Photoredox-catalyzed four-atom skeletal editing of 1,3-diketones with alkenes and aldehydes

doi:10.1016/S1872-2067(25)64863-7

Abstract

Abstract:

Cleavage and reassembly of C-C bonds is a fascinating and challenging strategy to forge complex high-value molecules in an atom- and step-efficient manner. Herein, we disclose a photoredox-catalyzed four-atom skeletal editing strategy, enabling highly selective reassembly of 1,3-diketones into architecturally distinct acylated 1,5-ketoalcohols with excellent atom, step, and redox economy. Notably, this propoxy insertion unit (i.e., three sp³-hybridized carbons and one oxygen atom) is derived from the other two simple and readily available starting materials (i.e., alkene and aldehyde). Experimental studies have elucidated the key intermediate (lactol) and reaction mechanism (radical-radical crossover cyclization/rearrangement), which are distinct from classical De Mayo reaction. More importantly, the rapid construction of high-value-added product γ,δ-unsaturated ketones and dihydropyrans is also achieved via photocatalytic synthesis of acylated 1,5-ketoalcohols/Lewis acid-promoted Wagner-Meerwein rearrangement cascade and photocatalytic formal [2+2+2] annulation/MsCl-promoted elimination cascade, respectively.

Key words: C-C bond cleavage, 1,3-Diketones, Photoredox catalysis, 1,5-Ketoalcohols, Alkenes, Aldehydes

Wei Wang, Bin Chen, Ting Li, Zhengchu Chen, Lei Yuan, Qiang Fu, Siping Wei, Xiao-Feng Wu, Dong Yi. Photoredox-catalyzed four-atom skeletal editing of 1,3-diketones with alkenes and aldehydes[J]. Chinese Journal of Catalysis, 2026, 82: 212-224.

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URL: https://www.cjcatal.com/EN/10.1016/S1872-2067(25)64863-7

https://www.cjcatal.com/EN/Y2026/V82/I3/212

Figures/Tables 6

Fig. 1. Catalytic skeletal editing strategies of 1,3-diketones.

Fig. 2. Optimization of the reaction conditions a,b. a Reaction conditions: 1 (0.15 mmol), 2 (0.15 mmol), 3 (0.1 mmol), Ir(p-F-ppy)3 (1 mol%), K3PO4 (10 mol%), DMF (1 mL), 30 W blue LEDs, argon atmosphere, r.t., 6 h. n.d. = not detected. bThe yield was determined by 1H NMR using 1,3,5-trimethoxybenzene as an internal standard. cIsolated yields based on 3.

Fig. 3. Substrate scope investigation a. Reaction conditions: a aldehyde (0.45 mmol), styrene (0.45 mmol), 1,3-diketone (0.3 mmol), Ir(p-F-ppy)3 (1 mol%), K3PO4 (10 mol%), DMF (3 mL), 30 W blue LEDs, argon atmosphere, r.t., 6 h, in a sealed tube. b 3DPA2FBN instead of Ir(p-F-ppy)3. c K3PO4 (30 mol%). d fac-Ir(ppy)3 instead of Ir(p-F-ppy)3. e [Ir(dtbbpy)(ppy)2)]PF6 instead of Ir(p-F-ppy)3. f 4CzIPN instead of Ir(p-F-ppy)3. g NaOH instead of K3PO4.

Fig. 4. Late-stage derivatization of biologically relevant molecules. Reaction conditions: aldehyde (0.45 mmol), 1,1-diphenylethylene (0.45 mmol), acetylacetone (0.3 mmol), Ir(p-F-ppy)3 (1 mol%), K3PO4 (10 mol%), DMF (3 mL), 30 W blue LEDs, argon atmosphere, r.t., 6 h, in a sealed tube.

Fig. 5. Mechanistic investigations. (A) Radical inhibition experiment with a radical scavenger (TEMPO, DMPO, or DNB). (B) Radical-probing experiment I with (1-(2-phenylcyclopropyl)vinyl)benzene instead of 1,1-diphenylethylene 2. (C) Radical-probing experiment II with N-methylquinoxalin-2(1H)-one instead of 1,1-diphenylethylene 2. (D) Radical-probing experiment III with the addition of allyl sulfone. (E) UV-visible absorption spectrum. (F) Stern-Volmer quenching experiment. (G) Cyclic voltammetry measurement. (H) Photocatalyst evaluation with different triplet stale energies. (I) In situ 1H-NMR experiment. (J) Mechanistic proposal.

