Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Dec 30;15(1):10866.
doi: 10.1038/s41467-024-55110-3.

Aza-[4 + 2]-cycloaddition of benzocyclobutenones into isoquinolinone derivatives enabled by photoinduced regio-specific C-C bond cleavage

Liangkun Yang #  1 , Shiyang Li #  1 , Lichao Ning  1 , Hansen Zhao  1 , Liang Zhou  1 , Weidi Cao  2 , Xiaoming Feng  3
Affiliations

Aza-[4 + 2]-cycloaddition of benzocyclobutenones into isoquinolinone derivatives enabled by photoinduced regio-specific C-C bond cleavage

Liangkun Yang et al. Nat Commun. .

Abstract

The activation of C-C bond of benzocyclobutenones under mild reaction conditions remains a challenge. We herein report a photoinduced catalyst-free regio-specific C1-C8 bond cleavage of benzocyclobutenones, enabling the generation of versatile ortho-quinoid ketene methides for aza-[4 + 2]-cycloaddition with imines, which offers a facile route to isoquinolinone derivatives, including seven family members of protoberberine alkaloids, gusanlung A, B, D, 8-oxotetrahydroplamatine, tetrahydrothalifendine, tetrahydropalmatine, and xylopinine. Furthermore, the catalytic enantioselective version of this strategy is also realized by merging synergistic photocatalysis and chiral Lewis acid catalysis. Mechanistic studies provide compelling evidence to rationalize the photoisomerization/cycloaddition cascade process.

PubMed Disclaimer

Conflict of interest statement

Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. C−C bond cleavage of benzocyclobutenones and regio-selective aza-[4+2]-photocycloaddition with imines.
a Two strategies for C−C bond cleavage of BCBs. b This work: photoinduced regio-specific aza-[4+2]-photocycloaddition of BCBs and asymmetric version.
Fig. 2
Fig. 2. Substrate scope of cycloaddition of BCBs with 3,4-dihydroisoquinolines.
Conditions: A (0.1 mmol), B (0.1 mmol) in Et2O (1.0 mL) under N2 atmosphere and 5 W LED (λmax = 365 nm) irradiation at 10 °C, yield of isolated product. a10 W instead of 5 W. bAfter 12 h, another portion A (0.1 mmol) was added and reacted for further 12 h; c10 W LED in THF was used.
Fig. 3
Fig. 3. Substrate scope of asymmetric cycloaddition of BCBs and benzosulfonimides.
Conditions: A (2.0 equiv), D (0.1 mmol), Ni(NTf2)2/L3-PisEPh (1.2:1, 10 mol%) and 3 Å MS (25 mg) in CH2Cl2 (3.0 mL) at 10 °C under N2 atmosphere and irradiation (20 W LED, λmax = 365 nm). Yield of isolated product. Ee was determined by UPC2.
Fig. 4
Fig. 4. Synthetic application.
a Gram-scale synthesis. b Further transformations.
Fig. 5
Fig. 5. Mechanistic studies.
a Radical trapping experiments. b Control experiments. c Proposed mechanism and DFT calculation.
See this image and copyright information in PMC

References

    1. Chen, F., Wang, T. & Jiao, N. Recent advances in transition-metal-catalyzed functionalization of unstrained carbon–carbon bonds. Chem. Rev.114, 8613–8661 (2014). - PubMed
    1. Souillart, L. & Cramer, N. Catalytic C–C bond activations via oxidative addition to transition metals. Chem. Rev.115, 9410–9464 (2015). - PubMed
    1. Murakami, M. & Ishida, N. Potential of metal-catalyzed C–C single bond cleavage for organic synthesis. J. Am. Chem. Soc.138, 13759–13769 (2016). - PubMed
    1. Fumagalli, G., Stanton, S. & Bower, J. F. Recent methodologies that exploit C–C single-bond cleavage of strained ring systems by transition metal complexes. Chem. Rev.117, 9404–9432 (2017). - PubMed
    1. Kim, D.-S., Park, W.-J. & Jun, C.-H. Metal–organic cooperative catalysis in C–H and C–C bond activation. Chem. Rev.117, 8977–9015 (2017). - PubMed

LinkOut - more resources