Photocatalytic Intramolecular Allyl Migration of Silyl Enol Ethers

Abstract

A photocatalytic platform for allylic α-alkylation of carbonyl compounds through intramolecular oxidative allyl migration is developed. This metal-free protocol enables precise allyl assembly under mild conditions with high efficiency and broad substrate scope, encompassing the tolerance of the challenging quaternary carbon center and internal olefin derivatives. Mechanistic investigations reveal a radical-mediated cyclization pathway.

Keywords

Photo-induced electron transfer - Organic photocatalyst - Enol silyl ether - α-alkylation - 7-Endo-trig cyclization

Publikationsverlauf

Eingereicht: 05. Mai 2025

Angenommen nach Revision: 30. Mai 2025

Accepted Manuscript online:
30. Mai 2025

Artikel online veröffentlicht:
24. Juli 2025

• References

• 1 Pitre SP, Overman LE. Chem Rev 2022; 122: 1717
• 2a Cao W, Wang Z, Hao Y, Wang T, Fu S, Liu B. Angew Chem Int Ed 2023; 62: e202305516
• 2b Tu C, Yang Y, Jiang Y. et al. Angew Chem Int Ed 2024; 63: e202409997
• 2c Zhou C, Qin W, Tu C, Chen Y, Fu S, Liu B. Angew Chem Int Ed 2025; e202503943
• 3 Choi JW, Kim GJ, Kim HJ. et al. Bioorg Chem 2020; 105: 104434
• 4 Motohashi K, Sue M, Furihata K, Ito S, Seto H. J Nat Prod 2008; 71: 595
• 5 Ryu M-J, Hwang S, Kim S. et al. Org Lett 2019; 21: 5779
• 6 Wang Z, Zhao S-M, Hu Y-Y. et al. Phytochemistry 2018; 145: 153
• 7a For selected base-promoted allylic α-alkylation of carbonyl compounds, see. Li M-M, Zhang T, Cheng L. et al. Nat Commun 2023; 14: 3326
• 7b For review, see. Cano R, Zakarian A, McGlacken GP. Angew Chem Int Ed 2017; 56: 9278
• 8a For selected Claisen rearrangement to synthesize allylic α-alkylation of carbonyl compounds, see. Geherty ME, Dura RD, Nelson SG. J Am Chem Soc 2010; 132: 11875
• 8b Ketcham JM, Biannic B, Aponick AT. Chem Commun 2013; 49: 4157
• 8c Padmanaban M, Carvalho LCR, Petkova D. et al. Tetrahedron 2015; 71: 5994
• 8d Williams CG, Nistanaki SK, Dong K, Lee W, Houk KN, Nelson HM. Org Lett 2024; 26: 4847
• 8e For review, see. Martín Castro AM. Chem Rev 2004; 104: 2939
• 8f Liu Y-B, Liu X-H, Feng X-M. Chem Sci 2022; 13: 12290
• 9a For selected transition-metal-catalyzed allylic allylation, see. Yu F-L, Bai D-C, Liu X-Y. et al. ACS Catal 2018; 8: 3317
• 9b Zhai M, Zhang J, Tao Z. Org Lett 2025; 27: 2358
• 9c For review, see. Kazmaier U. Org Chem Front 2016; 3: 1541
• 9d Junk L, Kazmaier U. ChemistryOpen 2020; 9: 929
• 10a For selected oxidative allylation to synthesize allylic α-alkylation of carbonyl compounds, see. Fujii T, Hirao T, Ohshiro Y. Tetrahedron Lett 1992; 33: 5823
• 10b Hirao T, Fujii T, Ohshiro Y. Tetrahedron 1994; 50: 10207
• 10c Hwu JR, Chen CN, Shiao S-S. J Org Chem 1995; 60: 856
• 10d Hirao T, Sakaguchi M, Ishikawa T, Ikeda I. Synth Commun 1995; 25: 2579
• 10e Hwu JR, Shiao S-S, Hakimelahi GH. Appl Organomet Chem 1997; 11: 381
• 10f Zhang Y, Raines AJ, Flowers RA. Org Lett 2003; 5: 2363
• 10g Zhang Y, Raines AJ, Flowers II RA. J Org Chem 2004; 69: 6267
• 10h Devery III JJ, Mohanta PK, Casey BM, Flowers III RA. Synlett 2009; 2009: 1490
• 10i Konkol LC, Jones BT, Thomson RJ. Org Lett 2009; 11: 5550
• 11a For selected photocatalytic strategies to synthesize allylic α-alkylation of carbonyl compounds, see. Gontala A, Jang GS, Woo SK. Bull Korean Chem Soc 2021; 42: 506
• 11b Qu W-Y, Zhou X-S, Xiao W-J, Chen J-R. Sci China Chem 2024; 67: 3807
• 11c Tan X, Song Z, Liang X. et al. Org Lett 2024; 26: 5403
• 12a Hu M, Cao W, Wang Z. et al. Chin J Chem 2023; 41: 2502
• 12b Du J, Fu S, Liu B. Org Lett 2024; 26: 4721
• 13 General procedure for the photocatalytic reactions: Under an air atmosphere, a 25.0 mL reaction test tube was charged with silyl enol ether 1 (0.05 mmol, 1.0 equiv), Mes-Acr⁺BF₄ ⁻ (5 mol%), and freshly distilled MeCN (5 mL). After removing the air balloon, the reaction was carried out under illumination from two 430-nm blue LED lights with vigorous stirring, and a fan was used to dissipate the heat from the lights. After stirring at rt for 2–5 min, the resulting mixture was concentrated under reduced pressure, and the residue was purified by flash chromatography on silica gel to give the product 2.
• 14 For conformational analysis of the relative stereochemistry about compound 2x, see Supporting Information.
• 15a For selected iridium-catalyzed branch-selective allylation reactions. He H, Zheng X-J, Li Y, Dai L-X, You S-L. Org Lett 2007; 9: 4339
• 15b Chen W-Y, Chen M, Hartwig JF. J Am Chem Soc 2014; 136: 15825
• 15c Jiang X-Y, Chen W-Y, Hartwig JF. Angew Chem Int Ed 2016; 55: 5819
• 15d Huo X-H, He R, Zhang X, Zhang W-B. J Am Chem Soc 2016; 138: 11093
• 15e Hethcox C, Shockley SE, Stoltz BM. Angew Chem Int Ed 2016; 55: 16092
• 16a For selected Claisen rearrangement-mediated branch-selective allylation reactions. Vanderbaan JL, Bickelhaupt F. Tetrahedron Lett 1986; 27: 6267
• 16b Sugiura M, Nakai T. Tetrahedron Lett 1987; 28: 5879
• 16c Sugiura M, Yanagisawa M, Nakai T. Synlett 1995; 5: 447
• 17 For the structure of the starting material corresponding to compound 2y, see page S29 of Supporting Information.
• 18 For detailed elucidation of reactivity disparities between benzannulated and non-benzannulated silyl enol ethers, see Supporting Information.
• 19 For other substrates that failed to yield the corresponding target products, see Supporting Information.
• 20 For HRMS of TEMPO/BHT-trapped product, see Supporting Information.
• 21 For HRMS result of the reaction with radical scavenger 1,1-diphenylethylene under standard condition, see Supporting Information.
• 22 For the test of amount of water in solvent, see Supporting Information.
• 23 For HRMS of silanols, see Supporting Information.