Fig. 6. Synthetic utility of the methodology. (A) Photocatalytic formal [2+2+2] annulation for synthesis of dihydropyrans. (B) Scale-up reaction and stream-down modifications. (C) Synthesis of γ,δ-unsaturated ketones via sequential rearrangements. aTsOH·H2O, MeOH, r.t. b Ph3PCH3Br, KOtBu, THF, 0 °C to r.t. c NBS, TsOH, DCM, r.t. d NaBH4, MeOH, 0 °C to r.t. e LiAlH4, THF, 0 °C to r.t. f MeOH/KOH, DMP, CH2Cl2, r.t. g NaOAc, NH2OH·HCl, MeOH, r.t. h TfOH, m-CPBA, CH2Cl2, r.t.

References

[1]	D. Ba, S. Wen, Q. Tian, Y. Chen, W. Lv, G. Cheng, Nat. Commun., 2020, 11, 4219.
[2]	L. Li, W. Huang, L. Chen, J. Dong, X. Ma, Y. Peng, Angew. Chem. Int. Ed., 2017, 56, 10539-10544.
[3]	H.-J. Miao, J.-H. Zhang, W. Li, W. Yang, H. Xin, P. Gao, X.-H. Duan, L.-N. Guo, Chem. Sci., 2024, 15, 8993-8999.
[4]	T. Shen, Y. Zhang, Y.-F. Liang, N. Jiao, J. Am. Chem. Soc., 2016, 138, 13147-13150.
[5]	M. M. Shoshani, S. A. Johnson, Nat. Chem., 2017, 9, 1282-1285.
[6]	Q. Wang, X. Yao, P. Zhao, W. Liu, W. Zhao, X. Fang, Y. Zhu, G. Dai, J. Org. Chem., 2023, 88, 14193-14199.
[7]	X. Wu, C. Zhu, Chin. J. Chem., 2019, 37, 171-182.
[8]	G. Fumagalli, S. Stanton, J. F. Bower, Chem. Rev., 2017, 117, 9404-9432.
[9]	D.-S. Kim, W.-J. Park, C.-H. Jun, Chem. Rev., 2017, 117, 8977-9015.
[10]	L. Souillart, N. Cramer, Chem. Rev., 2015, 115, 9410-9464.
[11]	B. W. Joynson, L. T. Ball, Helv. Chim. Acta, 2023, 106, e202200182.
[12]	S. F. Kim, C. Amber, G. L. Bartholomew, R. Sarpong, Acc. Chem. Res., 2025, 58, 1786-1800.
[13]	Z. Liu, P. Sivaguru, Y. Ning, Y. Wu, X. Bi, Chem., 2023, 29, e202301227.
[14]	F.-P. Wu, J. L. Tyler, C. G. Daniliuc, F. Glorius, ACS Catal., 2024, 14, 13343-13351.
[15]	P. Xu, A. Studer, Acc. Chem. Res., 2025, 58, 647-658.
[16]	B. D. Challand, H. Hikino, G. Kornis, G. Lange, P. De Mayo, J. Org. Chem., 1969, 34, 794-806.
[17]	P. De Mayo, H. Takeshita, Can. J. Chem., 1963, 41, 440-449.
[18]	R. Martinez-Haya, L. Marzo, B. König, Chem. Commun., 2018, 54, 11602-11605.
[19]	T. O. Paulisch, L. A. Mai, F. Strieth-Kalthoff, M. J. James, C. Henkel, D. M. Guldi, F. Glorius, Angew. Chem. Int. Ed., 2022, 61, e202112695.
[20]	W. Zhang, S. Luo, Chem. Commun., 2022, 58, 12979-12982.
[21]	X. Sun, Y. Liu, Y. Yin, X. Ban, X. Zhao, Z. Jiang, Nat. Chem., 2024, 16, 1169-1176.
[22]	Z. Liu, P. Sivaguru, G. Zanoni, E. A. Anderson, X. Bi, Angew. Chem. Int. Ed., 2018, 57, 8927-8931.
