Densely-Functionalized Bicyclic Cyclopentanones by Combined Photoinduced 6-endo-trig Giese Additions and Mild Aldol Cyclizations

Article Article scientifique Article Densely-Functionalized Bicyclic Cyclopentanones by Combined Photoinduced 6-endo-trig Giese Additions and Mild Aldol Cyclizations eng 2026 2026-01-26 author Vinas Julia 909993 author Sellet Nicolas 416923 Chimie organique groupe 7 (CHOR7) author Fabri Bibiana 0000-0003-3466-3120 947651 author Levitre Guillaume 930843 author de Aguirre Adiran 935526 author Poblador Bahamonde Amalia Isabel 797442 Département de chimie organique (CHIOR) author Besnard Céline 682138 Administration de la section de chimie (CHIAD) author Lacour Jérôme 0000-0001-6247-8059 99165 Département de chimie organique (CHIOR) 3021-3029 10.1039/D5QO01635E 2052-4110 http://pubs.rsc.org/en/Content/ArticleLanding/2026/QO/D5QO01635E Polycyclic scaffolds are central to numerous natural products and pharmaceuticals, motivating concise, stereocontrolled routes to their construction. We report a photoredox-enabled synthesis of trans-fused [n.3.0] bicyclic ketones (n = 4, 5, 10) from malonate-derived enol ethers. α-Brominated intermediates, formed by acylation with 2-bromo-2-methylpropanoyl bromide, undergo radical cyclization under two complementary conditions: (i) acridinium orange (AOH+) with Hantzsch ester (HE) at 455 nm, or (ii) photoexcited HE alone at 365 nm. Both modes trigger 6-endo-trig Giese addition, C–O bond fragmentation, and hydrogen-atom transfer to α-branched cyclic ketones that ring-close under mild Brønsted or Lewis acid activation to trans-fused products with exclusive junction control. Mechanistic studies (Stern–Volmer, UV–Vis, electrochemistry) support two activation pathways — AOH+* quenching by HE or direct HE excitation — each generating the same radical intermediates in fine. DFT calculations validate mechanistic pathways and regioselectivity in favor of a philicity matching of the electrophilic radical and the polar electron-rich enol ether. The method accommodates ring-size diversity, accesses trans-hydrindanone architectures, and outcompetes 5-exo-trig spirocyclization. Dewey 540 Swiss National Science Foundation Superstable Chiral Cations and Reactive Ylides for Synthesis, Catalysis and Optical Applications 207539 CH 36 Département de chimie organique 141 false 760 Groupe Lacour 1412 Groupe Laboratoire de Cristallographie https://yareta.unige.ch/archives/aad79a5b-b1f6-426c-87af-1bd7272ef6b8 Organic chemistry frontiers 13 1e3633d5-6d70-407f-a5e1-6d6062086320 Article (Published version) Public OrgChemFront_2026_13_3021_6endoTrig.pdf 3587996 application/pdf CC BY-4.0 ec66d4248ffd59cd3d9e6e35210a4578921e631c7c4c0ca13ab50d6b92edcdca Vignette Public TOC.jpg 131957 image/png openAccess Faculté des sciences / Section de chimie et biochimie / Département de chimie organique

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Densely-Functionalized Bicyclic Cyclopentanones by Combined Photoinduced 6-endo-trig Giese Additions and Mild Aldol Cyclizations	Organic chemistry frontiers			2026	40	158

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Sellet, Nicolas