Light-driven [2+2] cycloaddition is the most direct strategy to build tetrasubstituted cyclobutanes, core components of many lead compounds for drug development. Significant advances in the chemoselectivity and enantioselectivity of [2+2] photocycloadditions have been made, but exceptional and tunable diastereoselectivity and regioselectivity (head-to-head versus head-to-tail adducts) is required for the synthesis of bioactive molecules. Here we show that colloidal quantum dots serve as visible-light chromophores, photocatalysts and reusable scaffolds for homo- and hetero-intermolecular [2+2] photocycloadditions of 4-vinylbenzoic acid derivatives, including aryl-conjugated alkenes, with up to 98% switchable regioselectivity and 98% diastereoselectivity for the previously minor syn-cyclobutane products. Transient absorption spectroscopy confirms that our system demonstrates catalysis triggered by triplet–triplet energy transfer from the quantum dot. The precisely controlled triplet energy levels of the quantum dot photocatalysts facilitate efficient and selective heterocoupling, a major challenge in direct cyclobutane synthesis.
Subscribe to Journal
Get full journal access for 1 year
only $13.33 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Crystallographic data for the structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre (CCDC), under deposition number CCDC 1900373 (8). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/. All the other data supporting the findings of this study are available within the article (Figs. 1–4 and Table 1) and its Supplementary Information (Supplementary Tables 1–8, Supplementary Scheme 1, Supplementary Figures 1–4 and Supplementary Sections L and M) or from the corresponding author upon reasonable request.
Alonso, R. & Bach, T. A chiral thioxanthone as an organocatalyst for enantioselective [2+2] photocycloaddition reactions induced by visible light. Angew. Chem. Int. Ed. 126, 4457–4460 (2014).
Maturi, M. M. & Bach, T. Enantioselective catalysis of the intermolecular [2+2] photocycloaddition between 2-pyridones and acetylenedicarboxylates. Angew. Chem. Int. Ed. 53, 7661–7664 (2014).
Hörmann, F. M., Chung, T. S., Rodriguez, E., Jakob, M. & Bach, T. Evidence for triplet sensitization in the visible-light-induced [2+2] photocycloaddition of eniminium ions. Angew. Chem. Int. Ed. 57, 827–831 (2018).
Hu, N. et al. Catalytic asymmetric dearomatization by visible-light-activated [2+2] photocycloaddition. Angew. Chem. Int. Ed. 57, 6242–6246 (2018).
Blum, T. R., Miller, Z. D., Bates, D. M., Guzei, I. A. & Yoon, T. P. Enantioselective photochemistry through Lewis acid-catalyzed triplet energy transfer. Science 354, 1391–1395 (2016).
Dembitsky, V. M. Bioactive cyclobutane-containing alkaloids. J. Nat. Med. 62, 1–33 (2014).
Lee-Ruff, E. & Mladenova, G. Enantiomerically pure cyclobutane derivatives and their use in organic synthesis. Chem. Rev. 103, 1449–1484 (2003).
Tsai, I.-L. et al. New cytotoxic cyclobutanoid amides, a new furanoid lignan and anti-platelet aggregation constituents from Piper arborescens. Planta Med. 71, 535–542 (2005).
Prier, C. K., Rankic, D. A. & MacMillan, D. W. C. Visible light photoredox catalysis with transition metal complexes: applications in organic synthesis. Chem. Rev. 113, 5322–5363 (2013).
Tröster, A., Alonso, R., Bauer, A. & Bach, T. Enantioselective intermolecular [2+2] photocycloaddition Reactions of 2(1H)-quinolones induced by visible light irradiation. J. Am. Chem. Soc. 138, 7808–7811 (2016).
Lei, T. et al. General and efficient intermolecular [2+2] photodimerization of chalcones and cinnamic acid derivatives in solution through visible-light catalysis. Angew. Chem. Int. Ed. 56, 15407–15410 (2017).
Pagire, S. K., Hossain, A., Traub, L., Kerres, S. & Reiser, O. Photosensitised regioselective [2+2]-cycloaddition of cinnamates and related alkenes. Chem. Commun. 53, 12072–12075 (2017).
Gutekunst, W. R. & Baran, P. S. Applications of C–H functionalization logic to cyclobutane synthesis. J. Org. Chem. 79, 2430–2452 (2014).
Poplata, S., Tröster, A., Zou, Y.-Q. & Bach, T. Recent advances in the synthesis of cyclobutanes by olefin [2+2] photocycloaddition reactions. Chem. Rev. 116, 9748–9815 (2016).
Zitt, H., Dix, I., Hopf, H. & Jones, P. Diamino[2.2]paracyclophane, a reusable template for topochemical reaction control in solution. Eur. J. Org. Chem. 2002, 2298–2307 (2002).
