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. 2024 Mar 19;15(1):2462.
doi: 10.1038/s41467-024-46647-4.

Photo-induced intramolecular dearomative [5 + 4] cycloaddition of arenes for the construction of highly strained medium-sized-rings

Min Zhu #  1   2 , Yuan-Jun Gao #  1 , Xu-Lun Huang #  1   2 , Muzi Li  1 , Chao Zheng  3 , Shu-Li You  4   5
Affiliations

Photo-induced intramolecular dearomative [5 + 4] cycloaddition of arenes for the construction of highly strained medium-sized-rings

Min Zhu et al. Nat Commun. .

Abstract

Medium-sized-ring compounds have been recognized as challenging synthetic targets in organic chemistry. Especially, the difficulty of synthesis will be augmented if an E-olefin moiety is embedded. Recently, photo-induced dearomative cycloaddition reactions that proceed via energy transfer mechanism have witnessed significant developments and provided powerful methods for the organic transformations that are not easily realized under thermal conditions. Herein, we report an intramolecular dearomative [5 + 4] cycloaddition of naphthalene-derived vinylcyclopropanes under visible-light irradiation and a proper triplet photosensitizer. The reaction affords dearomatized polycyclic molecules possessing a nine-membered-ring with an E-olefin moiety in good yields (up to 86%) and stereoselectivity (up to 8.8/1 E/Z). Detailed computational studies reveal the origin behind the favorable formation of the thermodynamically less stable isomers. Diverse derivations of the dearomatized products have also been demonstrated.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. The synthesis of medium-sized-ring molecules containing Z/E-olefins via dearomative cycloaddition reactions.
a. Selected natural products with medium-sized-rings containing an E-olefin. b. UV promoted dearomative cycloadditions of benzene-derived VCP. c. Energy transfer enabled dearomative cycloadditions of naphthalene-derives. d. Synthesis of medium-sized-rings containing an E-olefin via dearomative cycloaddition (This work).
Fig. 2
Fig. 2. The photosensitizers used in this study.
The triplet energies of photosensitizers are cited from ref. .
Fig. 3
Fig. 3. Substrate Scope.
Reaction conditions: 1 (0.2 mmol) and Ir(ppy)3 (1 mol%) in DCM (2 mL) were irradiated by blue LEDs (24 W, 455 nm) at room temperature under argon for 24 h. The E/Z ratios of 2 were determined by 1H NMR spectrum of the crude reaction mixture. Isolated yields of E-2 are reported. Note: (a) Combined yield of E-2j and Z-2j.
Fig. 4
Fig. 4. Energy profile of the dearomative [5 + 4] cycloaddition reaction of naphthalene-derived VCP.
Calculated at the (U)M062X-D3/def2-TZVPP (SMD, DCM)//(U)B3LYP-D3(BJ)/def2-SVP (SMD, DCM) level of theory. The Gibbs free energies (ΔG) are in kcal mol–1. The values in brown are bond distances (in Å), and the underlined values are Mulliken spin populations at specified atoms.
Fig. 5
Fig. 5
Diverse transformations further building-up molecular complexity.
See this image and copyright information in PMC

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