merges the photoredox activation of arenes with copper(II)‐mediated oxidation of the resulting benzylic radicals, which enables the introduction of benzylic C−O bonds with high site selectivity, chemoselectivity, and functional‐group tolerance using only two equivalents of the alcohol coupling partner. This method enables the late‐stage introduction of complex alkoxy groups into bioactive molecules, providing a practical new tool with potential applications in synthesis and medicinal chemistry.

The synthesis of unsymmetrical cyclobutanes by controlled heterodimerization of olefins remains a substantial challenge, particularly in an enantiocontrolled fashion. Here we show 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. We demonstrate the utility of this reaction through a direct synthesis of a representative norlignan cyclobutane natural product.

The synthesis of unsymmetrical cyclobutanes by controlled heterodimerization of olefins remains as ubstantial challenge,particularly in an enantiocontrolled fashion. Shown herein is that chiral Lewis acid catalyzedt riplet sensitization enables the synthesis of highly enantioenriched diarylcyclobutanes by photocycloaddition of structurally varied 2'-hydroxychalcones with arange of styrene coupling partners.The utility of this reaction is demonstrated through the direct synthesis of arepresentative norlignan cyclobutane natural product.

Methods that enable the direct C−H alkoxylation of complex organic molecules are significantly underdeveloped, particularly in comparison to analogous strategies for C−N and C−C bond formation. In particular, almost all methods for the incorporation of alcohols by C−H oxidation require the use of the alcohol component as a solvent or co‐solvent. This condition limits the practical scope of these reactions to simple, inexpensive alcohols. Reported here is a photocatalytic protocol for the functionalization of benzylic C−H bonds with a wide range of oxygen nucleophiles. This strategy merges the photoredox activation of arenes with copper(II)‐mediated oxidation of the resulting benzylic radicals, which enables the introduction of benzylic C−O bonds with high site selectivity, chemoselectivity, and functional‐group tolerance using only two equivalents of the alcohol coupling partner. This method enables the late‐stage introduction of complex alkoxy groups into bioactive molecules, providing a practical new tool with potential applications in synthesis and medicinal chemistry.