Bassani, D. M., Darcos, V., Mahony, S. & Desvergne, J.-P. Supramolecular catalysis of olefin [2+2] photodimerization. J. Am. Chem. Soc. 122, 8795–8796 (2019).
Elacqua, E. et al. A supramolecular protecting group strategy introduced to the organic solid state: enhanced reactivity through molecular pedal motion. Angew. Chem. Int. Ed. 51, 1037–1041 (2012).
Zhang, P. et al. Enantioselective biomimetic total syntheses of katsumadain and katsumadain C. Org. Lett. 14, 162–165 (2012).
Skiredj, A. et al. Spontaneous biomimetic formation of (±)-dictazole B under irradiation with artificial sunlight. Angew. Chem. Int. Ed. 53, 6419–6424 (2014).
Pattabiraman, M., Natarajan, A., Kaliappan, R., Mague, J. T. & Ramamurthy, V. Template directed photodimerization of trans-1,2-bis (n-pyridyl) ethylenes and stilbazoles in water. Chem. Commun. 00, 4542–4544 (2005).
Bučar, D.-K., Sen, A., Mariappan, S. P. S. & MacGillivray, L. R. Cross-photodimerisation of photostable olefins via a three-component cocrystal solid solution. Chem. Commun. 48, 1790–1792 (2012).
Mongin, C., Garakyaraghi, S., Razgoniaeva, N., Zamkov, M. & Castellano, F. N. Direct observation of triplet energy transfer from semiconductor nanocrystals. Science 351, 369–372 (2016).
Huang, Z., Simpson, D. E., Mahboub, M., Li, X. & Tang, M. L. Ligand enhanced upconversion of near-infrared photons with nanocrystal light absorbers. Chem. Sci. 7, 4101–4104 (2016).
Efros, A. L. et al. Band-edge exciton in quantum dots of semiconductors with a degenerate valence band: dark and bright exciton states. Phys. Rev. B 54, 4843 (1996).
Nirmal, M. et al. Observation of the ‘dark exciton’ in CdSe quantum dots. Phys. Rev. Lett. 75, 3728 (1995).
Fritzinger, B., Capek, R. K., Lambert, K., Martins, J. C. & Hens, Z. Utilizing self-exchange to address the binding of carboxylic acid ligands to CdSe quantum dots. J. Am. Chem. Soc. 132, 10195–10201 (2010).
MacGillivray, L. R. et al. Supramolecular control of reactivity in the solid state: from templates to ladderanes to metal−organic frameworks. Acc. Chem. Res. 41, 280–291 (2008).
Ito, Y. Solid-state Organic Photochemistry of Mixed Molecular Crystals Vol. 3 (Dekker, 1999).
Natarajan, A. B., B. R. in Supramolecular Photochemistry. Controlling Photochemical Processes (eds Ramamurthy, V. & Inoue, Y.) 175–228 (Wiley, 2011).
Mongin, C., Moroz, P., Zamkov, M. & Castellano, F. N. Thermally activated delayed photoluminescence from pyrenyl-functionalized CdSe quantum dots. Nat. Chem. 10, 225–230 (2018).
We thank R. Thomson and A. Lee for helpful discussions and T.D. Harris, D. Zee and A. Thorarinsdottir for use of their glove box. Research primarily supported by the Air Force Office of Scientific Research (grant 9550-17-1-0271) (synthesis, photocatalysis and analytical chemistry) and by the Center for Bio-Inspired Energy Science, an Energy Frontier Research Center funded by the US Department of Energy (DOE), Office of Science, Basic Energy Sciences (BES), under Award no. DE-SC0000989 (calculations). C.R.R. thanks the International Institute for Nanotechnology at Northwestern University for a fellowship. This work made use of the IMSERC at Northwestern University, which has received support from the NIH (1S10OD012016-01/1S10RR019071-01A1), Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205), the State of Illinois and the International Institute for Nanotechnology (IIN).
The authors declare no competing interests.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Experimental details, materials and methods, details of the QD catalyst recycling experiment, control studies, description of the transient absorption spectroscopy studies, a kinetic model for the competing formation of syn- and anti-photocycloaddition products, triplet energies of the substrates, cyclic voltammetry, band-edge energies of the CdSe QDs, X-ray crystallographic data, HPLC chromatograms and NMR spectra.
Crystallographic Information File for compound 8, CCDC 1900373.
About this article
Cite this article
Jiang, Y., Wang, C., Rogers, C.R. et al. Regio- and diastereoselective intermolecular [2+2] cycloadditions photocatalysed by quantum dots. Nat. Chem. 11, 1034–1040 (2019) doi:10.1038/s41557-019-0344-4
Colloidally Stable CdS Quantum Dots in Water with Electrostatically Stabilized Weak‐Binding, Sulfur‐Free Ligands
Chemistry – A European Journal (2019)