[23]	Y. Wu, Y. Ning, X. Han, P. Liao, Y. Xia, P. Sivaguru, X. Bi, Org. Lett., 2022, 24, 8136-8141.
[24]	Y.-Y. Ren, M. Chen, K. Li, S.-F. Zhu, Chem. Asian J., 2018, 13, 2606-2610.
[25]	H. Zhang, Z. Wang, Z. Wang, Y. Chu, S. Wang, X.-P. Hui, ACS Catal., 2022, 12, 5510-5516.
[26]	S. Li, C. Zhang, G. Pan, L. Yang, Z. Su, X. Feng, X. Liu, ACS Catal., 2023, 13, 4656-4666.
[27]	D. Ba, G. Cheng, Chin. J. Org. Chem., 2022, 42, 2888-2897.
[28]	D. Ba, S. Wen, Q. Y. Tian, Y. H. Chen, W. W. Lv, G. L. Cheng, Nat. Commun., 2020, 11, 4219.
[29]	M. Roudier, T. Constantieux, A. Quintard, J. Rodriguez, Org. Lett., 2014, 16, 2802-2805.
[30]	M. Roudier, T. Constantieux, A. Quintard, J. Rodriguez, ACS Catal., 2016, 6, 5236-5244.
[31]	W. Wei, S. Cherukupalli, L. Jing, X. Liu, P. Zhan, Drug Discov. Today, 2020, 25, 1839-1845.
[32]	K. Sota, M. Mitsukuchi, J. Nakagami, Y. Tachi, J. Sawada, S. Otomo, M. Ohzeki, Yakugaku Zasshi, 1982, 102, 365-370.
[33]	S. Costa, F. Zappaterra, D. Summa, B. Semeraro, G. Fantin, Molecules, 2020, 25, 2192.
[34]	C. Liang, D. Tian, Y. Liu, H. Li, J. Zhu, M. Li, M. Xin, J. Xia, Eur. J. Med. Chem., 2019, 174, 130-141.
[35]	Y. Li, G. Li, C. Zuo, X. Wang, F. Han, Y. Jia, H. Shang, Y. Tian, Eur. J. Med. Chem., 2024, 270, 116367.
[36]	M. Yamashita, A. Nakanishi, C. Chang, K. Tsurushima, K. Nakamoto, A. Iida, Chem. Pharm. Bull., 2024, 72, 693-699.
[37]	X. Qi, M. Li, X.-M. Zhang, X.-F. Dai, J. Cui, D.-H. Li, Q.-Q. Gu, Z.-H. Lv, J. Li, Molecules, 2020, 25, 2306.
[38]	Z. Cao, W. Zheng, M. Huang, X. Yao, W. Zhu, L. Sheng, Z. Pan, Y. Bian, T. Zhang, C. Zhu, Med. Chem., 2023, 19, 586-593.
[39]	C. Bian, J. Zhang, X. Zheng, M. Qiao, Y. Li, X. Chen, S. Si, Eur. J. Med. Chem., 2024, 267, 116181.
[40]	U. Mrowietz, Eur. J. Dermatol., 1999, 9, 346-351.
[41]	H. H. Sigurdsson, P. Jansook, T. Loftsson, J. Drug Deliv. Sci. Technol., 2024, 101, 106207.
[42]	Y.-Z. Tang, Y.-H. Liu, J.-X. Chen, Mini Rev. Med. Chem., 2012, 12, 53-61.
[43]	I. Dreier, L. H. Hansen, P. Nielsen, B. Vester, Bioorg. Med. Chem. Lett., 2014, 24, 1043-1046.
[44]	N. Alvarenga, S. E. Payer, P. Petermeier, C. Kohlfuerst, A. L. Meleiro Porto, J. H. Schrittwieser, W. Kroutil, ACS Catal., 2020, 10, 1607-1620.
[45]	R. Guo, G. Zhang, J. Am. Chem. Soc., 2017, 139, 12891-12894.
