Enantioselective photochemistry through Lewis acid-catalyzed triplet energy transfer

Abstract

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.

Figure 1. Enantioselective Catalysis Involving Excited State Organic Intermediates

(A) Prior example of enantioselective Lewis acid catalyzed photoreaction involving direct photoexcitation of a chiral catalyst–substrate complex. (B) Design plan for Lewis acid catalysis of a triplet sensitization reaction.

Figure 2. Scope of the enantioselective catalytic [2+2] cycloaddition of 2′-hydroxychalcones

Data reflect the averaged isolated yields from two reproducible experiments. Diastereomer ratios were determined by ¹H NMR analysis of the unpurified reaction mixture. Enantiomer ratios were determined using chiral SFC or HPLC analysis. See supplementary material for details. ^* Irradiation was conducted using a blue LED lamp instead of a 23 W CFL bulb, 2 h irradiation time. ^† 40 h irradiation time. ^‡Isolated as a 6:1 mixture of regioisomers.

Figure 3. Differentiation of electron transfer and energy transfer pathways

(A) Successful photocycloaddition using an electron-deficient photocatalyst rules out a mechanism involving initial enone photoreduction. (B) Experiments using chemical redox reagents fail to produce [2+2] cycloadducts. (C) UV-activated triplet sensitizer replicates reactivity with similar ee. For full details see the Supplementary Materials.

Figure 4. Computational and experimental evidence for a Lewis acid promoted decrease in triplet energy

(A) Experimental and calculated S₀–T₁ gaps for 2′-hydroxychalcone 2 and its Sc(III) complex. (B) Experimental near-IR emission data for 2′-hydroxychalcone 2 in the absence (black) and presence (red) of Sc(OTf)₃. The emission is partially quenched in the presence of oxygen (blue).