[46]	N. Khamis, Y. Zheng, M. N. Diamantakis, G. J. Clarkson, J. Liu, M. Wills, J. Org. Chem., 2024, 89, 2759-2763.
[47]	F. Lagasse, M. Tsukamoto, C. J. Welch, H. B. Kagan, J. Am. Chem. Soc., 2003, 125, 7490-7491.
[48]	A. V. Lozanova, A. V. Stepanov, V. V. Veselovsky, Russ. Chem. Bull., 2005, 54, 1254-1257.
[49]	C. C. Aldrich, L. Venkatraman, D. H. Sherman, R. A. Fecik, J. Am. Chem. Soc., 2005, 127, 8910-8911.
[50]	F. Becerril-Jiménez, D. E. Ward, Org. Lett., 2012, 14, 1648-1651.
[51]	G. E. Beye, D. E. Ward, J. Am. Chem. Soc., 2010, 132, 7210-7215.
[52]	R. Nakamura, K. Tanino, M. Miyashita, Org. Lett., 2003, 5, 3583-3586.
[53]	M. Shimizu, K. Shimono, T. Hiyama, Chem.Asian J., 2007, 2, 1142-1149.
[54]	S. Sun, Y. Yang, R. Zhao, D. Zhang, L. Liu, J. Am. Chem. Soc., 2020, 142, 19346-19353.
[55]	V. J. A. Jameson, H. M. Cochemé, A. Logan, L. R. Hanton, R. A. J. Smith, M. P. Murphy, Tetrahedron, 2015, 71, 8444-8453.
[56]	S. Liang, J. Jasinski, G. B. Hammond, B. Xu, Org. Lett., 2015, 17, 162-165.
[57]	M. Nishizawa, M. Skwarczynski, H. Imagawa, T. Sugihara, Chem. Lett., 2002, 31, 12-13.
[58]	Y. L. Xing, G. A. O'Doherty, ChemistrySelect, 2022, 7, e202200266.
[59]	B. Liu, F. Jin, T. Wang, X. Yuan, W. Han, Angew. Chem. Int. Ed., 2017, 56, 12712-12717.
[60]	B. B. Liu, W. Han, Synlett, 2018, 29, 383-387.
[61]	D. A. Chaudhari, R. A. Fernandes, J. Org. Chem., 2016, 81, 2113-2121.
[62]	A. Matsumoto, N. Maeda, K. Maruoka, J. Am. Chem. Soc., 2023, 145, 20344-20354.
[63]	L. Leng, J. M. Ready, ACS Catal., 2021, 11, 13714-13720.
[64]	B. Bieszczad, S. Z. Zard, Org. Lett., 2022, 24, 6973-6977.
[65]	S. Sisti, M. Galeotti, F. Scarchilli, M. Salamone, M. Costas, M. Bietti, J. Am. Chem. Soc., 2023, 145, 22086-22096.
[66]	Y. Jiang, S. Chen, Y. Chen, A. Gu, C. Tang, J. Am. Chem. Soc., 2024, 146, 2769-2778.
[67]	X.-M. Chen, L. Song, J. Pan, F. Zeng, Y. Xie, W. Wei, D. Yi, Chin. Chem. Lett., 2024, 35, 110112.
[68]	Q. Feng, J. Hao, Y. Hu, R. Fu, W. Wei, D. Yi, Chin. Chem. Lett., 2025, 36, 110582.
[69]	T. Li, W. Wang, M. Dong, Z. Zhang, S. Yu, Z. Chen, S. Wei, D. Yi, Chin. J. Chem., 2024, 42, 957-962.
[70]	W. Li, L. Tan, Y. Chen, R. Liu, Z. Qi, S. Yuan, Z. Huang, S. Wei, X. Du, D. Yi, Chin. J. Chem., 2024, 42, 157-163.
[71]	Y. Lv, H. Ding, J. You, W. Wei, D. Yi, Chin. Chem. Lett., 2024, 35, 109107.
[72]	T. Zou, Y. He, R. Liu, Y. Zhang, S. Wei, J. Lu, J. Wang, L. Wang, Q. Fu, D. Yi, Chin. Chem. Lett., 2023, 34, 107822.
[73]	K.-G. Cao, T.-Y. Gao, L.-L. Liao, C.-K. Ran, Y.-X. Jiang, W. Zhang, Q. Zhou, J.-H. Ye, Y. Lan, D.-G. Yu, Chin. J. Catal., 2024, 56, 74-80.
[74]	K. Jing, M.-K. Wei, S.-S. Yan, L.-L. Liao, Y.-N. Niu, S.-P. Luo, B. Yu, D.-G. Yu, Chin. J. Catal., 2022, 43, 1667-1673.
[75]	T. Ju, Q. Fu, J.-H. Ye, Z. Zhang, L.-L. Liao, S.-S. Yan, X.-Y. Tian, S.-P. Luo, J. Li, D.-G. Yu, Angew. Chem. Int. Ed., 2018, 57, 13897-13901.
[76]	T. Ju, Y.-Q. Zhou, K.-G. Cao, Q. Fu, J.-H. Ye, G.-Q. Sun, X.-F. Liu, L. Chen, L.-L. Liao, D.-G. Yu, Nat. Catal., 2021, 4, 304-311.
[77]	L.-L. Liao, G.-M. Cao, Y.-X. Jiang, X.-H. Jin, X.-L. Hu, J. J. Chruma, G.-Q. Sun, Y.-Y. Gui, D.-G. Yu, J. Am. Chem. Soc., 2021, 143, 2812-2821.
[78]	L.-L. Liao, G.-M. Cao, J.-H. Ye, G.-Q. Sun, W.-J. Zhou, Y.-Y. Gui, S.-S. Yan, G. Shen, D.-G. Yu, J. Am. Chem. Soc., 2018, 140, 17338-17342.
[79]	L. Song, D.-M. Fu, L. Chen, Y.-X. Jiang, J.-H. Ye, L. Zhu, Y. Lan, Q. Fu, D.-G. Yu, Angew. Chem. Int. Ed., 2020, 59, 21121-21128.
[80]	H.-Z. Xiao, B. Yu, S.-S. Yan, W. Zhang, X.-X. Li, Y. Bao, S.-P. Luo, J.-H. Ye, D.-G. Yu, Chin. J. Catal., 2023, 50, 222-228.
[81]	E. Fava, A. Millet, M. Nakajima, S. Loescher, M. Rueping, Angew. Chem. Int. Ed., 2016, 55, 6776-6779.
[82]	F. Li, D. Tian, Y. Fan, R. Lee, G. Lu, Y. Yin, B. Qiao, X. Zhao, Z. Xiao, Z. Jiang, Nat. Commun., 2019, 10, 1774.
[83]	Z. Liu, X. Nan, T. Lei, C. Zhou, Y. Wang, W. Liu, B. Chen, C. Tung, L. Wu, Chin. J. Catal., 2018, 39, 487-494.
[84]	K. Ota, K. Nagao, H. Ohmiya, Org. Lett., 2021, 23, 4420-4425.
[85]	S. Pan, M. Jiang, J. Hu, R. Xu, X. Zeng, G. Zhong, Green Chem., 2020, 22, 336-341.
[86]	C. Wang, J. Qin, X. Shen, R. Riedel, K. Harms, E. Meggers, Angew. Chem. Int. Ed., 2016, 55, 685-688.
[87]	H.-M. Huang, P. Bellotti, F. Glorius, Acc. Chem. Res., 2022, 55, 1135-1147.
[88]	B. Jin, A. Gopalsamy, B. Peng, L. Sha, S. Tentarelli, L. Gingipalli, J. Org. Chem., 2023, 88, 1327-1330.
[89]	X. Peng, Y. Hirao, S. Yabu, H. Sato, M. Higashi, T. Akai, S. Masaoka, H. Mitsunuma, M. Kanai, J. Org. Chem., 2023, 88, 6333-6346.
[90]	L. Pitzer, F. Sandfort, F. Strieth-Kalthoff, F. Glorius, J. Am. Chem. Soc., 2017, 139, 13652-13655.
[91]	H. Yu, T. Zhan, Y. Zhou, L. Chen, X. Liu, X. Feng, ACS Catal., 2022, 12, 5136-5144.
[92]	Z. Liu, C. Zhou, T. Lei, X.-L. Nan, B. Chen, C.-H. Tung, L.-Z. Wu, CCS Chem., 2020, 2, 582-588.
[93]	T. Han, S. Zhang, J. Li, Q. Mou, J. Gao, B. Cao, C.-J. Li, M. Liu, Green Chem., 2025, 27, 7600-7607.
[94]	F. Millward, E. Zysman-Colman, Angew. Chem. Int. Ed., 2024, 63, e202316169.
[95]	M. Nakajima, E. Fava, S. Loescher, Z. Jiang, M. Rueping, Angew. Chem. Int. Ed., 2015, 54, 8828-8832.
[96]	M. Gong, Q. Li, H. Qin, H. Fu, G. Li, Y. Li, Y. Wu, Chem. Commun., 2024, 60, 14664-14667.
[97]	R. Hojo, A. M. Polgar, Z. M. Hudson, ACS Sustainable Chem. Eng., 2022, 10, 9665-9678.
[98]	J.-C. Hou, J. Jiang, H. Dai, J.-S. Wang, T. Li, X. Chen, W.-M. He, Sci. China Chem., 2025, 68, 1945-1951.
[99]	Y. Yan, G. Li, J. Ma, C. Wang, J. Xiao, D. Xue, Green Chem., 2023, 25, 4129-4136.
[100]	A. Singh, K. Teegardin, M. Kelly, K. S. Prasad, S. Krishnan, J. D. Weaver, J. Organomet. Chem., 2015, 776, 51-59.
[101]	C. K. Prier, D. A. Rankic, D. W. C. MacMillan, Chem. Rev., 2013, 113, 5322-5363.
[102]	H. G. Roth, N. A. Romero, D. A. Nicewicz, Synlett, 2016, 27, 714-723.
[103]	J. Li, S. Wang, J. Zhao, P. Li, Org. Lett., 2022, 24, 5977-5981.
[104]	J. Liu, S. Tang, H. Xu, R. Zhang, J. Zhao, P. Zhang, P. Li, Org. Lett., 2022, 24, 9366-9369.
[105]	S. Tang, J. Liu, M. Zhang, D. Wang, Y. Wang, J. Zhao, P. Li, Org. Chem. Front., 2024, 11, 3160-3164.
[106]	F. Amemiya, K. Fuse, T. Fuchigami, M. Atobe, Chem. Commun., 2010, 46, 2730-2732.
[107]	D. Leifert, A. Studer, Angew. Chem. Int. Ed., 2020, 59, 74-108.
[108]	A. M. Armaly, Y. C. DePorre, E. J. Groso, P. S. Riehl, C. S. Schindler, Chem. Rev., 2015, 115, 9232-9276.
[109]	J. I. Bowen, X. Zhong, K. Gao, B. Reed, M. P. Crump, L. Wang, C. L. Willis, Chem. Sci., 2024, 15, 5319-5326.
[110]	F. J. Fuentes-Pantoja, A. Cordero-Vargas, Synthesis, 2021, 53, 4433-4439.
[111]	C.-Y. Tang, J. Wu, F.-T. Ji, F. Tian, L. Peng, L.-L. Wang, Org. Chem. Front., 2023, 11, 211-216.
[112]	A. Douchez, A. Geranurimi, W. D. Lubell, Acc. Chem. Res., 2018, 51, 2574-2588.
[113]	N. J. Line, B. P. Witherspoon, E. N. Hancock, M. K. Brown, J. Am. Chem. Soc., 2017, 139, 14392-14395.
[114]	M. D. McLeod, C. C. Waller, A. Esquivel, G. Balcells, R. Ventura, J. Segura, Ó. J. Pozo, Anal. Chem., 2017, 89, 1602-1609.
[115]	B. Zhang, J. Liu, D. Gao, X. Yu, J. Wang, X. Lei, Eur. J. Med. Chem., 2019, 182, 111672.
[116]	C. Zhao, J. Wang, Q. Xiao, Front. Med., 2021, 8, 647494.